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Functional Smart
Nanomaterials and
Their Theranostics
Approaches
Alle Madhusudhan · Shiv Dutt Purohit ·
Rajendra Prasad · Azamal Husen Editors
Smart Nanomaterials Technology

Smart Nanomaterials Technology
Series Editors
Azamal Husen
, Department of Biotechnology, Smt. S. S. Patel Nootan Science &
Commerce College, Sankalchand Patel University, Visnagar, Gujarat, India
Department of Biotechnology, Graphic Era (Deemed to be University),
Dehradun, Uttarakhand, India
Laboratory of Bio Resource Management, Institute of Tropical Forestry and
Forest Product, University Putra Malaysia, UPM Serdang, Selangor, Malaysia
Mohammad Jawaid, Laboratory of Biocomposite Technology, Universiti Putra
Malaysia, INTROP, Serdang, Selangor, Malaysia

Nanotechnology is a rapidly growing scientiﬁc ﬁeld and has attracted a great interest
over the last few years because of its abundant applications in different ﬁelds like
biology, physics and chemistry. This science deals with the production of minute
particles called nanomaterials having dimensions between 1 and 100 nm which may
serve as building blocks for various physical and biological systems. On the other
hand, there is the class of smart materials where the material that can stimuli by
external factors and results a new kind of functional properties. The combination of
these two classes forms a new class of smart nanomaterials, which produces unique
functional material properties and a great opportunity to larger span of applica-
tion. Smart nanomaterials have been employed by researchers to use it effectively in
agricultural production, soil improvement, disease management, energy and environ-
ment, medical science, pharmaceuticals, engineering, food, animal husbandry and
forestry sectors.
This book series in Smart Nanomaterials Technology aims to comprehensively
cover topics in the fabrication, synthesis and application of these materials for applications in the following ﬁelds:
•Energy Systems—Renewable energy, energy storage (supercapacitors and elec- trochemical cells), hydrogen storage, photocatalytic water splitting for hydrogen
production
•Biomedical—controlled release of drugs, treatment of various diseases, biosen- sors,
•Agricultural—agricultural production, soil improvement, disease management, animal feed, egg, milk and meat production/processing,
•Forestry—wood preservation, protection, disease management
•Environment—wastewater treatment, separation of hazardous contaminants from wastewater, indoor air ﬁlters

Alle Madhusudhan
Rajendra Prasad
Editors
Functional Smart
Nanomaterials and Their
Theranostics Approaches

Editors
Alle Madhusudhan
Department of Chemistry
The University of Memphis
Memphis, TN, USA
Rajendra Prasad
School of Biochemical Engineering Indian Institute of Technology (BHU) Varanasi, Uttar Pradesh, India
Shiv Dutt Purohit
School of Chemical Engineering Yeungnam University Gyeongsan, Korea (Republic of)
Azamal Husen
Department of Biotechnology Smt. S. S. Patel Nootan Science & Commerce College, Sankalchand Patel University Visnagar, Gujarat, India
Department of Biotechnology Graphic Era (Deemed to be University) Dehradun, Uttarakhand, India
Laboratory of Bio Resource Management Institute of Tropical Forestry and Forest Product, University Putra Malaysia UPM Serdang, Selangor, Malaysia
ISSN 3004-8273 ISSN 3004-8281 (electronic)
Smart Nanomaterials Technology
ISBN 978-981-99-6596-0 ISBN 978-981-99-6597-7 (eBook)
https://doi.org/10.1007/978-981-99-6597-7
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Singapore Pte Ltd. 2024
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, speciﬁcally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microﬁlms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar
or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speciﬁc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional
claims in published maps and institutional afﬁliations.
This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721,
Singapore
Paper in this product is recyclable.

Preface
In recent years, nanotechnology has become an epoch-making area with enormous
potential and can revolutionize every aspect of our lives. One of the most inter-
esting applications of nanotechnology is the development of functional intelligent
nanomaterials, which interact with nano-class biological systems with remarkable
capabilities. These data will open a new era of medical care by increasing the space
for the development of diagnosis, treatment, and customized medical care.
The book
explores their potential in the ﬁeld of nanotechnology, which combines therapy and diagnosis, to explore the fascinating world of nanomaterials and realize accurate and personalized treatment strategies. This book outlines the latest development and
future prospects of functional intelligent nanomaterials in the medical ﬁeld with the contribution of leading researchers and experts in this ﬁeld.
This book is divided into 14 chapters and focuses on the speciﬁc aspects and
applications of functional intelligent nanomaterials. Chapters “Basic Principles
of Functional Materials for Biomedical Applications” and “Functional Biomaterials
for Targeted Drug Delivery Applications” introduce the basic principles of functional
materials, outline the unique characteristics of nanomaterials, and make them ideal candidates for biomedical applications and drug delivery applications. These chap- ters highlight the importance of exploring various materials and their manufacturing
techniques. Chapters “
Metallic Nanoparticles for Imaging and Therapy” and “Ther-
anostic Applications of Functional Nanomaterials Using Microscopic and Spectro- scopic Techniques
” comprise the information related to nanoparticles and their appli-
cations in the imaging and spectroscopy-based theranostic applications. After that, Chaps. “
Next-Generation Therapies for Breast Cancer”–“Functional Biomaterials
for Image-Guided Therapeutics of Solid Tumor” provide insights into the application
of functional nanomaterials in diagnosis and treatment of the cancer.
Chapters “Nanostructured Electrodes as Electrochemical Biosensors for Biomed-
ical Applications”to“Screen-Printed Electrode (SPE)-Based Biosensor
for Point-Of-Care (POC) Diagnostic in Medical Applications, Their Scope, and Challenges
” emphasize the role and signiﬁcance of the use of nanostructures
for biosensor-based theranostics applications. The development in biosensor-based
v

vi Preface
diagnostics for bacterial diseases has been also explained (Chap. “Development
in
Biosensor-Based Diagnostics for Bacterial Diseases: Opportunities and Chal-
lenges”). The sensing applications range from electrochemical biosensors, screen
printed
electrode-based point-of-care devices to the organ on chip systems. Finally,
the book provides insights into the next generations of therapy for various applica-
tions including type 2 diabetes mellitus using natural products, quantum dots, and
nanomaterials (Chaps. “Next-Generation Therapies for Type 2 Diabetes Mellitus”
and
“Quantum Dots for Theranostic Applications”).
The ultimate goal of this book is to provide comprehensive resources to
researchers,
students, and experts in nanotechnology and biomedical ﬁelds to empha-
size the potential and importance of functional intelligent nanomaterials in nanotech-
nology. The text aims to deepen understanding of the principles and applications of
these materials and to encourage further research and innovation in this interesting
and rapidly evolving ﬁeld.
We sincerely thank all authors for their contribution to the expertise and knowledge
of
this book. Their valuable insight and groundbreaking research enabled publica-
tions. Furthermore, we would like to thank the reviewers for their thoughtful opinions
and suggestions.
We hope this book will be a valuable resource for readers who want to explore
the
state-of-the-art development of functional smart nanomaterials and their rational
methods. We hope to contribute to improving the level of medical service and quality
of life by providing new ways of thinking, cooperation, and innovation to the global
public.
Memphis, USA
Gyeongsan, Korea (Republic of)
Varanasi, India
Visnagar, India
Alle Madhusudhan
Shiv Dutt Purohit
Rajendra Prasad
Azamal Husen

Contents
Basic Principles of Functional Materials for Biomedical
Applications......................................................1
Vaskuri G S Sainaga Jyothi, Valamla Bhavana,
and Nagavendra Kommineni
Functional Biomaterials for Targeted Drug Delivery Applications......33
Hemant Singh, Muzammil Kuddushi, Ramesh Singh, Sneha Sathapathi, Aniruddha Dan, Narayan Chandra Mishra,
Dhiraj Bhatia, and Mukesh Dhanka
Metallic Nanoparticles for Imaging and Therapy.....................65
Ibraq Khurshid, Hemant Singh, Alia Khan, Muzafar Ahmed Mir, Bilkees Farooq, Asif Iqbal Shawl, Shabir Hassan, Syed Salman Ashraf, Yarjan Abdul Samad, and Showkeen Muzamil
Theranostic Applications of Functional Nanomaterials Using
Microscopic and Spectroscopic Techniques...........................87
Sahil Tahiliani, Nishtha Lukhmana, and Shyam Aravamudhan
Next-Generation Therapies for Breast Cancer........................119
Anindita De, Sonam Patel, and K. Gowthamarajan
Nanostructures-Based Polymeric Composite for Theranostic
Applications......................................................147
Poonam Jain, K. Gireesh Babu, Alle Madhusudhan, and Mitchell Lee Taylor
Functional Biomaterials for Image-Guided Therapeutics of Solid
Tumor............................................................181
Sauraj
vii

viii
Development in Biosensor-Based Diagnostics for Bacterial
Diseases: Opportunities and Challenges.............................197
Arka Sanyal, Priya Mitra, Tanima Dey, Debatri Dutta, Koustav Saha,
Arunima Pandey, and Ritesh Pattnaik
Nanostructured Electrodes as Electrochemical Biosensors
for Biomedical Applications........................................241
Rajlakshmi Chetty, Varun Pratap Singh, Alle Madhusudhan,
Raymond Wilson, and Alberto Rodriguez-Nieves
State of the Art in Integrated Biosensors for Organ-on-a-Chip
Applications......................................................263
Tanima Dey, Priya Mitra, Binita Chakraborty, Arka Sanyal,
Aditi Acharjee, Anushikha Ghosh, and Dindyal Mandal
Nanotherapeutics for Rheumatoid Arthritis Therapy.................305
Poonam Jain, K. Gireesh Babu, Alle Madhusudhan,
and Sashikantha Reddy Pulikallu
Screen-Printed Electrode (SPE)-Based Biosensor for Point-Of-Care
(POC) Diagnostic in Medical Applications, Their Scope,
and Challenges....................................................331
Dinesh Rotake, Shruti Patle, and Shiv Govind Singh
Next-Generation Therapies for Type 2 Diabetes Mellitus..............347
Debarun Patra, Soumyajit Roy, Palla Ramprasad, and Durba Pal
Quantum Dots for Theranostic Applications.........................377
Swati Sharma, Pawan Kumar Pandey, Hemant Singh, Indu Yadav,
Shiv Dutt Purohit, and Narayan Chandra Mishra

About the Editors
Alle Madhusudhan is currently working as a Postdoc-
fellow at The University of Memphis, TN, U.S.A.
Earlier he worked as a Research Professor at Department
of Biomedical Science & Institute of Bioscience and
Biotechnology, Kangwon National University, South
Korea and also worked as an Associate Professor at
Department of Chemistry, Gondar University, Gondar,
Ethiopia (2014–2018). During this period, he served as
a Coordinator of MSc (Chemistry) Programs and as
the Head of the Chemistry Department. Four students
submitted their master’s thesis under his supervision. He
received his doctorate from Department of Chemistry,
Osmania University, India (2013), where he worked on
the research projects sponsored by University Grants
Commission, India. He has more than 18 years of expe-
rience in teaching and research in both academia and
industry. He has published more than 70 scientiﬁc papers
in SCI/SCIE-grade journals (>1900 citations; h-index =
22) as a ﬁrst and corresponding author and published 1
book and 11 book chapters (Springer and Elsevier). He
is also listed as a potential reviewer for many reputed
international journals. He is also a member of Ethiopian
chemical society and Indian chemical society. He has
presented his work in several national and interna-
tional conferences in India, Ethiopia, South Korea, and
U.S.A. He has conducted two research projects spon-
sored by University Grants Commission (UGC), New
Delhi, India. His current research interests include liquid
biopsy, cancer biology, polymeric nano-drug delivery
systems, biomaterials for sustainability and catalysis.
Extraction and chemical modiﬁcation of nanocellulose
ix

x About the Editors
from lignocellulosic biomass, green synthesis of metal
and metal oxide nanoparticles on nanocellulose support
and their novel applications in biomedicine, biosensors,
and catalysis.
Shiv Dutt Purohit is currently working as Interna-
tional Research Professor (Assistant Professor) at the
School of Chemical Engineering, Yeungnam University,
Gyeongsan, South Korea. He obtained his Ph.D. from
the Department of Polymer and Process Engineering,
Indian Institute of Technology Roorkee, in 2021. He
is Materials Scientist, and his research interests lie in
biomedical and related areas such as tissue engineering
and wound healing. Besides, he is also intrigued to work
in other areas such as food packaging materials. He has
published more than 20 research articles and chapters
and has more than 500 citations on his name with an h-
index of 10. He is also Reputed Reviewer for several
peer-reviewed international journals and working as
Academic Editor for Scientiﬁca-Hindawi. He is also
involved in the editing of a few special issues in SCIE
journals.
Rajendra Prasad is currently working as Assistant
Professor at the School of Biochemical Engineering,
Indian Institute of Technology (BHU), Varanasi, India.
Prior to this position, Rajendra Prasad had postdoctoral
trainings from Tufts University, Medford, Boston, MA,
USA, NOVA Medical School, Faculdade de Ciências
Médicas Campo Mártires da Pátria, Lisboa, Portugal and
Technion-Israel Institute of Technology, Haifa, Israel,
and Indian Institute of Technology, Bombay, India, in
the area of Cancer NanoMedicine and targetable cancer
theranostics. Moreover, Rajendra Prasad had a chance
to help few master students during my postdoctoral
trainings, which gave me a conﬁdence to handle scien-
tiﬁc challenges and lead independent research projects.
Rajendra Prasad has also cracked prestigious Postdoc-
toral Fellowships such as IPDF, PBC, and JSPS and hold
my membership for Royal Society of Chemistry.

About the Editors xi
Azamal Husen is presently working as a Professor
at Sankalchand Patel University, Visnagar, India; and
Adjunct Professor at Graphic Era (Deemed to be Univer-
sity), Dehradun, Uttarakhand, India. He is also working
as a Visiting Professor at University Putra Malaysia,
Selangor, Malaysia. Previously, he served as Professor
and Head of the Department of Biology, University of
Gondar, Ethiopia; and worked as a Foreign Delegate
at Wolaita Sodo University, Wolaita, Ethiopia. He also
worked as a Visiting Faculty of the Forest Research Insti-
tute and the Doon College of Agriculture and Forest
at Dehra Dun, India. His research and teaching expe-
rience of 25 years encompasses biogenic nanomaterial
fabrication and application; plant responses to nanoma-
terials; plant adaptation to harsh environments at the
physiological, biochemical, and molecular levels; herbal
medicine; and clonal propagation for improvement of
tree species. He has conducted research sponsored by
the World Bank, the National Agricultural Technology
Project, the Indian Council of Agriculture Research,
the Indian Council of Forest Research Education, and
the Japan Bank for International Cooperation. Husen
has published extensively (over 250) and served on
the Editorial Board and as reviewer of reputed jour-
nals published by Elsevier, Frontiers Media, Taylor &
Francis, Springer Nature, RSC, Oxford University Press,
Sciendo, the Royal Society, CSIRO, PLOS, MDPI, John
Wiley & Sons, and UPM Journals. He is on the advisory
board of Cambridge Scholars Publishing, UK. He is a
fellow of the Plantae group of the American Society
of Plant Biologists, and a member of the International
Society of Root Research, Asian Council of Science
Editors, and International Natural Product Sciences. He
is Editor-in-Chief of the American Journal of Plant
Physiology, and a Series Editor of Exploring Medicinal
Plants (Taylor & Francis Group, USA); Plant Biology,
Sustainability, and Climate Change (Elsevier, USA);
and Smart Nanomaterials Technology (Springer Nature,
Singapore).

Basic Principles of Functional Materials
for Biomedical Applications
Vaskuri G S Sainaga Jyothi, Valamla Bhavana, and Nagavendra Kommineni
Abstract
applications playing critical role in drug delivery design. Currently, numerous mate−
rials of synthetic (metallic and nonmetallic systems) and natural origin are exten−
sively studied to surpass the limitations of conventional approaches. In a broader
context, functional nanomaterials are used to accomplish targeted delivery and reduce
toxic effects. They exhibit an extensive variability of physical and chemical prop−
erties, allowing for the ﬁne−tuning of biocompatibility, biodegradability, stimuli−
responsiveness, and bioactivities. These functional materials, with different patterns
and versatile functionality, are exhibiting considerable applications in diagnosis,
controlled delivery of therapeutic agents, efﬁcient adjuvants of immunotherapy,
regenerative medicine, and medical devices. This book chapter provides an insight
on the basic principles and applications of the revolutionized functional materials.
Keywords ∙Targeted delivery ∙Biomedical applications ∙
Stimuli−responsiveness
1 Introduction
Material science is indispensable in the ﬁeld of biomedical applications including targeted delivery, bioimaging, biosensing, and tissue engineering. Advancement of
nanotechnology in the ﬁeld of material science has revolutionized the ﬁeld of biomed−ical sciences which enabled the ease of targeted drug delivery and diagnosis [
1–3].
Notwithstanding, customization of nanomaterials is to be accomplished to liberate
V. G. S. S. Jyothi
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research,
Hyderabad, Telangana, India
N. Kommineni (B)
Center for Biomedical Research, Population Council, New York NY−10065, USA
e−mail: [email protected]
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2024
A. Madhusudhan et al. (eds.),
and Their Theranostics Approaches
https://doi.org/10.1007/978−981−99−6597−7_1
1

2 V. G. S. S. Jyothi et al.
the desired properties. Functionalization is the strategic method to engineer the nano−
materials that eventually leads to improved efﬁcacy eventually diminishing its side
effects, due to targeted delivery and active uptake into the cells. Functionalization
leads to the variability of the physical and chemical properties of the nanomaterials,
rendering the incorporation of desired function to the material [
4].
Functionalization is the deliberate bonding of atoms or molecules to material
customizing the physicochemical properties of the carrier system [5]. The purpose
of functionalization of the carrier material is to incorporate the required properties enabling it to be multifunctional [
6]. Some of the primary objectives of function−
alization are to reduce cytotoxicity, enhance stability, and to achieve targeting and
diagnosis (Fig. 1). However, progress of chemical methods in the arena of nano−
materials is the utmost requirement for its advancement. Numerous methods have
been explored in the chemical conjugation and functionalization of nanomaterials
speciﬁcally to achieve targeted delivery, in tissue engineering and for diagnostic
purposes [7]. The continuous efforts in the research of functional materials help in
the technological advancement in diagnosis and pharmacotherapy. Functional mate−
rials with different patterns and versatile functionality are manifested with a variety
of nanomaterials.
Fig. 1
functionalized materials

Basic Principles of Functional Materials for Biomedical Applications 3
2 Different Categories of Functional Materials Explored
Functional materials are easily processed into various device modalities, such as lipo−
somes, polymeric nanoparticles, inorganic nanoparticles for instance quantum dots
(QDs), magnetic nanoparticles, and carbon nanotubes (CNTs) (Fig.
2). So, the most
widely explored functional materials in the ﬁeld of biomedical applications including QDs, CNTs, magnetic nanoparticles, silica nanoparticles, lipid−based nanocarriers, and polymeric nanoparticles are being discussed here (Table
1).
2.1 Carbon Nanotubes
CNT is one of the allotropes of carbon, for example graphite, diamond, amorphous carbon, and fullerene [
30]. They are considered as one of the novel and promising
nanomaterials in biomedical relevance with prominent applications [31, 32]. They
are widely utilized in the delivery of drugs, biomolecules, and for achieving active targeting to the site of action. Additionally, unparalleled electrical and optical proper− ties of CNTs enable them as essential candidates in biosensing and diagnostic applica−
tions [
33]. Nevertheless, CNTs were found to be cytotoxic which limit their utilization
in biomedical ﬁeld [34]. To surmount the cytotoxicity and facilitate targeting, func−
tionalization of CNTs is being explored in the ﬁeld of biomedical applications [35].
Functionalized CNTs were reported for their use in bone regeneration [18] cancer
therapy, and diagnosis [19, 20] and also in the biosensing [23], angiographic imaging
[24], and molecular targeting [25]. Functionalization also enabled CNT biocompat−
ible and enhanced the permeability across the biological membranes. Functionalized CNTs have gained immense popularity in the ﬁeld of theranostics due to their unique
Fig. 2

4 V. G. S. S. Jyothi et al.
Table 1
Application
Functional material
Active ingredient
Description
References
Wound healing
Carbon quantum dots
Gentamicin sulfate
and diammonium
citrate
Peilili et al. synthesized antibacterial carbon quantum dots with low−drug resistance self−healing hydrogel with potent wound healing for treating bacterial infections
Li et al. [
8
]
Biosensor for cholesterol sensing
Nanocomposites of quantum dots
–
Adel et al. synthesized nitrogen graphene quantum dots and copper indium sulﬁde/zinc sulﬁde QDs for cholesterol sensing. The ﬂuorescent nanocomposite showed a highly sensitive, selective nonenzymatic cholesterol optical biosensor in 0.312–5 mM cholesterol
Adel et al. [
9
]
Imaging of microbial cells
Nitrogen−doped carbon quantum dots
–
Jain et al. synthesized nitrogen−doped grapheme quantum dots with
photoluminescence ability for bioimaging of microbial cells including E. coli and Saccharomyces cerevisiae yeast
Jain et al. [
10
]
Targeted drug delivery and bioimaging tool
Folic acid−based carbon dot
Doxorubicin
Sarkar et al. developed folic acid−based carbon dot functionalized stearic acid−g−polyethyleneimine amphiphilic nanomicelle for targeted doxorubicin delivery and imaging for triple−negative breast cancer
Sarkar et al. [
11
]
(continued)

Basic Principles of Functional Materials for Biomedical Applications 5
Table 1
Application
Functional material
Active ingredient
Description
References
Targeted delivery of
doxorubicin
Maltose−functionalized dendrimer/ graphene quantum dots
Doxorubicin
Karimi et al. prepared maltose−functionalized dendrimer/ graphene quantum dots as a pH−sensitive biocompatible carrier for targeted delivery of doxorubicin
Karimi and Namazi [
12
]
Targeted delivery of telmisartan
Chitosan Fe
3
O
4
magnetic
nanoparticles
Telmisartan
Dhavale et al. grafted chitosan on Fe
3
O
4
magnetic nanoparticles and used
as a carrier of poorly water−soluble anticancer drug telmisartan
Dhavale et al. [
13
]
Imaging and targeted delivery in breast cancer cell
FITC functionalized magnetic nanoparticles
Cinnamaldehyde
Folate mediated targeted delivery of cinnamaldehyde loaded and FITC functionalized magnetic nanoparticles in breast cancer: in vitro, in vivo and pharmacokinetic studies
Shetty et al. [
14
]
Quercetin drug delivery
Functionalized magnetite nanoparticle by chitosan
Quercetin
Quercetin−loaded magnetite nanoparticles exhibited greater toxicity against MCF−7 cells compared to quercetin−free magnetic nanoparticles
Askar et al. [
15
]
Functionalized
boron−dipyrromethene
magnetic nanoparticles
Magnetic nanoparticles
–
Scanone et al. developed functionalized
magnetic nanoparticles with
boron−dipyrromethene for bioimaging
and antimicrobial activity. They used
the modiﬁed nanoparticles to produce
ﬂuorescent images of bacterial cells
and photoinactivate pathogens
Scanone et al. [
16
]
(continued)

6 V. G. S. S. Jyothi et al.
Table 1
Application
Functional material
Active ingredient
Description
References
Bioimaging of liver
Polymeric micelles−coated magnetic
nanoparticles
–
Popescu Din et al. developed polymeric micelles−coated magnetic nanoparticles for in vivo bioimaging of liver
Popescu Din et al. [
17
]
Bone regeneration
Functionalized multiwall carbon nanotubes
–
Shrestha et al. engineered a novel ﬁbrous scaffold with the aid of zein and chitosan into polyurethane with functionalized multiwall carbon nanotubes as a bone cell repair material for bone regeneration
Shrestha et al. [
18
]
SWCNT bioconjugate
Annexin A5 functionalized single−walled CNTs
Anti−CTLA−4
Annexin A5 functionalized single−walled CNTs bioconjugate synergistically enhances an anti−cytotoxic T−lymphocyte−associated protein 4 dependent abscopal response
McKernan et al. [
19
]
Anticancer drug carriers
Functionalized single−walled carbon nanotubes
5−Fluorouracil
Ershadi et al. investigated the electronic properties of the combination metallic ((4,0)) or semiconductive ((8,0)) single−wall carbon nanotubes plus 5−Fluorouracil
Ershadi et al. [
20
]
Bioimaging and biosensing of acute myeloid leukemia
Sgc8−aptamer with luminescent terbium (III) complexes with thiacalix[4]arenesulfonate−doped silica nanoparticles
–
The Sgc8 aptamer conjugated silica nanoparticles showed afﬁnity to CCRF−CEM and Jurkat cells with ﬂow cytometry selectively. The resulted nanoparticles were promising agent for diagnosis and therapy of acute myeloid leukemia creating an opportunity for bioimaging and biosensing
Grechkin, [
21
],
Gubala [
22
]
(continued)

Basic Principles of Functional Materials for Biomedical Applications 7
Table 1
Application
Functional material
Active ingredient
Description
References
Biosensors
Functionalized multiwalled carbon
nanotubes
–
Wang et al. developed functionalized multiwalled carbon nanotubes biosensors that mimic the hierarchically helical assembly of tissues for chronic chemical monitoring in vivo
Wang et al. [
23
]
Angiographic imaging
Oxygen−doped carbon nanotubes
–
Takeuchi et al. developed oxygen−doped carbon nanotubes with phospholipid−polyethylene glycol coating to provide bioafﬁnity and showed prominent ﬂuorescence and Raman signals in spleen and liver; the signals remained for 1 month
Takeuchi et al. [
24
]
Nanosensors for molecular targeting
Biotin functionalized single−walled carbon nanotubes
–
Chio et al. developed dual functionalized single−walled carbon nanotube nanosensors for molecular
targeting and evaluated its functionality by attaching biotin as an afﬁnity pair with avidin protein
Chio et al. [
25
]
Gene delivery
Protein liposomes
–
Wang et al. prepared transferrin−modiﬁed liposomes for the targeted delivery of acetylcholinesterase therapeutic gene to liver cancer
Wang et al. [
26
]
(continued)

8 V. G. S. S. Jyothi et al.
Table 1
Application
Functional material
Active ingredient
Description
References
Targeted delivery for spinal
cord injury
Functionalized liposomes
–
Wang et al. prepared orally administered targeted delivery system in which the neuropeptide apamin, stabilized by sulfur replacement with selenium, was adopted as a targeting moiety, and the liposome surface was protected with a noncovalent cross−linked chitosan oligosaccharide lactate layer
Wang et al. [
26
]
Targeted delivery of toll−like receptor (TLR) agonists
C3 targeted liposomes
–
Francian et al receptor agonists, within the C3−liposomes, including monophosphoryl lipid A, R848, and CpG 1826, speciﬁc for TLR4, TLR9 and TLR7/8
Francian et al. [
27
]
(continued)

Basic Principles of Functional Materials for Biomedical Applications 9
Table 1
Application
Functional material
Active ingredient
Description
References
Drug delivery to colon
cancer cells
Polymeric nanoparticles
Alpha mangostin
Andrade et al. formulated genipin and Eudragit
®
L100 modiﬁed
αthiolated chitosan nanoparticles for colon−targeted drug delivery against colorectal cancer cells using pH−dependent composite mucoadhesive nanoparticles
Andrade et al. [
28
]
Targeted nanodelivery
Polymeric nanoparticle
–
Treekoon et al. synthesized iodo−substituted aza−BODIPY encapsulated nanoparticles via the nanoprecipitation method using the amphiphilic poly(ethylene glycol)−
polymer (PEG−
nanodelivery system
Treekoon et al. [
29
]

10 V. G. S. S. Jyothi et al.
properties. One of the signiﬁcant beneﬁts of functionalized carbon nanotubes is their
ability to act as multifunctional agents for both imaging and therapeutic applications.
They can be used as diagnostic agents to detect diseases or pathological conditions
and simultaneously act as therapeutic agents to treat the disease [
36]. Addition−
ally, the functionalized CNTs have high surface area, excellent biocompatibility, and tunable optical and magnetic properties, which make them suitable for targeted drug delivery and imaging [
37]. Overall, functionalized carbon nanotubes hold great
potential for theranostic applications and can play a crucial role in the development of personalized medicine in the future.
2.2 Silica Nanoparticles
Silica nanoparticles are extensively investigated in biomedical applications owing to their low toxicity, exceptional biocompatibility, and high surface area [
38–40]. It is
feasible to control the size, crystallinity, shape, and porosity of the silica nanopar− ticles. Besides, surface chemistry of the silica nanoparticles can be fabricated to
amend loading of drug, circulation half−life, and enable targeted delivery [
41]. Silica
nanoparticles doped with dye can be used as a potential ﬂuorescent nanoprobe with ﬂuorescent capabilities similar to heavy metal. The ability to amalgamate these prop−
erties renders silica nanoparticles an enviable arena for biosensing, drug delivery, monitoring, and ablative therapies [
42]. Sgc8 aptamer conjugated silica nanoparti−
cles were used in bioimaging and biosensing of acute myeloid leukemia [22]. Folic
acid−conjugated polyglycerol−grafted Fe
3O4@SiO2 nanoparticles were prepared for
targeting ovarian cancer. The results showed the preferential uptake of nanoparticles by the carcinoma cells (SKOV−3) derived from human ovary. A study on the func−
tionalization of silica nanoparticles with a glypican−3 (GPC3) targeting peptide for ultrasound molecular imaging of human hepatocarcinoma cells was performed. A simple co−precipitation method was used to synthesize the nanoparticles and then
conjugate them with the targeting peptide. The results of the study showed that the GPC3−targeting nanoparticles had a high binding afﬁnity to hepatocarcinoma cells and could effectively enhance the ultrasound imaging signal. The study also found
that the nanoparticles had a low cytotoxicity and were biocompatible [
43].
2.3 Quantum Dots
QDs are nanoscale particles which are semiconductor crystals with distinctive elec− tronic and optical properties such as bright and intensive ﬂuorescence [
44]. QDs
discriminate the conventional organic label dyes by high absorption of light yielding high quantum and large extinction coefﬁcient. They offer extensive observation period with good sensitivity during observation under ﬂuorescence microscope. They
are most widely implemented in theranostic purposes enabling diagnosis and therapy

Basic Principles of Functional Materials for Biomedical Applications 11
simultaneously in the multidisciplinary ﬁelds like physics, chemistry, nanotech−
nology, material sciences, drug delivery, and pharmacology [45]. However, the
uncoated QDs tend to undergo photochemical degradation, surface oxidation, aggre−
gation, and even leaching of metal ions on long−time exposure in the biological ﬂuids
[46]. This makes them unsuitable for biomedical applications. Functionalization of
quantum dots is the emerging ﬁeld in the biological applications which makes them
conquer all the limitations associated with it. They are used in wound healing [8],
imaging of microbial cells, [10] targeted delivery of doxorubicin in cancer therapy
[11, 12], and also used as nanozymes [47].
2.4 Magnetic Nanoparticles
Magnetic nanoparticles are the promising materials in the biomedical application with the areas focusing on diagnosis, targeted therapy, hyperthermia, and tissue
engineering [
48]. Nonetheless, functionalization of magnetic nanoparticles is essen−
tial to execute the multifunctions in the biomedical ﬁeld [49]. It empowers the
magnetic nanoparticles biocompatible, increases water solubility, and is bio−speciﬁc, making them potential carriers in the pharmacotherapy and diagnosis. Functionalized magnetic nanoparticles were used in targeted delivery of telmisartan, cinnamalde−
hyde [
13, 14]. Functionalized magnetic nanoparticles have been used for various
applications including targeted drug delivery, magnetic hyperthermia, and magnetic resonance imaging (MRI). They have been shown to improve the efﬁcacy of
chemotherapy drugs and reduce the toxicity associated with these treatments. They can also be used to destroy cancer cells through magnetic hyperthermia, where the nanoparticles generate heat when exposed to a magnetic ﬁeld [
50]. In addition, it can
be used as contrast agents in MRI, providing high−resolution images of tissues and organs.
2.5 Lipid-Based Carriers and Colloidal Systems
Liposomes, lipid, and polymeric nanoparticles have evolved as prominent carriers in the pharmaceutical formulation development. They have been vastly explored
in the biomedical applications. They have demonstrated as highly effective drug carriers as compared to the conventional drug delivery system. However, fabrica−
tion of liposomes, lipids and polymeric nanoparticles with longer blood circulation and site−speciﬁc drug delivery is still an ongoing research objective which needs to be achieved [
51]. One exciting means to accomplish targeting delivery is ligand
tagging, such as peptides or monoclonal antibodies, to the carrier [52]. So, liposomes,
lipid, and polymeric nanoparticles are extensively studied for the functionalization to achieve the targeted delivery and to escape from the reticular endothelial system.

12 V. G. S. S. Jyothi et al.
Functionalized liposomes were reported to target the spinal cord injury [53]. Poly−
meric nanoparticles were prepared for colon targeting where the polymer exhibited
pH−dependent release of Alpha−mangostin [28] and celecoxib [54].
2.6 Basic Principles of Functionalization
Functionalization is the key to incorporate the desired properties to the materials which can be characterized as an intentional addition of functional groups on the
surface of nanoparticles to accomplish surface moderation that renders them viable by improving the desired physical, chemical, and mechanical properties. Function− alization can be achieved by binding the functionally active moiety on the surface
of nanoparticles and conjugating or interacting the nanoparticle with the carrier or ligand molecule [
55].
One of the beneﬁcial outcomes of functionalizing is that the required character−
istics in the nanomaterial can be superintended in a predictable approach to ﬁt the speciﬁc applications. The procedure utilized to produce, customize, and organize
functionalized materials presents exaggeratedly new opportunities for the advance of new multifunctional tools for biological and pharmaceutical relevance.
Functionalization of materials involves the molecular level of interaction with the
functional moiety. Subsequently, numerous categories of materials are used for the biomedical applications. Thus, different materials involve different approaches to functionalize. Covalent and noncovalent interactions like electrostatic interactions,
hydrogen bonding, and Van der Waals forces are widely involved in these reactions.
2.7 Carbon Nanotubes
CNTs, when generated originally, are not soluble in water and biological ﬂuids and, therefore, elevate their need to enhance solubility and dispersion in the biorel− evant ﬂuids. Apart from solubility and dispersibility, reducing its cytotoxicity and
improving biocompatibility and enabling them site speciﬁc and bioimaging is also essential. Hence, surface modiﬁcation of CNTs is gaining importance in the biomed− ical ﬁeld. CNT surface chemistry, as well as the methods used to purify and function−
alize them, has a signiﬁcant impact on both their biological activities and cytotoxic effects. It also aids in targeted delivery, biosensing, and bioimaging by tagging the
CNTs with appropriate ligands.
Among all the methods followed for functionalization (Fig. 3), noncovalent and
covalent surface modiﬁcations are two frequently used methods. Recently, a study
explored the use of CNT for bone regeneration where the CNTs were functionalized
with chitosan and zein by covalent bonding [18].

Basic Principles of Functional Materials for Biomedical Applications 13
Fig. 3
2.7.1 Noncovalent Functionalization
In order to improve solubility of CNTs making them less toxic, biocompatibility,
protein assembly, and drug delivery, noncovalent functionalization is regarded as one
of the vital means as no considerable alteration in structure and physical properties
occurs [56]. CNTs interact noncovalently with various molecules via weak interac−
tions such as surface adsorption onto the side walls of CNTs,
π
bonding, and van der Waals force [57, 58]. Many polymers, biomolecules, and surfac−
tants have been explored for the noncovalent functionalization of CNTs to make them
biocompatible. Sodium dodecyl sulfate (SDS) was the most widely used surfactant
to yield individual single−walled CNTs (SWCNTs) under ultra−sonication and ultra−
centrifugation conditions [
59]. Instead of surfactants, polymers have been tried to
enhance dispersion. However, the observations revealed that polymers are inefﬁcient as compared to surfactants. Correspondingly, surfactants with different charges and nonionic charges are also strived for their effectiveness in enhancing dispersion of
SWCNTs, however, the quantity of surfactants used is lower than 5% [
60].

14 V. G. S. S. Jyothi et al.
2.7.2 Covalent Functionalization
Direct covalent functionalization can notably modify the solubility, provide better
stability, accessibility, and reduce leaching and render compatibility of CNTs [61].
Thus, covalent functionalization is one of the widely utilized methods for surface modiﬁcation of CNTs. Diimide−activated amidation is the most frequently used means to couple the CNTs with proteins. Coupling agents are being employed
in coupling of proteins and peptides to the CNTs where
aminopropyl) carbodiimide hydrochloride (EDAC) or N, N’−dicyclohexyl carbodi− imide (DCC) is being widely used [
62]. Biomolecules can be grafted covalently on
the surface of CNTs. For example, multiwalled CNTs were covalently bonded with the polyetherketones in phosphoric acid media [
63]. Also, the covalent modiﬁcation
of the nanotube sidewalls totally changes the electronic properties of the CNTs. The
reliability of covalent functionalization implementation in CNTs is based on the type
of biomolecule used and the desired function to be attained.
2.7.3 Functionalizing by Oxidation
Oxidation of CNTs is the stand−alone technique for the functionalization. It marks in addition of oxygen to the surface of the CNTs’ side walls making them soluble
in water and biological ﬂuids. Oxidation leads to the introduction of carboxyl or hydroxyl groups on CNTs [
64]. Sulfuric acid or nitric acid was used to oxidize CNTs.
Acid treatment opens the tubes and creates holes on the surface to which carboxyl,
sulfate, and hydroxyl groups are attached [65]. Functionalization makes the CNTs
hydrophilic and soluble in aqueous solvents and diminishing its cytotoxicity. Various
functional groups can be introduced onto the surface of CNTs. Oxidized CNTs can
be functionalized further by esteriﬁcation, amidation, etc. [66]. Various proteins were
found to be absorbed spontaneously and nonspeciﬁcally onto the sidewalls of CNTs.
They act as carriers and deliver the proteins and other biomolecules directly into the
mammalian cells.
2.8 Silica Nanoparticles
Silica nanoparticles are usually functionalized to enhance the colloidal stability and
solubility in the biological ﬂuids, improve biocompatibility, enhance high cellular
uptake, enable bioimaging, and promote site−speciﬁc delivery [67]. Thereby, surface
modiﬁcation of silica nanoparticles plays an important role in inﬂuencing the inter−
action of functionalized silica nanoparticles with the physiological environment,
biodistribution, cellular internalization, and disease targeting [68]. Currently, there
are three main chemical methods to functionalize nanosilica which are post−synthetic
grafting, co−condensation, and polymer coating (Fig. 3).

Basic Principles of Functional Materials for Biomedical Applications 15
2.8.1 Post-synthetic Grafting
Silica nanoparticles are usually functionalized by post−synthesis grafting for surface
modiﬁcation. Different organic and inorganic silane precursors, for instance,
alkoxysilanes/halosilanes, are incorporated into the silica nanoparticles and are being
used for cellular imaging, drug targeting, etc. [69]. Silanes and silanols are coupled
to the surface of silica by hydrolysis. Nevertheless, the post−synthesis grafting often
leads to heterogeneous chemistry, where pore opening shows higher density of
grafting and interior framework shows lower efﬁciency.
Alkoxysilanes and halosilanes undergo condensation reaction with the silanol
groups on the surface of silica forming 1−3 Si−O−Si links where the halosilanes clas− sically hydrolyze substituting the halide for alcohol group forming 1−3 Si−O−Si links [
70]. However, halosilanes react directly with silanol groups on the surface in the
anhydrous condition. Most often, 3−mercaptopropyl trimethoxysilane (MPTS) and 3−aminopropyl triethoxysilane (ATPS) are being used for functionalization of silica nanoparticles [
71]. Subsequently, PEGylation is the most frequently used function−
alization method to improve the pharmacokinetics of drug molecules by alteration of circulation half−life and enhances the solubility, stability, and biocompatibility
of nanoparticles. Bovine serum albumin (BSA) is also used more usually in low concentration to improve the stability of nanoparticles [
72].
Silica is also conjugated with the antibodies via a linker group through the func−
tional moiety on the surface of silica and amino acid residues. Linker group prevents the interaction between the antibody and silica protecting it from denaturation by creating a space between the silica and antibody. The linker groups are available as
monovalent or multivalent based on the functional groups available on the surface of the linker. For instance, monovalent linker with glutaraldehyde functional group makes imine covalent bond between the amino residue on the biomolecule and the
amine group on the surface of nanosilica [
69]. However, these linkers are coupled
with few limitations like aggregation and thereby stability in the biological ﬂuid.
2.8.2 Co-condensation
In co−condensation method, functionalization of silica nanoparticles is carried out during the synthesis process. It is a one−pot synthesis process where the functional organic groups are incorporated directly into the silica framework via sol–gel method
[
73]. Organosilanes are the functional organic groups widely used for the functional−
ization of nanoparticles where they are added to the reaction mixture containing the
tetrafunctional silane. This technique aids in the functionalization of internal surface
of mesoporous silica nanoparticles [74].
However, the degree of functionalization depends on the nature of co−condensing
agents and its concentration and size. Alkoxysilanes or halosilanes are used as condensing agents same as with the post−synthetic grafting. These alkoxy or haloxysi− lanes form 1−3 Si−O−Si links with the surface silanol groups [
75]. However, halosi−
lanes substitute the halide with alcohol by hydrolysis forming 1−3 Si−O−Si link.

16 V. G. S. S. Jyothi et al.
APTS and MPTS are the most frequently used functional moieties for functional−
ization of silica. Co−condensing agents also impact the shape of the particles where
hydrophobic agents yield rod−shaped particles while hydrophilic agents yield round
particles.
2.9 Polymer Coating
Coating of silica nanoparticles with the polymer can be attained by physical absorp−
tion and chemical conjugation. Silica has negative charge on its surface which
has the afﬁnity toward the positively charged polymers [76]. The modiﬁed silica
surface can accommodate various biomolecules which include polypeptides, carbo−
hydrates, nucleic acids, and antibodies [77]. The versatile chemical nature of silica
surface makes the conjugation of functional moieties reliably easy. Thus, the desired
characteristics can be incorporated in the silica nanoparticles by functionalization
approach.
2.10 Quantum Dots
QDs are the potential nanoprobes being explored in the biomedical applications
such as drug delivery, biomolecules delivery, site−speciﬁc delivery, and theranostic
approaches [78]. However, functionalization is the crucial step in utilizing the QDs
for multifunctional purposes as QDs are suffering from stability issues, insolubility
in aqueous solutions [79]. Even for achieving the targeted delivery, conjugation of
ligands onto the surface of QDs is essential which is in turn achieved by functionaliza− tion [
80]. Originally, synthesized QDs are hydrophobic in nature where hydrophiliza−
tion of QDs is the ﬁrst step in utilizing the QDs for biomedical applications. Conse−
quently, bioconjugation of QDs after their hydrophilization results in a multifunc−
tional nanoparticle that conglomerates the electrochemical/optical properties of QDs
with the biological utility of the biomolecule.
2.10.1 Hydrophylization
Mainly three approaches are used to hydrophilize the QDs which include ligand
exchange, silanization, and encapsulation (Fig. 4).
(i) Ligand exchange
In this method, the ligands with bifunctional molecules are exchanged with the
original hydrophobic coating. These bifunctional ligands are water soluble with one
end is being attached to the surface of QD and the other end is free to conjugate with

Basic Principles of Functional Materials for Biomedical Applications 17
Fig. 4
a biomolecule [81, 82]. The most commonly used ligands used in this technique are
trioctylphosphine oxide (TOPO), trioctylphosphine (TOP), tetradecyl phosphonic
acid (TDPA), oleic acid, and hexadecyl amine (HDA) [83, 84]. These ligands prevent
aggregation of nanoparticles and their growth and passivate its surface defects to
preserve quantum yield [85]. Organic ligands offer exceptional stability and solu−
bility to the QDs where the exchange process occurs in the organic noncoordinating
solvents via simple mass action [86].
Ligands pre−existing on the surface of QD are in dynamic equilibrium with the
surrounding solvent. Hence, the ligands are in continuous motion where the ligand
on the surface leaves the QDs, whereas free ligands in the solution occupy and
attach the available sites on the surface of QD. Thereby, the new hydrophilic ligands
intended to attach to the QD are added to the solvent where the pre−existing ligands
which are in dynamic equilibrium are exchanged with the new added ligands [
87].
However, to achieve this ligand exchange process successfully, the concentration of the newly added ligand should be equal to the concentration of the pre−existing
ligand and should have high afﬁnity toward the QDs. Conversely, the newly added/ replacing ligand with low afﬁnity to the surface of QD can also be used in this technique by increasing the concentration of ligand thus enhancing the probability
of attachment of replacing ligand [
88]. The most widely used ligands for the ligand
exchange technique are polymers with functional groups such as carboxyl and amine and thiol, which can replace the existing ligands on the surface of the QDs.
(ii) Silanization
Silanization is the process of coating the QDs with a layer of amorphous silica
[89]. This technique is similar to the ligand exchange process. However, it is regarded
as a separate technique due to its prevalent use in the hydrophilization of QDs. In the
ﬁrst step, the surface of the QD is activated for attaching the silane molecules to the

18 V. G. S. S. Jyothi et al.
QD. This step requires the exchange of TOPO and HDA on the surface of QD with
the polar ligands that can be easily dispersed in water or ethanol [90]. This method
is considered as highly advantageous as compared with the nanoparticles coated
with organic compounds. This method results in a shell of silica on the surface of
QDs where it achieves hydrophilization of QD. Apart from that, silica is considered
as inert, nontoxic, and optically transparent. It also provides colloidal stability to
the QDs and protects from leaching and protects physical and chemical processes.
Additionally, silica is biocompatible, and its surface can be functionalized easily
making it suitable for further conjugation with biomolecules.
(iii) Encapsulation
In this approach, the hydrophobic surface of QD is coated with a variety of carriers
which includes liposomes, polymers with amphiphilic nature [91]. The QD with
hydrophobic shell interacts directly with the coating material by physical interaction, which includes electronic or hydrophobic interactions. Large number of materials
like amphiphilic copolymers and biopolymers were used for the encapsulation of QDs [
92]. Surfactants can also be used to encapsulate the QDs, however, their weak
interactions make them unsuitable for encapsulation. Thereby, amphiphilic polymers
(PEG are widely used for encapsulation where they form very strong interaction with
the surface of QD owing to its numerous hydrophilic and hydrophobic units [93].
Liposomes are also being explored in encapsulation of QDs. Liposomes are spher−
ical vesicles with hollow structure enabling them for loading of hydrophobic QDs. The hollow structure of liposomes captivates high loading ability and loading of QDs into its hollow structure makes the QDs water soluble [
91]. It also facilitates conjuga−
tion with a variety of biomolecules including proteins, enzymes, etc. and enhances its stability and ampliﬁes its analytical signal. However, the use of liposomes as encap−
sulating agents is limited by their instability in physiological conditions and during storage. It also suffers from its sensitivity toward the slight variations in pH, temper− ature, and osmotic pressure [
94]. Nevertheless, these drawbacks can be surmounted
by templating or covering with different materials such as silica, polymers. But this method results in an increase in the hydrodynamic diameter of the particle which makes it unsuitable for biosensing and active targeting [
95].
2.10.2 Functionalization with Biomolecules
Immobilization of biomolecules on to the surface of QD involves two approaches which include covalent linking and noncovalent binding where the biomolecules
are coupled directly to the surface of QD (Fig.
4). Covalent linkage is attained by
different bioconjugation chemistry using activated functional groups at the surface of QDs, whereas noncovalent binding is established by electrostatic, hydrophobic,
or afﬁnity interactions between biomolecules and the surface of the QD.
The common tactics for the attachment of biomolecules can be classiﬁed as
covalent attachment and nonspeciﬁc adsorption.
(i) Adsorption of functional molecules

Basic Principles of Functional Materials for Biomedical Applications 19
Adsorption is the simple attachment of chemical moieties on the surface of
nanoparticles with any chemical reaction or bonds. This is the simple and highly
utilized technique for the conjugation of ligands or molecules on the surface of
nanoparticles [
77, 96]. In adsorption, electrostatic interaction, hydrogen bonding,
and hydrophobic interactions are mainly involved in this functionalization process. The large surface area on the nanoparticles can be used for the adsorption of large molecules for instance proteins, polymers, nucleic acids, and enzymes. There is no
role of functional groups in this strategy and considered as a nonselective binding technique. The electrostatic interaction observed in this adsorption strategy is seen in molecules with charges opposite to the surface of QD. For example, proteins
engineered with positively charged terminal are interacted electrostatically with the negatively charged QD resulted from the ligation of QD with carboxyl groups [
97].
Hydrogen bonding is another weak chemical interaction in adsorption where the
ligand on the surface of QD forms hydrogen bond with the biomolecules. Thereby, this adsorption technique depends on the type of molecule being involved in the conjugation process. For instance, oligonucleotides adsorb on the surface of QD
depending on the pH and type of medium, ionic strength. It was reported that pH plays a key role in adsorption of oligonucleotides where it adsorbs strongly in the acidic
pH when the carboxyl groups on the surface of QD are protonated. In the presence of alkaline or neutral pH conditions, the adsorption of oligonucleotide is considerably reduced. This suggested that the hydrogen bond is the primary mechanism involved in
the adsorption of oligonucleotide on to the surface QD [
98]. For further conﬁrmation
of the formation of hydrogen bond in the adsorption of oligonucleotide to the QD, formamide was added to the solution of QD. Formamide is a well−known molecule
which disrupts the hydrogen bonding interaction of nucleic acid. It was noticed that with the increase in concentration of formamide, there is decrease in adsorption of oligonucleotide to the QD [
99, 100]. Thus, it was evidenced that the hydrogen bond
is the main driving force for the adsorption of oligonucleotides.
Despite its easiness in the adoption of adsorption strategy, it suffers from various
drawbacks. These include lack of speciﬁcity in the adsorption of biomolecules
leading to lack of control on the number of molecules conjugating, lack of control
on the orientation of biomolecules attached to the QD and the presence of weaker
interactions between the molecules and the QD leading to competitive binding from
the host ligands with the surface of QD. Thus, assurance of the biomolecules attach−
ment onto the surface of QD and their orientation is critical in this strategy and to be
monitored carefully.
(ii) Covalent coupling of biomolecules
QDs can be coupled with the biomolecules by covalent bonding that involves
different bonds.
Amide coupling
QDs are hydrophilized with attachment of various ligands which makes them solu− bilized in the aqueous solutions. The ligand attached in hydrophilization of QD is
made in such a way that the terminal groups of ligands are –OH, –COOH, –SH

20 V. G. S. S. Jyothi et al.
or –NH2. These functional groups aids in easy conjugating with the biomolecules
such as peptides, proteins or antibodies [101]. The carboxyl−terminated functional
group on the surface of QD forms the amide bond with the amine residues in the
biomolecules. The amide bonds are formed easily in the alkaline buffered conditions
which is a simple water−soluble process [77]. This simple reaction also retains the
intact structure of the compounds and does not require any lengthy spacers. Thus,
the QDs conjugated with the amide functionality preserve the structure and also
maintain the hydrodynamic size of the particles as the size of the particle is directly
proportional to the size of the functional moiety attached on the surface of QD [102].
Thiol binding
Functionalization of QDs involves two processes, where hydrophilization of QD is followed by conjugation with the ligand. However, this thiol binding technique does
not require any solubilization method, and both functionalization and solubilization are achieved by this single step [
45]. Thus, this is an alternative to the two−step
process for the functionalization of QDs. Peptides can be customized in a way to
act as both targeting and anchoring agent [103]. The same procedure can be used
in QDs where the thiol−terminated functional group on the surface of QD can be attached to the sulfur−containing amino acid [
104]. The thiol or amine group on the
surface of QD forms thiol bond with the thiol or amine group on the proteins or DNA
or peptide. Even the stability of thiol bonds is stronger when compared to disulﬁde
bonds as the disulﬁde bonds can undergo exchange reaction in the cellular media
with the competing thiol groups. Thus, the thiol−bonded QDs can be used for the
targeted delivery of drugs, proteins, or antibodies where the release of conjugated
molecule from the QD results from the cleavage of thiol bonds by selective enzymes
present at a speciﬁc site in the body [
105].
Click chemistry
Click chemistry is the most prevailing chemical synthesis technique used in the small molecule bioconjugation reaction. It is used to couple the ligands onto the surface of
QDs. This reaction is also used to attach huge number of biomolecules and coupling agents to the QDs. The reaction was carried out at room temperature and formed a thermodynamically stable bond between the carbon and a heteroatom resulting in
a higher yield. However, the click reaction with the biomolecules results in lower yield which is resulted by the synthesis of terminal azide or alkyne groups [
106, 107].
The stability of these groups gives a stable ﬁnal reactant which can be introduced to
diverse linking groups and biomolecules. Moreover, multiple functionalities can be
achieved with the same QDs possessing the azide or alkyne termination [108, 109].

Basic Principles of Functional Materials for Biomedical Applications 21
2.11 Magnetic Nanoparticles
Chemical modiﬁcation of magnetic nanoparticles is essential to realize its biomedical
application which is achieved mainly by three different mechanisms which include
ligand addition, ligand exchange, and encapsulation (Fig.
4).
2.11.1 Ligand Addition
This method is associated with the coupling of a ligand to the surface of magnetic nanoparticles. There is no involvement in the removal of pre−existing ligands on the
surface of magnetic nanoparticles. Ligand addition is accomplished by four different ways. The ﬁrst way of addition is to conjugate the ligand to the nanoparticles with no
capping agent. The second way of addition is associated with indirect method where a layer of inorganic material is developed on the surface of magnetic nanoparticle and the ligand is adsorbed to the nanoparticle via ionic or nonspeciﬁc interactions with the
added layer [
110–112]. As the surface of magnetic nanoparticles is hydrophobic in
nature, hydrophobic moieties are capped to the surface by the hydrophobic interaction which is the third way of ligand addition. Covalent bond formation between the newly
added ligand and the pre−existing ligand also assists in the ligand addition.
2.11.2 Ligand Exchange
Ligand exchange is the exchange of pre−existing ligands with the newly added
ligands. Here, the hydrophobic ligands on the surface of magnetic nanoparticles
are replaced with the hydrophilic ligands. The detachment and attachment of ligands
depend on their strength where the hydrophilic ligand needs to be stronger than the
hydrophobic ligand in order to replace them [
113–115]. This enables the magnetic
nanoparticles soluble in the aqueous solution.
2.11.3 Encapsulation
Encapsulation is a process in which the magnetic nanoparticles capped with the hydrophobic ligands are coated with the amphiphilic materials. This coating of
amphiphilic material on the surface of magnetic nanoparticles renders them soluble in aqueous solution and makes them biocompatible. The amphiphilic material inter− acts with the ligand on the surface of nanoparticles with the hydrophobic part and the
hydrophilic part is exposed toward the solution thus forming a coat on the nanoparticle surface [
116]. Furthermore, the functional groups on the encapsulated nanoparticles
can be used for the bioconjugation of different biomolecules.

22 V. G. S. S. Jyothi et al.
Table 2
Nanocarrier
Class of chemical interaction
Bonds or interactions involved
Liposomes Covalent coupling
Thioether bond Disulﬁde bond Amide bond Hydrazide bond Amine–amine bond
Noncovalent coupling
Weak interactions
Polymeric nanocarrier Adsorption
Hydrogen bond Hydrophobic interactions
Covalent binding
PEGylation Biotinylation
2.12 Lipid-Based Carriers and Colloidal Systems
Liposomes, lipid nanoparticles, and polymeric nanoparticles are widely explored in
pharmaceutical technology and diagnosis. However, functionalization is the key to
realize all the desired functions. Binding of ligand to the liposomes and the polymeric
nanoparticles are discussed separately here (Table 2).
2.12.1 Lipid-Based Carriers
Ligands are attached to the surface of liposomes by two methods which enable them to execute multifunctional. The two coupling methods are covalent and noncovalent
binding.
(i) Covalent binding
Ligands are attached to the liposomal surface via an anchor which aids in
connecting the ligand and the liposome. The anchor with the functional groups forms covalent bonds with the ligands. The most widely used anchors are phospholipids
such as phosphatidylinositol and phosphatidylethanolamine and fatty acids such as palmitic acid [
117, 118]. Among these, phosphatidylethanolamine is the most widely
used anchor. These anchors are easily incorporated into the liposomes. However, there
are two approaches to conjugate the ligand to the liposomes via an anchor. In the
ﬁrst approach, the ligand is covalently bound to the anchor, and the resulted ligand is
mixed with the constituents of the liposome during its synthesis [
119]. In the second
approach, the anchor is mixed with the constituents of liposomes during its fabrica− tion, and thus, the anchor is incorporated in the liposome. The ligand is attached to
the preformed liposome with the aid of anchor [
120]. Thereby, functionalization of
liposomes with the ligands is achieved by the anchor molecules. The most commonly

Basic Principles of Functional Materials for Biomedical Applications 23
employed bonds in tagging the ligands to the liposome are thioether bonds, disulﬁde
bonds, amide bond, hydrazide bond, and amine–amine bond [121–123].
(ii) Noncovalent binding
Noncovalent binding is the alternative way to tag the ligand to the liposomes. It
is the easiest way of coupling ligand to the liposomes where there is no need of any
anchor molecule. The ligand is mixed with the constituents of the liposomes and
the anchor is ligated to the liposome during its formation [124]. However, practical
concerns associated with this technique are attachment of ligand to the liposome is
low about 4–40%, and the control of ligand attachment is not possible where the
orientation of biomolecules cannot be assured. It also results in physical instability
of liposomes. However, detachment of ligand from the liposomes can be assured in
the body as the bond involved is noncovalent in nature. Attempts have been made
to attach antibodies to liposomes by noncovalent interactions via heptanes [
125].
Nevertheless, the noncovalent technique for ligand attachment is still in infancy stage due to its weak interaction and random distribution of ligand on the surface of
liposome and needs to be explored much.
2.12.2 Polymeric Nanoparticles
Polymeric nanoparticles are ligated with ligands to execute various functions, and it is achieved by two different methods (Table
2).
(i) Adsorption
Fabrication of liposomes with the ligands is achieved by the adsorption which
is widely used approach to mount antibodies onto the surface of nanoparticles. The
physical adsorption of ligand on the nanoparticle surface is attained by the hydrogen
bond or by hydrophobic interaction or electrostatic interaction [126]. These interac−
tions immobilize the ligands onto the surface of nanoparticles. To avoid the chemical
reaction between the ligand and the nanoparticle, coating can be implemented which
ensures the stability of the ligated polymeric nanoparticles.
(ii) Covalent binding
Covalent coupling of ligand to the polymeric nanoparticles is also one of the
approaches to tag the ligand onto the polymeric nanoparticles. However, only very
few studies have been reported with the covalent coupling. A study was reported on
the poly(cyanoacrylate) nanoparticles where the nanoparticles are coated with PEG
and the PEG is conjugated with the transferrin as a ligand [127]. This transferrin
ligand was used to deliver the DNA to the targeted cells. In another study, poly(lactic
acid) nanoparticles were conjugated with the biotin where the biotin and poly (methyl
methacrylate−co−methacrylic acid) conjugate was precipitated with the poly(lactic
acid) to synthesize stable polymeric nanoparticles for active targeting [128]. Thus,
targeted delivery of nanoparticles can be attained by conjugating with the appropriate
ligands.

24 V. G. S. S. Jyothi et al.
3 Conclusion
Functional materials are widely explored in the arena of biomedical relevance.
Various classes of materials are being used which include quantum dots, silica
nanoparticles, carbon nanotubes, magnetic nanoparticles, etc. However, direct usage
of these materials in biomedical applications is limited due to various reasons.
Thereby, functionalization of these materials can be performed to surmount the issues
associated with them. Consequently, functionalization is considered as a prerequisite
for the versatile usage of nanomaterials in the diagnostic and therapeutic applica−
tions. Functionalization involves either the chemical reaction or a simple adsorption
of nanomaterial and a functional moiety. It aids in the attachment of biomolecules or
ligands or ﬂuorescent dyes onto the surface of the material executing multifunctions
in the biological applications.
References
1. Fenton OS, Olafson KN, Pillai PS, Mitchell MJ, Langer R (2018) Advances in biomaterials
for drug delivery. Adv Mater 30(29):1705328. https://doi.org/10.1002/adma.201705328
2. Husen A, Siddiqi KS (2023) Advances in smart nanomaterials and their applications
vier Inc., 50 Hampshire St., 5th Floor, Cambridge, MA 02139, USA https://doi.org/10.1016/
C2021−0−02202−1
3. Jin−Chul K, Madhusudhan A, Husen A (2021) Smart Nanomaterials in Biomedical Applica− tions. Springer Nature Switzerland AG, Gewerbestrasse 11, 6330 Cham, Switzerland.
https://
doi.org/10.1007/978−3−030−84262−8
4. Bao G, Mitragotri S, Tong S (2013) Multifunctional nanoparticles for drug delivery and molecular imaging. Annu Rev Biomed Eng 15:253–282.
https://doi.org/10.1146/annurev−bio
eng−071812−152409
5. Sapsford KE,Algar WR,Berti L, Gemmill KB,Casey BJ,OhE,Stewart MH,Medintz IL (2013) Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology. Chem Rev 113(3):1904–2074.
https://doi.org/10.1021/cr300143v
6. Alle M, Sharma G, Lee S−H, Kim J−C (2022) Next−generation engineered nanogold for multi− modal cancer therapy and imaging: a clinical perspectives. J Nanobiotechnol 20(1):1–34.
https://doi.org/10.1186/s12951−022−01402−z
7. Navya P, Daima HK (2016) Rational engineering of physicochemical properties of nanoma− terials for biomedical applications with nanotoxicological perspectives. Nano Convergence 3(1):1.
https://doi.org/10.1186/s40580−016−0064−z
8. Li P, Liu S, Yang X, Du S, Tang W, Cao W, Zhou J, Gong X, Xing X (2021) Low−drug resis− tance carbon quantum dots decorated injectable self−healing hydrogel with potent antibioﬁlm property and cutaneous wound healing. Chem Eng J 403:126387.
https://doi.org/10.1016/j.
cej.2020.126387
9. Adel R, Ebrahim S, Shokry A, Soliman M, Khalil M (2021) Nanocomposite of CuInS/ZnS and nitrogen−doped graphene quantum dots for cholesterol sensing. ACS Omega 6(3):2167–2176.
https://doi.org/10.1021/acsomega.0c05416
10. Jain R, Vithalani R, Patel D, Lad U, Modi CK, Suthar D, Solanki JD, Surati KR (2021) Highly ﬂuorescent nitrogen−doped graphene quantum dots (N−GQDs) as an efﬁcient nanoprobe for imaging of microbial cells. Fuller Nanotub Carbon Nanostructures 29(8):588–595.
https://
doi.org/10.1080/1536383X.2021.1872548

Basic Principles of Functional Materials for Biomedical Applications 25
11. Sarkar P, Ghosh S, Sarkar K (2021) Folic acid based carbon dot functionalized stearic acid−
g−polyethyleneimine amphiphilic nanomicelle: Targeted drug delivery and imaging for triple
negative breast cancer. Colloids Surf B: Biointerfaces 197:111382.
https://doi.org/10.1016/j.
colsurfb.2020.111382
12. Karimi S, Namazi H (2020) Simple preparation of maltose−functionalized dendrimer/ graphene quantum dots as a pH−sensitive biocompatible carrier for targeted delivery of doxorubicin. Int J Biol Macromol 156:648–659.
https://doi.org/10.1016/j.ijbiomac.2020.
04.037
13. Dhavale RP, Dhavale RP, Sahoo SC, Kollu P, Jadhav SU, Patil PS, Dongale TD, Chougale AD, Patil PB (2021) Chitosan coated magnetic nanoparticles as carriers of anticancer drug Telmisartan: pH−responsive controlled drug release and cytotoxicity studies. J Phys Chem Solids 148:109749.
https://doi.org/10.1016/j.jpcs.2020.109749
14. Shetty V, Jakhade A, Shinde K, Chikate R, Kaul−Ghanekar R (2021) Folate mediated targeted delivery of cinnamaldehyde loaded and FITC functionalized magnetic nanoparticles in breast cancer: in vitro, in vivo and pharmacokinetic studies. New J Chem 45(3):1500–15.
https://
doi.org/10.1039/D0NJ04319B
15. Askar MA, El−Nashar HA, Al−Azzawi MA, Rahman SSA, Elshawi OE (2022) Synergistic effect of quercetin magnetite nanoparticles and targeted radiotherapy in treatment of breast cancer. Breast Cancer (Auckl) 16:11782234221086728.
https://doi.org/10.1177/117822342
21086728
16. Scanone AC, Santamarina SC, Heredia DA, Durantini EN, Durantini A, s. M. (2020) Func− tionalized magnetic nanoparticles with BODIPYs for bioimaging and antimicrobial therapy applications. ACS Appl Bio Mater 3(2):1061–1070.
https://doi.org/10.1021/acsabm.9b01035
17. Popescu Din IM, Balas M, Hermenean A, Vander Elst L, Laurent S, Burtea C, Cinteza LO, Dinischiotu A (2020) Novel polymeric micelles−coated magnetic nanoparticles for in vivo bioimaging of liver: toxicological proﬁle and contrast enhancement. Materials 13(12):2722.
https://doi.org/10.3390/ma13122722
18. Shrestha S, Shrestha BK, Ko SW, Kandel R, Park CH, Kim CS (2021) Engineered cellular microenvironments from functionalized multiwalled carbon nanotubes integrating Zein/ Chitosan@ Polyurethane for bone cell regeneration. Carbohydr Polym 251:117035.
https://
doi.org/10.1016/j.carbpol.2020.117035
19. McKernan P, Virani NA, Faria GN, Karch CG, Silvy RP, Resasco DE, Thompson LF, Harrison RG (2021) Targeted single−walled carbon nanotubes for photothermal therapy combined with immune checkpoint inhibition for the treatment of metastatic breast cancer. Nanoscale Res Lett 16(1):1–9.
https://doi.org/10.1186/s11671−020−03459−x
20. Ershadi N, Safaiee R, Golshan M (2021) Functionalized (4, 0) or (8, 0) SWCNT as novel carriers of the anticancer drug 5−FU; A ﬁrst−principle investigation. Appl Surf Sci 536:147718.
https://doi.org/10.1016/j.apsusc.2020.147718
21. Grechkin YA, Grechkina SL, Zaripov EA, Fedorenko SV, Mustaﬁna AR, Berezovski MV (2022) Aptamer−conjugated Tb (III)−doped silica nanoparticles for luminescent detection of leukemia cells. Biomedicines 8(1):14.
https://doi.org/10.3390/biomedicines8010014
22. Gubala V, Giovannini G, Kunc F, Monopoli MP, Moore CJ (2020) Dye−doped silica nanopar− ticles: synthesis, surface chemistry and bioapplications. Cancer Nano 11(1):1–43.
https://doi.
org/10.1186/s12645−019−0056−x
23. Wang L, Xie S, Wang Z, Liu F, Yang Y, Tang C, Wu X, Liu P, Li Y, Saiyin H, Zheng S (2020) Functionalized helical ﬁbre bundles of carbon nanotubes as electrochemical sensors for long− term in vivo monitoring of multiple disease biomarkers. Nat Biomed Eng 4(2):159–171.
https://doi.org/10.1038/s41551−019−0462−8
24. Takeuchi T, Iizumi Y, Yudasaka M, Kizaka−Kondoh S, Okazaki T (2019) Characterization and biodistribution analysis of oxygen−doped single−walled carbon nanotubes used as in vivo ﬂuorescence imaging probes. Bioconjugate Chem 30(5):1323–1330.
https://doi.org/10.1021/
acs.bioconjchem.9b00088
25. Chio L, Pinals RL, Murali A, Goh NS, Landry MP (2020) Covalent surface modiﬁcation effects on single−walled carbon nanotubes for targeted sensing and optical imaging. Adv Funct Mater 30(17):1910556.
https://doi.org/10.1002/adfm.201910556

26 V. G. S. S. Jyothi et al.
26. Wang K, Shang F, Chen D, Cao T, Wang X, Jiao J, He S, Liang X (2021) Protein liposomes−
mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy. J
Nanobiotechnol 19(1):1–15.
https://doi.org/10.1186/s12951−021−00777−9
27. Francian A, Widmer A, Olsson T, Ramirez M, Heald D, Rasic K, Adams L, Martinson H, Kullberg M (2021) Delivery of toll−like receptor agonists by complement C3−targeted liposomes activates immune cells and reduces tumor growth. J Drug Target 29(7):754–760.
https://doi.org/10.1080/1061186X.2021.1878364
28. Andrade RG, Reis B, Costas B, Lima SAC, Reis S (2021) Modulation of macrophages M1/M2 polarization using carbohydrate−functionalized polymeric nanoparticles. Polymers 13(1):88.
https://doi.org/10.3390/polym13010088
29. Treekoon J, Chansaenpak K, Tumcharern G, Zain ZSZ, Lee HB, Kue CS, Kamkaew A (2021) Aza−BODIPY encapsulated polymeric nanoparticles as effective nanodelivery system for photodynamic cancer treatment. Mater Chem Front 5(5):2283–2293.
https://doi.org/10.1039/
D0QM00891E
30. Okpalugo T, Papakonstantinou P, Murphy H, McLaughlin J, Brown N (2005) High resolution
XPS characterization of chemical functionalised MWCNTs and SWCNTs. Carbon 43(1):153–
161. https://doi.org/10.1016/j.carbon.2004.08.033
31. Bandi R, Tummala S, Dadigala R, Alle M, Lee S−H (2022) Role of metal−doped carbon dots in bioimaging and cancer therapy. Smart nanomaterials in biomedical applications. Springer, pp 101–123.
https://doi.org/10.1007/978−3−030−84262−8_4
32. Dadigala R, Bandi R, Alle M, Gangapuram BR, Lee S−H (2022) Graphene−based smart nanomaterials for photothermal therapy. Smart nanomaterials in biomedical applications. Springer, pp 125–153
33. Liu Z, Tabakman S, Welsher K, Dai H (2009) Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. Nano Res 2(2):85–120.
https://doi.
org/10.1007/s12274−009−9009−8
34. Zhang Y, Ali SF, Dervishi E, Xu Y, Li Z, Casciano D, Biris AS (2010) Cytotoxicity effects of graphene and single−wall carbon nanotubes in neural phaeochromocytoma−derived PC12 cells. ACS Nano 4(6):3181–3186.
https://doi.org/10.1021/nn1007176
35. Abidin MN, Goh PS, Ismail AF, Othman MH, Hasbullah H, Said N, Kadir SH, Kamal F, Abdullah MS, Ng BC (2017) Development of biocompatible and safe polyethersulfone hemodialysis membrane incorporated with functionalized multi−walled carbon nanotubes. Mater Sci Eng C 77:572–582.
https://doi.org/10.1016/j.msec.2017.03.273
36. Mostafavi E, Iravani S, Varma RS, Khatami M, Rahbarizadeh F (2022) Eco−friendly synthesis of carbon nanotubes and their cancer theranostic applications. Mater Adv 3(12):4765–4782.
https://doi.org/10.1039/D2MA00341D
37. Kohls A, Maurer Ditty M, Dehghandehnavi F, Zheng S−Y (2022) Vertically aligned carbon nanotubes as a unique material for biomedical applications. ACS Appl Mater Interfaces 14(5):6287–6306.
https://doi.org/10.1021/acsami.1c20423
38. Fu C, Liu T, Li L, Liu H, Chen D, Tang F (2013) The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes. Biomaterials 34(10):2565–2575.
https://doi.org/10.1016/j.biomaterials.2012.12.043
39. Liu T, Li L, Teng X, Huang X, Liu H, Chen D, Ren J, He J, Tang F (2011) Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice. Biomaterials 32(6):1657–1668.
https://doi.org/10.1016/j.biomaterials.2010.10.035
40. Rahman I, Vejayakumaran P, Sipaut C, Ismail J, Chee C (2009) Size−dependent physicochem− ical and optical properties of silica nanoparticles. Mater Chem Phys 114(1):328–332.
https://
doi.org/10.1016/j.matchemphys.2008.09.068
41. Choi JY, Gupta B, Ramasamy T, Jeong JH, Jin SG, Choi HG, Yong CS, Kim JO (2018) PEGylated polyaminoacid−capped mesoporous silica nanoparticles for mitochondria−targeted delivery of celastrol in solid tumors. Colloids Surf B Biointerfaces 165:56–66.
https://doi.org/
10.1016/j.colsurfb.2018.02.015
42. Peng F, Su Y, Zhong Y, Fan C, Lee S−T, He Y (2014) Silicon nanomaterials platform for bioimaging, biosensing, and cancer therapy. Acc Chem Res 47(2):612–623.
https://doi.org/
10.1021/ar400221g

Basic Principles of Functional Materials for Biomedical Applications 27
43. Di Paola M, Quarta A, Conversano F, Sbenaglia EA, Bettini S, Valli L, Casciaro S (2017)
Human hepatocarcinoma cell targeting by glypican−3 ligand peptide functionalized silica
nanoparticles: implications for ultrasound molecular imaging. Langmuir 33(18):4490–4499.
https://doi.org/10.1021/acs.langmuir.7b00327
44. Ekimov A, Onuschenko A (1981) The quantum size effect in three−dimensional microscopic semiconductors. JETP Lett 34(6):363
45. Zrazhevskiy P, Sena M, Gao X (2010) Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. Chem Soc Rev 39(11):4326–4354.
https://doi.org/
10.1039/B915139G
46. Schiffman JD, Balakrishna RG (2018) Quantum dots as ﬂuorescent probes: Synthesis, surface chemistry, energy transfer mechanisms, and applications. Sens Actuators B Chem 258:1191– 1214.
https://doi.org/10.1016/j.snb.2017.11.189
47. Bandi R, Alle M, Dadigala R, Park CW, Han SY, Kwon GJ, Kim JC, Lee SH (2022) Inte− grating the high peroxidase activity of carbon dots with easy recyclability: immobilization on dialdehyde cellulose nanoﬁbrils and cholesterol detection. Appl Mater Today 26:101286.
https://doi.org/10.1016/j.apmt.2021.101286
48. Pankhurst Q, Thanh N, Jones S, Dobson J (2009) Progress in applications of magnetic nanopar− ticles in biomedicine. J Phys D: Appl Phys 42(22):224001.
https://doi.org/10.1088/0022−
3727/42/22/220301
49. Schladt TD, Schneider K, Schild H, Tremel W (2011) Synthesis and bio−functionalization of magnetic nanoparticles for medical diagnosis and treatment. Dalton Trans 40(24):6315–6343.
https://doi.org/10.1039/C0DT00689K
50. Dash S, Das T, Patel P, Panda PK, Suar M, Verma SK (2022) Emerging trends in the nanomedicine applications of functionalized magnetic nanoparticles as novel therapies for acute and chronic diseases. Nanobiotechnol 20(1):1–24.
https://doi.org/10.1186/s12951−022−
01595−3
51. Riaz MK, Riaz MA, Zhang X, Lin C, Wong KH, Chen X, Zhang G, Lu A, Yang Z (2018) Surface functionalization and targeting strategies of liposomes in solid tumor therapy: a review. Int J Mol Sci 19(1):195.
https://doi.org/10.3390/ijms19010195
52. Borrajo ML, Alonso MJ (2022) Using nanotechnology to deliver biomolecules from nose to brain—peptides, proteins, monoclonal antibodies and RNA. Drug Deliv Transl Res 1–19
https://doi.org/10.1007/s13346−021−01086−2
53. Wang X, Wu J, Liu X, Tang K, Cheng L, Li J, Tang Y, Song X, Wang X, Li C (2021)
Engineered liposomes targeting the gut–CNS Axis for comprehensive therapy of spinal cord
injury. J Control Release 331:390–403. https://doi.org/10.1016/j.jconrel.2021.01.032
54. Madhusudhan A (2018) The effect of colon targeted delivery of celecoxib loaded microspheres on experimental colitis induced by acetic acid in rats. Asian J Pharm (AJP) 12(01).
https://
doi.org/10.22377/ajp.v12i01.1919
55. Subbiah R, Veerapandian M, Subbiah R, Yun K (2010) Nanoparticles: functionalization and multifunctional applications in biomedical sciences. Curr Med Chem 17(36):4559–4577.
https://doi.org/10.2174/092986710794183024
56. Antonucci A, Kupis−Rozmysłowicz J, Boghossian AA (2017) Noncovalent protein and peptide functionalization of single−walled carbon nanotubes for biodelivery and optical sensing applications. ACS Appl Mater Interfaces 9(13):11321–11331.
https://doi.org/10.
1021/acsami.7b00810
57. Bai L, Bai Y, Zheng J (2017) Improving the ﬁller dispersion and performance of silicone rubber/multi−walled carbon nanotube composites by noncovalent functionalization of poly− methylphenylsiloxane. J Mater Sci 52(12):7516–7529.
https://doi.org/10.1007/s10853−017−
0984−y
58. Mittal V (2011) Carbon nanotubes surface modiﬁcations: an overview Surface modiﬁcation of nanotube ﬁllers. Wiley Online Library
59. O’connell MJ, Bachilo SM, Huffman CB, Moore VC, Strano MS, Haroz EH, Rialon KL, Boul PJ, Noon WH, Kittrell C, Ma J (2002) Band gap ﬂuorescence from individual single−walled carbon nanotubes. Science 297(5581):593–596.
https://doi.org/10.1126/science.1072631

28 V. G. S. S. Jyothi et al.
60. Moore VC, Strano MS, Haroz EH, Hauge RH, Smalley RE, Schmidt J, Talmon Y (2003)
Individually suspended single−walled carbon nanotubes in various surfactants. Nano Lett
3(10):1379–1382.
https://doi.org/10.1021/nl034524j
61. Daniel S, Rao TP, Rao KS, Rani SU, Naidu G, Lee H−Y, Kawai T (2007) A review of DNA functionalized/grafted carbon nanotubes and their characterization. Sens Actuators B Chem 122(2):672–682.
https://doi.org/10.1016/j.snb.2006.06.014
62. Gao Y, Kyratzis I (2008) Covalent immobilization of proteins on carbon nanotubes using the cross−linker 1−ethyl−3−(3−dimethylaminopropyl) carbodiimide—a critical assessment. Bioconjugate Chem 19(10):1945–1950.
https://doi.org/10.1021/bc800051c
63. Oh SJ, Lee HJ, Keum DK, Lee SW, Wang DH, Park SY, Tan LS, Baek JB (2006) Multiwalled carbon nanotubes and nanoﬁbers grafted with polyetherketones in mild and viscous polymeric acid. Polymer 47(4):1132–1140.
https://doi.org/10.1016/j.polymer.2005.12.064
64. Prato M, Kostarelos K, Bianco A (2008) Functionalized carbon nanotubes in drug design and discovery. Acc Chem Res 41(1):60–68.
https://doi.org/10.1021/ar700089b
65. Carrero−Sanchez J, Elias A, Mancilla R, Arrellin G, Terrones H, Laclette J, Terrones M (2006) Biocompatibility and toxicological studies of carbon nanotubes doped with nitrogen. Nano Lett 6(8):1609–1616.
https://doi.org/10.1021/nl060548p
66. Abuilaiwi FA, Laoui T, Al−Harthi M, Atieh MA (2010) Modiﬁcation and functionalization of multiwalled carbon nanotube (MWCNT) via ﬁscher esteriﬁcation. Arab J Sci Eng 35(1):37–48
67. Cha BG, Kim J (2019) Functional mesoporous silica nanoparticles for bio−imaging applica− tions. Wiley Interdiscip Rev Nanomed Nanobiotechnol 11(1):e1515.
https://doi.org/10.1002/
wnan.1515
68. Rosenholm JM, Sahlgren C, Lindén M (2010) Towards multifunctional, targeted drug delivery systems using mesoporous silica nanoparticles–opportunities and challenges. Nanoscale 2(10):1870–1883.
https://doi.org/10.1039/C0NR00156B
69. Liberman A, Mendez N, Trogler WC, Kummel AC (2014) Synthesis and surface functional− ization of silica nanoparticles for nanomedicine. Surf Sci Rep 69(2–3):132–158.
https://doi.
org/10.1016/j.surfrep.2014.07.001
70. Banga R, Yarwood J, Morgan AM, Evans B, Kells J (1995) FTIR and AFM studies of the kinetics and self−assembly of alkyltrichlorosilanes and (perﬂuoroalkyl) trichlorosilanes onto glass and silicon. Langmuir 11(11):4393–4399.
https://doi.org/10.1021/la00011a036
71. Hermanson GT (2013) Bioconjugate techniques. Academic press.
72. Galdino FE, Picco AS, Sforca ML, Cardoso MB, Loh W (2020) Effect of particle functional− ization and solution properties on the adsorption of bovine serum albumin and lysozyme onto silica nanoparticles. Colloids Surf B: Biointerfaces 186:110677.
https://doi.org/10.1016/j.col
surfb.2019.110677
73. Huh S, Wiench JW, Yoo J−C, Pruski M, Lin VS−Y (2003) Organic functionalization and morphology control of mesoporous silicas via a co−condensation synthesis method. Chem Mater 15(22):4247–4256.
https://doi.org/10.1021/cm0210041
74. Gottuso A, Armetta F, Cataldo A, Nardo VM, Parrino F, Saladino ML (2022) Func− tionalization of mesoporous silica nanoparticles through one−pot co−condensation in w/o emulsion. Microporous Mesoporous Mater 335:111833.
https://doi.org/10.1016/j.micromeso.
2022.111833
75. Bagwe RP, Hilliard LR, Tan W (2006) Surface modiﬁcation of silica nanoparticles to reduce aggregation and nonspeciﬁc binding. Langmuir 22(9):4357–4362.
https://doi.org/10.1021/la0
52797j
76. Buchman YK, Lellouche E, Zigdon S, Bechor M, Michaeli S, Lellouche J−P (2013) Silica nanoparticles and polyethyleneimine (PEI)−mediated functionalization: a new method of PEI covalent attachment for siRNA delivery applications. Bioconjug Chem 24(12):2076–2087.
https://doi.org/10.1021/bc4004316
77. Sperling RA, Parak WJ (2010) Surface modiﬁcation, functionalization and bioconjugation of colloidal inorganic nanoparticles. Philos Trans Math Phys Eng Sci 368(1915):1333–1383.
https://doi.org/10.1098/rsta.2009.0273

Basic Principles of Functional Materials for Biomedical Applications 29
78. Thanh NT, Green LA (2010) Functionalisation of nanoparticles for biomedical applications.
Nano Today 5(3):213–230. https://doi.org/10.1016/j.nantod.2010.05.003
79. Snee PT (2018) The role of colloidal stability and charge in functionalization of aqueous quantum dots. Acc Chem Res 51(11):2949–2956.
https://doi.org/10.1021/acs.accounts.8b0
0405
80. Graf C, Dembski S, Hofmann A, Rühl E (2006) A general method for the controlled embedding of nanoparticles in silica colloids. Langmuir 22(13):5604–5610.
https://doi.org/10.1021/la0
60136w
81. Mattoussi H, Mauro JM, Goldman ER, Anderson GP, Sundar VC, Mikulec FV, Bawendi MG (2000) Self−assembly of CdSe
recombinant protein. J Am Chem Soc 122(49):12142–12150.
https://doi.org/10.1021/ja0
02535y
82. Uyeda HT, Medintz IL, Jaiswal JK, Simon SM, Mattoussi H (2005) Synthesis of compact multidentate ligands to prepare stable hydrophilic quantum dot ﬂuorophores. JACS 127(11):3870–3878.
https://doi.org/10.1021/ja044031w
83. Bera D, Qian L, Tseng T−K, Holloway PH (2010) Quantum dots and their multimodal applications: a review. Materials 3(4):2260–2345.
https://doi.org/10.3390/ma3042260
84. Ong W−L, Rupich SM, Talapin DV, McGaughey AJ, Malen JA (2013) Surface chemistry mediates thermal transport in three−dimensional nanocrystal arrays. Nature Mater 12(5):410– 415.
https://doi.org/10.1038/nmat3596
85. Hammer NI, Emrick T, Barnes MD (2007) Quantum dots coordinated with conjugated organic ligands: new nanomaterials with novel photophysics. Nanoscale Res Lett 2(6):282.
https://
doi.org/10.1007/s11671−007−9062−8
86. Mei BC, Susumu K, Medintz IL, Delehanty JB, Mountziaris T, Mattoussi H (2008) Modular poly (ethylene glycol) ligands for biocompatible semiconductor and gold nanocrystals with extended pH and ionic stability. J Mater Chem 18(41):4949–4958.
https://doi.org/10.1039/
B810488C
87. Olsson C (2009) Synthesis of bifunctional poly (ethylene oxides) and their use as ligands to nanoparticles (Doctoral dissertation, Staats−und Universitätsbibliothek Hamburg Carl von Ossietzky)
88. Zhang Y, Clapp A (2011) Overview of stabilizing ligands for biocompatible quantum dot nanocrystals. Sensors 11(12):11036–11055.
https://doi.org/10.3390/s111211036
89. Correa−Duarte MA, Kobayashi Y, Caruso RA, Liz−Marzán LM (2001) Photodegradation of SiO2−coated CdS nanoparticles within silica gels. J Nanosci Nanotechnol 1(1):95–99.
https://
doi.org/10.1166/jnn.2001.010
90. Nann T, Riegler J, Nick P, Mulvaney P (2005) Quantum dots with silica shells. Paper presented at the nanobiophotonics and biomedical applications II, vol 5705. pp 77–84.
https://doi.org/
10.1117/12.582871
91. Beloglazova NV, Shmelin PS, Speranskaya ES, Lucas B, Helmbrecht C, Knopp D, Niessner R, De Saeger S, Goryacheva IY (2013) Quantum dot loaded liposomes as ﬂuorescent labels for immunoassay. Anal Chem 85(15):7197–7204.
https://doi.org/10.1021/ac401729y
92. Fernández−Argüelles M, Costa−Fernández JM, Pereiro R, Sanz−Medel A (2008) Simple bio−conjugation of polymer−coated quantum dots with antibodies for ﬂuorescence−based immunoassays. Analyst 133(4):444–447.
https://doi.org/10.1039/B802360N
93. Shen L (2011) Biocompatible polymer/quantum dots hybrid materials: current status and future developments. J Funct Biomater 2(4):355–372.
https://doi.org/10.3390/jfb2040355
94. Ciobanu M, Heurtault B, Schultz P, Ruhlmann C, Muller C, Frisch B (2007) Layersome:
development and optimization of stable liposomes as drug delivery system. Int J Pharm 344(1–
2):154–157. https://doi.org/10.1016/j.ijpharm.2007.05.037
95. Banerjee A, Grazon C, Nadal B, Pons T, Krishnan Y, Dubertret B (2015) Fast, efﬁcient, and stable conjugation of multiple DNA strands on colloidal quantum dots. Bioconjug Chem 26(8):1582–1589.
https://doi.org/10.1021/acs.bioconjchem.5b00221
96. DeLong RK, Reynolds CM, Malcolm Y, Schaeffer A, Severs T, Wanekaya A (2010) Func− tionalized gold nanoparticles for the binding, stabilization, and delivery of therapeutic DNA,

30 V. G. S. S. Jyothi et al.
RNA, and other biological macromolecules. Nanotechnol Sci Appl 3:53. https://doi.org/10.
2147/NSA.S8984
97. Clapp AR, Medintz IL, Mattoussi H (2006) Förster resonance energy transfer investigations
using quantum−dot ﬂuorophores. ChemPhysChem 7(1):47–57. https://doi.org/10.1002/cphc.
200500217
98. Algar WR, Krull UJ (2010) Developing mixed ﬁlms of immobilized oligonucleotides and quantum dots for the multiplexed detection of nucleic acid hybridization using a combination of ﬂuorescence resonance energy transfer and direct excitation of ﬂuorescence. Langmuir 26(8):6041–6047.
https://doi.org/10.1021/la903751m
99. Algar WR, Krull UJ (2011) Interfacial chemistry and the design of solid−phase nucleic acid hybridization assays using immobilized quantum dots as donors in ﬂuorescence resonance energy transfer. Sensors 11(6):6214–6236.
https://doi.org/10.3390/s110606214
100. Xiao Q, Huang S, Qi Z−D, Zhou B, He Z−K, Liu Y (2008) Conformation, thermodynamics and stoichiometry of HSA adsorbed to colloidal CdSe/ZnS quantum dots. BBA Proteins Proteomics 1784(7–8):1020–1027.
https://doi.org/10.1016/j.bbapap.2008.03.018
101. Pereira M, Lai EP (2008) Capillary electrophoresis for the characterization of quantum dots after non−selective or selective bioconjugation with antibodies for immunoassay. J
Nanobiotechnol 6(1):1–15.
https://doi.org/10.1186/1477−3155−6−10
102. Kairdolf BA, Smith AM, Stokes TH, Wang MD, Young AN, Nie S (2013) Semiconductor quantum dots for bioimaging and biodiagnostic applications. Annu Rev Anal Chem 6:143– 162.
https://doi.org/10.1146/annurev−anchem−060908−155136
103. Koolpe M, Burgess R, Dail M, Pasquale EB (2005) EphB receptor−binding peptides identi− ﬁed by phage display enable design of an antagonist with ephrin−like afﬁnity. J Biol Chem 280(17):17301–17311.
https://doi.org/10.1074/jbc.M500363200
104. Wolcott A, Gerion D, Visconte M, Sun J, Schwartzberg A, Chen S, Zhang JZ (2006) Silica− coated CdTe quantum dots functionalized with thiols for bioconjugation to IgG proteins. J Phys Chem B 110(11):5779–5789.
https://doi.org/10.1021/jp057435z
105. Derfus AM, Chen AA, Min D−H, Ruoslahti E, Bhatia SN (2007) Targeted quantum dot conjugates for siRNA delivery. Bioconjug Chem 18(5):1391–1396.
https://doi.org/10.1021/
bc060367e
106. Kolb HC, Sharpless KB (2003) The growing impact of click chemistry on drug discovery. Drug Discovery Today 8(24):1128–1137.
https://doi.org/10.1016/S1359−6446(03)02933−7
107. Nwe K, Brechbiel MW (2009) Growing applications of “click chemistry” for bioconjugation in contemporary biomedical research. Cancer Biother Radiopharm 24(3):289–302.
https://
doi.org/10.1089/cbr.2008.0626
108. Huisgen R (1963) Kinetics and mechanism of 1, 3−dipolar cycloadditions. Angew Chem Int Ed 2(11):633–645.
https://doi.org/10.1002/anie.196306331
109. Speers AE, Cravatt BF (2004) Proﬁling enzyme activities in vivo using click chemistry methods. Chem Biol 11(4):535–546.
https://doi.org/10.1016/j.chembiol.2004.03.012
110. Al−Saadi A, Yu CH, Khutoryanskiy VV, Shih S−J, Crossley A, Tsang SC (2009) Layer−by− layer electrostatic entrapment of protein molecules on superparamagnetic nanoparticle: a new strategy to enhance adsorption capacity and maintain biological activity. J Phys Chem C
113(34):15260–15265.
https://doi.org/10.1021/jp903100j
111. Sun B, Zhang Y, Gu K−J, Shen Q−D, Yang Y, Song H (2009) Layer−by−layer assembly of conjugated polyelectrolytes on magnetic nanoparticle surfaces. Langmuir 25(10):5969–5973.
https://doi.org/10.1021/la804217w
112. Xie J, Peng S, Brower N, Pourmand N, Wang SX, Sun S (2006) One−pot synthesis of monodisperse iron oxide nanoparticles for potential biomedical applications. Pure Appl Chem 78(5):1003–1014.
https://doi.org/10.1351/pac200678051003
113. Jun YW, Huh YM, Choi JS, Lee JH, Song HT, Kim S, Yoon S, Kim KS, Shin JS, Suh JS, Cheon J (2005) Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J Am Chem Soc 127(16):5732–5733.
https://doi.
org/10.1021/ja0422155

Basic Principles of Functional Materials for Biomedical Applications 31
114. Patil R, Thorat N, Shete P, Otari S, Tiwale B, Pawar S (2016) In vitro hyperthermia with
improved colloidal stability and enhanced SAR of magnetic core/shell nanostructures. Mater
Sci Eng C 59:702–709.
https://doi.org/10.1016/j.msec.2015.10.064
115. Xu C, Xu K, Gu H, Zheng R, Liu H, Zhang X, Guo Z, Xu B (2004) Dopamine as a robust anchor to immobilize functional molecules on the iron oxide shell of magnetic nanoparticles. J Am Chem Soc 126(32):9938–9939.
https://doi.org/10.1021/ja0464802
116. Shin J, Anisur RM, Ko MK, Im GH, Lee JH, Lee IS (2009) Hollow manganese oxide nanopar− ticles as multifunctional agents for magnetic resonance imaging and drug delivery. Angew Chem Int Ed 48(2):321–324.
https://doi.org/10.1002/anie.200802323
117. Huang A, Huang L, Kennel SJ (1980) Monoclonal antibody covalently coupled with fatty acid. A reagent for in vitro liposome targeting. J Biol Chem 255(17):8015–8018.
https://doi.
org/10.1016/S0021−9258(19)70595−X
118. Torchilin V, Klibanov A, Smirnov V (1982) Phosphatidylinositol may serve as the hydrophobic anchor for immobilization of proteins on liposome surface. FEBS Lett 138(1):117–120.
https://doi.org/10.1016/0014−5793(82)80408−0
119. Harsch M, Walther P, Weder H, Hengartner H (1981) Targeting of monoclonal antibody− coated liposomes to sheep red blood cells. Biochem Biophys Res Commun 103(3):1069–1076.
https://doi.org/10.1016/0006−291X(81)90917−7
120. Torchilin V, Omel’Yanenko V, Klibanov A, Mikhailov A, Gol’danskII V, Smirnov V (1980) Incorporation of hydrophilic protein modiﬁed with hydrophobic agent into lipo− some membrane. BBA−Biomembranes 602(3):511–521.
https://doi.org/10.1016/0005−273
6(80)90330−2
121. Chua M−M, Fan S−T, Karush F (1984) Attachment of immunoglobulin to liposomal membrane via protein carbohydrate. Biochim Biophys Acta Gen Subj 800(3):291–300.
https://doi.org/
10.1016/0304−4165(84)90408−2
122. Hansen CB, Kao GY, Moase EH, Zalipsky S, Allen TM (1995) Attachment of antibodies to sterically stabilized liposomes: evaluation, comparison and optimization of coupling proce− dures. Biochim Biophys Acta Biomembr 1239(2):133–144.
https://doi.org/10.1016/0005−273
6(95)00138−S
123. Nässander UK, Steerenberg PA, Poppe H, Storm G, Poels LG, De Jong WH, Crommelin DJ (1992) In vivo targeting of OV−TL 3 immunoliposomes to ascitic ovarian carcinoma cells (OVCAR−3) in athymic nude mice. Cancer Res 52(3):646–653
124. Huang L, Kennel SJ (1979) Binding of immunoglobulin G to phospholipid vesicles by sonication. Biochemistry 18(9):1702–1707.
https://doi.org/10.1021/bi00576a011
125. Leserman LD, Weinstein JN, Moore JJ, Terry WD (1980) Speciﬁc interaction of myeloma tumor cells with hapten−bearing liposomes containing methotrexate and carboxyﬂuorescein. Cancer Res 40(12):4768–4774.
http://www.ncbi.nlm.nih.gov/pubmed/7438109
126. Illum L, Jones P, Kreuter J, Baldwin R, Davis S (1983) Adsorption of monoclonal antibodies to polyhexylcyanoacrylate nanoparticles and subsequent immunospeciﬁc binding to tumour cells in vitro. Int J Pharm 17(1):65–76.
https://doi.org/10.1016/0378−5173(83)90019−4
127. Li Y, Ogris M, Wagner E, Pelisek J, Rüffer M (2003) Nanoparticles bearing polyethyleneglycol−coupled transferrin as gene carriers: preparation and in vitro evaluation.
Int J Pharm 259(1–2):93–101.
https://doi.org/10.1016/S0378−5173(03)00211−4
128. Gautier S, Grudzielski N, Gofﬁnet G, De Hassonville SH, Delattre L, Jérôme R (2001) Prepa− ration of poly (D, L−lactide) nanoparticles assisted by amphiphilic poly (methyl methacrylate− co−methacrylic acid) copolymers. J Biomater Sci Polym Ed 12(4):429–450.
https://doi.org/
10.1163/156856201750195306

Functional Biomaterials for Targeted
Drug Delivery Applications
Hemant Singh, Muzammil Kuddushi, Ramesh Singh, Sneha Sathapathi,
Aniruddha Dan, Narayan Chandra Mishra, Dhiraj Bhatia,
and Mukesh Dhanka
Abstract the absorption and biodistribution of small molecules and biologics at the targeted diseased sites to maximize therapeutic performances without affecting the healthy
cells of the tissue or organ inside the body. For this purpose, it is essential to select effective biomaterial-based platforms that can release drugs in a sustained manner
without altering their bioactivity and causing toxic effects in off-targeted tissues. Such biomaterials can be directly implanted/injected into the targeted diseased area of the body to enhance drug delivery efﬁciency. Various materials have been explored
to fabricate targeted drug delivery systems. Functional biomaterials with desired physicochemical and biological properties are getting colossal attention because they can respond to their environmental cues, such as ﬂuctuations in pH, temper-
ature, or cell-associated enzymatic activity, and improve drug delivery integration and tissue regeneration. This chapter explores the progress of different approaches in functionalizing polymeric, metallic, and ceramic biomaterials for targeted drug
delivery systems.
Keywords ·Biomaterials ·Functionalized polymer ·
Functionalized metals and ceramics
H. Singh (B) · (B)
Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar,
Gandhinagar, Gujarat, India
e-mail: [email protected]
M. Dhanka e-mail:
[email protected]
M. Kuddushi
Department of Chemical and Materials Engineering, University of Alberta, Alberta, Canada
N. C. Mishra
Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2024 A. Madhusudhan et al. (eds.), and Their Theranostics Approaches
https://doi.org/10.1007/978-981-99-6597-7_2
33

34
1 Introduction
Drug delivery is the process of delivering drugs to humans or animals to achieve a
desirable therapeutic effect in treating illnesses [1]. Various drug delivery systems
(e.g., tablets, capsules, syrups, ointments, and among others) have been developed
and tested for therapeutics molecule delivery [1, 35]. However, these traditional drug
delivery technologies are ineffective in providing a sustained drug release proﬁle and
suffer from low bioavailability and rapid ﬂuctuation in plasma drug levels [1, 35].
Thus, the entire treatment procedure may be ineffective without an effective delivery method [
35, 118]. Moreover, the drug must be administered at an actual controlled
rate and at the target site to provide optimal efﬁcacy and safety [35, 118]. Therefore,
properly designed targeted drug delivery systems with controlled drug release are being developed to address the issues with traditional drug delivery technologies [
5,
35, 65, 79, 118]. Presently, there is a high demand for developing effective targeted
therapeutic delivery systems to reduce dosage frequency and boost drug efﬁciency at the required site to minimize its adverse side effects [
118]. A collaborative effort
by engineers, chemists, biologists, clinicians, and biomaterial scientists who have been using biomaterial for fabricating the targeted drug delivery system for speciﬁc cells has sparked a surge in interest in improving human health [
1, 35, 118]. Various
pharmacological substances, including antibodies, peptides, vaccines, drugs, and enzymes, have increased delivery and effectiveness thanks to the development of biomaterials-based targeted drug delivery systems [
99]. Biomaterials are generally
grouped into three classes: metals, ceramics, and polymers [1]. These biomaterials
have been used as a carrier, and many of these materials with combinations have been created to release medicines over long periods of time [
51, 58, 77, 78, 99].
They may be further customized to target certain cells/tissues of the body [99].
This phenomenon allows the reduction of dosage of pharmaceutical drugs while still huge gap in achieving the desired therapeutic effect and lowering patient toxicity
[
99]. An overview of available possibilities in the polymers, metals, and ceramics
for fabricating targeted drug delivery systems has shown in Fig. 1, and this chapter
explores the progress of different approaches in functionalizing polymeric, metallic, and ceramic biomaterials for the application in targeted drug delivery.
2 Functionalization of Polymeric Materials for Targeted
Drug Delivery
The use of polymers and polymer-based nanomaterials in the biomedical ﬁeld has risen dramatically in recent years [
3, 35]. Identifying and understanding the intended
applications that call for modifying these materials is crucial before designing or
selecting polymers and their nanocomposites [35, 118]. Speciﬁc moieties and conju-
gated compounds that enhance material performance can be grafted onto polymers
through chemical functionalization [1]. Since a wide range of inert polymers and

Functional Biomaterials for Targeted Drug Delivery Applications 35
Fig. 1
available possibilities in the
polymers, metals, and
ceramics for fabricating
targeted drug delivery
systems
nanomaterials are commercially available, surface modiﬁcation is a necessary step to
increase their adherence and enable the development of these materials for special-
ized applications across a variety of sectors [35, 76, 99]. The properties of poly-
meric materials are typically determined by functional groups other than the back-
bone chains [35, 99]. Metal coordination is a type of noncovalent bond that has
been employed in the functionalization of supramolecular polymers [35, 99]. Since
numerous pyridine-based ligands are commercially accessible and can structurally
be changed, pyridyl-based systems have a high probability of success as polymer-
izable metal complexes and polymers functionalized by metal coordination [118].
Bipyridines and terpyridines in particular are appealing because they may act as
acceptors to maintain different metal oxidation states and are well known for coordi-
nating a range of metals [118]. For example, hyaluronic acid derivatives were func-
tionalized by the maleic anhydride ring opening process by reacting with awaiting
hydroxyl groups [99, 118]. One such promising application of the functionalization
of polymeric materials is the usage of the same for targeted drug delivery [1, 118].
For fabricating the drug delivery systems, the immobilization of bioactive substances on a polymeric surface through physical adsorption, i.e., noncovalent interactions, is
desirable [
1, 118]. These variations are crucial, especially for various drug delivery
methods that are intended to deliver an adequate amount of medication to the targeted site while minimizing the adverse impacts of the drugs to the other body organs [
1,
118]. In order to address the limitations of the traditional dosage forms, targeted
and customized drug delivery systems were developed [1, 118]. Moreover, to enable
an effective drug delivery, several materials have been created through employing
nanotechnology techniques in polymeric materials for anticancer drug delivery [5, 6,
100, 107]. Various disciplines are actively developing products using carbon-based
biomaterials and nanomaterials. In the biomedical industry, intensive research is

36
being done to create new carbon nanotubes (CNT) for targeted disease diagnosis and
their treatment [100, 106, 107]. Due to their smaller size (nanometers in diameter and
micrometers in length), which allows them to interact with living biological tissues
thereby improving the efﬁciency of drug delivery. Moreover CNTs also have some
signiﬁcant properties [100, 106, 107] like,
•Biocompatible with a variety of cell types, making them a safe material for use
in drug delivery systems.
•CNTs can be functionalized with speciﬁc targeting molecules, such as antibodies or peptides, to enable targeted delivery of drugs to speciﬁc cells or tissues.
•CNTs can help to stabilize the drugs, protecting them from degradation and increasing their shelf life.
•CNTs can be engineered to release drugs in a controlled manner, which can
improve the efﬁcacy of the drug while reducing potential side effects.
•CNTs have been shown to be nontoxic in low concentrations, making them an
attractive material for use in medical applications.
Therefore, drug delivery systems in the cancer treatment, CNTs can be employed.
Targeted tissue distribution of CNTs via microencapsulation by employing biocom-
patible polymeric membranes like alginate-poly-l-lysine-alginate can be performed
as a part of cancer therapy [100, 106, 107]. To address the issue of intrinsic toxicity of
CNTs, it has been suggested that CNTs covalently functionalized with phenyl-SO
3H
or phenyl (COOH)
2 groups provide less toxicity to cells than raw CNTs treated
with surfactants [
100, 106, 107]. Focusing on CNTs in particular, their low solu-
bility in aqueous media severely hinders their use in almost all biological media
[100]. Therefore, surface functionalization of the CNTs is equally important for their
activity [100]. In addition to resolving the issue of CNTs’ hydrophobic nature, which
can lead to the formation of highly poisonous aggregates, surface functionalization also improves the material’s biocompatibility [
37, 100]. In the area of diagnostic
and imaging, CNTs have another promising powerful use [100]. CNTs have been
used to detect the prostate and colorectal cancer marker, and a hepatocarcinoma marker [
106]. Drugs that could not ordinarily be given to cancer cells by microscale
vehicles can now be supplied to them using a nanoscale vehicle, such as CNTs
mixed with other composites [106]. CNTs are potential needle-like transporters of
macromolecules like genes and proteins as well as tiny medicinal compounds [18,
38]. In the treatment of cancer, single-walled nanotubes (SWNTs) functionalized
by Polyethylene glycol (PEG) and phospholipid, further coupled with the anticancer
paclitaxel (PTX) successful used [73]. SWCNTs, graphene-based nanomaterials, and
their prototypes have also been evaluated for their use in TB and cancer chemotherapy [
105]. It is still essential to concentrate on the metabolism, biodistribution, clearance,
and accumulation of nanomaterials, especially CNTs [100]. Additionally, CNTs have
been discovered to be potential scaffold materials for the bone and nerve tissue regeneration [
13]. By regulating its type, delivery site, and dosage, CNTs can be
a secure, novel, and high-performance biomaterial [13]. Furthermore, cross-linked
polymers known as hydrogels are essential in many biomedical ﬁelds including drug administration, sensor systems, and tissue engineering [
85]. Recent progresses in the

Functional Biomaterials for Targeted Drug Delivery Applications 37
development of magnetic hydrogels as a drug carrier uses the natural polymers like
polysaccharides, protein, and DNA have been documented [85]. According to studies,
adding versatility to the hydrogel formulation by functionalizing PEG chains with
hydrazone groups or chemically orthogonal ester and grafting Rhodamin B (RhB)
allows for the release of the hydrophilic drug mimic load to last for longer [85]. In
terms of drug delivery effectiveness, aggregating norﬂoxacin molecules in hydro-
gels and raising drug concentration both improved drug delivery performance [50].
In a number of soft tissue applications, thermosensitive injectable hydrogels have been employed to administer pharmacological and cellular therapy [
39]. Magnetic
hybrid hydrogels have also been constructed. They mix the magnetic characteristics
of nanoparticles with the usual properties of the hydrogel to enhance the desired prop-
erties [19]. A substantial amount of medication can be put into the hybrid hydrogel
before being administered [19]. Because the hydrogels contain magnetic nanoparti-
cles, the hydrogel can be transferred and localized in the target spot using a magnet [
19]. Therapeutic agent delivery to bladder lesion hope will soon be transformed by
hydrogel-based drug delivery devices. The efﬁcacy of therapy seems to be increased
by combining a variety of treatment modalities based on hydrogels and combina-
torial drug delivery systems with distinct mechanisms of action [102]. This section
focuses on a couple of highly applicable polymeric biomaterials that can be applied to the delivery of certain drugs.
2.1 Functionalized Collagen for Targeted Drug Delivery
The discipline of tissue engineering is currently seeing a revival in the usage of collagen as a biomaterial [
9]. In many different drug delivery systems and biomate-
rial applications, collagen plays a signiﬁcant role [9]. Because it is widely avail-
able and has great biocompatibility and biodegradability qualities, collagen has been frequently used in drug delivery [
9]. The most effective and exciting appli-
cations include mini-pellets containing protein medicines, injectable dispersions for treating local tumors, and sponges carrying antibiotics [
9]. The subcutaneous
injection of soluble collagen for the treatment of dermatological problems has been
one of collagen’s most successful commercial applications [9]. Some instances of
frequently utilized collagen-based delivery vehicles are corneal shields, scaffolds
for various chronic and burn wounds, nanoparticles for gene delivery, growth factor-
loaded injectable hydrogels, and antibiotic dressings [9]. The physical or chemical
cross-linking of collagen modulates biodegradability and drug release to control the impact of drug delivery [
9]. It has been demonstrated that collagen nanoparticles are
thermally stable particles that quickly reach sterilization and work well as carriers for
medicinal substances and cytotoxicity agents [14]. Collagen-based polymeric mate-
rials also exhibit high efﬁcacy in being used as a system for the controlled release of antibiotics/steroids [
14]. In the upcoming years, smart collagen nanoparticles can
direct the growth of in vivo tissues, engage stem cells, and direct them to particular
body regions [14]. It has been reported that thermoresponsive drug delivery vehicles

38
made of elastin-b-collagen-like peptide (ELP-CLP) vesicles can target collagen-
containing matrices, as shown in Fig. 2 [74]. For the targeted therapy of various
diseases like joint problems linked to high collagen remodeling activity, ELP-CLP
vesicles may be viable contenders as drug carriers for such associated problems
[74]. Using collagen in combination with biodegradable hydrophobic polyesters is a
feasible approach for creating therapeutic biomaterials [74]. With the help of these
polymeric materials, additional lipophilic medications supporting tissue repair can be delivered [
74].
Fig. 2
with permission from [74])

Functional Biomaterials for Targeted Drug Delivery Applications 39
2.2 Functionalized Chitosan for Targeted Drug Delivery
Natural cationic biopolymer chitosan was developed by partial deacetylated of chitin
[69]. Chitosan-modiﬁed metallic and polymer scaffolds have been the subject of
extensive research during the past ten years [69]. Chitosan coatings have been created
using a variety of techniques, including electrophoretic deposition, sol–gel processes, dip and spin coating, electrospinning, etc. Chitosan’s surface is functionalized to improve the interaction with the scaffolds. CS-based coatings offer a promising
alternative for promoting successful orthopedic applications [
69]. The synthesis of
chitosan nanoparticles using collagen peptide (CP) is particularly intriguing since the produced nanoparticles found stable under physiological settings, as shown in
Fig.
3a[69]. Such nanoparticles offer a great deal of potential for application as
intelligent drug delivery systems as cutting-edge cancer therapies [69]. In contrast to
chemical processes that change the bulk properties of chitosan, employing collagen in chitosan ﬁlms can preserve the native qualities of chitosan [
10]. Although the creation
of collagen-chitosan ﬁlms and their application in the delivery of drugs have been
previously reported, the fabrication of collagen peptide-chitosan nanoparticles and an
examination of the fundamental bonding mechanisms on the size and morphology of
nanoparticles have not yet been done [
10, 69]. According to a study, the synthesized
chitosan-based polymeric material had good cytocompatibility with 3T3 ﬁbroblast cells [
10]. The pH-controlled release of DOX (a medication) suggests that its potential
for administering antitumor medications is based on the extracellular pH of the tumor
environment. Hence, proper functionalization of chitosan-based polymeric material
encapsulated with other suitable composites results in the better release of antitumor
drugs at the targeted site [
10].
2.3 Functionalized Gelatin for Targeted Drug Delivery
The irreversible denaturation of collagen protein yields gelatin also known as the molecular derivative of collagen [
70]. Gelatin is widely being used in cell and
tissue culture as an alternative of collagen for biomaterial purposes because it has
a molecular structure and function that seem to be remarkably similar to those of
collagen [70]. Gelatin is a frequently utilized natural macromolecule with outstanding
biocompatibility and biodegradability in the biomedical ﬁeld [70]. Nanoparticles-
based drug delivery has drawn signiﬁcant attention among numerous promising new drug delivery methods for the analysis and handling of a number of diseases, and at the moment, several formulations are being used in clinical settings [
81].
Nanoparticles-based drug delivery methods have been created using a variety of biodegradable and biocompatible polymers from both natural and synthetic sources [
81]. By employing exfoliated graphene oxide as a precursor, a straightforward and
environmentally acceptable synthetic method for producing gelatin-functionalized

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CHAPTER XV
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Courts and Procedure.
To do this with any success it will be necessary first to study the
causation of crime, because until you know how it is caused you cannot
possibly frame any system of prevention that is likely to do less harm than
good.
This is a subject that many men have been studying for some years past,
but very little progress has yet been made. The old shibboleths that crime
results from a desire for crime and that the only cure is savage punishment
still hold good with all Governments, though quite discredited outside
official circles. It is a most fascinating subject, and as it is one I have
worked at for many years I may be excused for devoting a somewhat large
space to it here.
It is more than twenty-five years ago that my attention was first attracted
to the causation of crime. I was a young magistrate then, trying my first
cases; very nervous, very conscientious that I should fulfil all the legal
requirements as laid down in the Codes. It had never occurred to me then
that there was any gulf between justice and law—I supposed that they were
one, that law was only codified and systemised justice; therefore, in
fulfilling the Law I thought that I was surely administering Justice.
I was trying a theft case. I cannot remember now what it was that had
been stolen, but I think it was a bullock. The accused was undefended, and
I, as the custom is, questioned him about the case, not with the view of
getting him to commit himself, but in order to try to elicit his defence, if

any. He had none. He admitted the theft, described the circumstances quite
fully and frankly, and said he was guilty. I asked him if he knew when he
took the bullock from the grazing ground that he was stealing it, and he
answered "Yes." I asked him if he knew that the punishment for cattle theft
was two years' imprisonment, which practically meant ruin for life, and he
replied that he knew it would be heavy.
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He moved uneasily in the dock without answering, looked about him,
and seemed puzzled.
I repeated the question.
Evidently he was trying to remember back why he had done it, and
found it difficult. He had not considered the point before, and introspection
was new to him. "Why did I do it?" he was saying to himself.
"Well?" I asked.
He looked me frankly in the face. "I don't know," he said. "I suppose I
could not help it. I did not think about it at all; something just made me take
it."
He was convicted, of course, and I forgot the case.
But I did not forget what he had said. It remained in my mind and
recurred to me from time to time, I did not know why. For I had always
been taught that crime was due to an evil disposition which a person could
change, only he would not, and I had as yet seen no reason to question this
view. Therefore the accused's defence appealed to no idea that was
consciously in my mind. I did not reflect upon it. I can only suppose that,
unconsciously to myself, these words reached some instinct within me
which told me that they were true. And at last from the very importunity of
their return I did begin to think about them, and, consequently on them, of
the causation of crime in general. A curiosity awoke which has never
abated, has indeed but grown, as in some small ways I was able to satisfy it.

What causes crime? Is it a purely individual matter? If so, why does it
follow certain lines of increase or decrease, or maintain an average? That
looks more like general results following on general causes than the result
of individual qualities. Why is it not curable? It should have been cured
centuries ago. Why does punishment usually make the offender worse
instead of better? If his crime were within the individual's control, its
punishment certainly would deter. It does not. Any deterrent effect it may
have is rarely on him who is punished, but on the outside world, and that is
but little. So much I saw very clearly in practice, and every book I read on
the subject confirmed this. The infamous penal laws of England a hundred
years ago did not stop crime; flogging did not stop garotting, it ceased for
other causes. I began to think and to observe.
Some three years later my attention was still more strongly drawn to this
subject.
I was then for a short time the Governor of the biggest gaol in the world,
that in Rangoon. It was crowded with prisoners under sentence for many
different forms of crime, from murder or "dacoity"—that is gang robbery—
to petty theft.
The numbers were abnormal, and they were so not only here, but in all
the gaols of both the Upper and Lower Provinces. The average of crime had
greatly risen.
Why was this?
The reason was obvious. The annexation of the Upper Province six years
before had caused a wave of unrest, not only there, but in the delta districts
as well, that found its expression in many forms of crime. There was no
doubt about the cause. But this cause was a general cause, not individual.
The individual criminals there in the gaol did not declare the war. That was
the consequence of acts by the King of Burma and the Government of India
controlled by the English Cabinet, and was consequent on acts of the
French Government. Therefore half of these individuals had become
criminals because of the disagreements of three Governments, two of which
were six thousand miles away from Rangoon.

There is no getting out of that. In normal times the average of convicts
would have been only half what it was. The abnormality was not due to the
convicts themselves.
Thus if A and B and C were suffering punishment in the gaol the fault is
primarily not theirs. A special strain was set up from without which they
could not stand and they fell.
But if this is true of half the prisoners, why not of the other half? There
was no dividing line between the two classes. Political offences apart, you
could not walk into the gaol and, dividing the convicts into two parts, say:
"The crimes of this half being due to external causes, they must be
pardoned; the crimes of the other half being due to their own evil
disposition, they must continue to suffer." There was no demarcation.
Therefore, general causes are occasionally the cause of crime. Here was
a long step in advance.
Again, four years later I was on famine duty in the Upper Province, and
the same phenomenon occurred. There was an increase in certain forms of
crime. Thefts doubled. Other crimes such as cheating and fraudulent
dealings with money decreased. Here was again a general cause. Half of
those thieves would have remained honest men all their lives, been
respected by their fellow-men, and, according to religions, have gone to
heaven when they died, but for the famine.
The causes of the famine were want of rain acting on the economic
weakness of the people reared by the inability of government. Thus, had
rain fallen as usual, had the people been able to cultivate other resources,
had government been more advanced and experienced, half these thieves
would not have been in gaol; and no one knew which half, for thefts of food
did not increase. There was, in fact, no reason they should, as Government
provided on the famine camps a subsistence wage for everyone who came.
On the other hand, certain individuals were saved from misappropriating
money, or cheating in mercantile transactions, because there was little
money left to misappropriate and not much business. If they lived honestly
and went to heaven, the chief cause would be the failure of rain that year,

not any superior virtue of their own. But no one knew who these individuals
were who were so luckily saved.
But when you have acknowledged this, what is becoming of the doctrine
of individual responsibility for crime? If a man has complete free-will to sin
or not, if crime be due to innate wickedness, how does want of rain bring
this on? And where is the common sense or common justice in punishing
him for what is really due to a defective climate? He cannot control the rain.
Manifestly then, as regards at least half of these thieves, there was no innate
desire to steal, because that could not be affected by the famine. Had they
desired to be thieves they would have been so in any case. The truth is that
they did not desire to be thieves, but when the famine increased the
temptation, and, through physical weakness, decreased their power of
resistance, they fell. They sinned—not through spiritual desire of evil, but
through physical inability to resist temptation.
But if this is true of half, why not of the whole? There is no line of
demarcation. If true of some crime, why not of all? The doctrine of a man's
perfect free-will to sin or not to sin as he pleases is beginning to look shaky.
It will be as well to consider it.
What is free-will?
There is no necessity to discuss the meaning of "free"; we all know it;
there is nothing ambiguous about it; but with "will" it is different. There are
few words so incessantly misused as this word "will." Philosophers are the
worst offenders, and the general public but follow their blind lead; yet
unless you know exactly what you mean by it how can you use it as a
counter of your thought?
What does will mean? "Where there's a will there's a way"—what does
this mean? Does it mean wish? If, for instance, you are poor and stupid, can
any quantity of wish make you rich? If you are weak will it make you
strong? If you have no ear will it make you a musician? If you are a convict
can it liberate you? That is absurd.
"Will," then means more than wish; to the desire must be added the
ability—actual or potential. That is evident, is it not? Without the ability the

wish avails nothing.
"Will," then, has two complements, both of which are necessary to it. Its
meaning is not simple but compound; never forget this; never suppose that
merely wishing with all your power can produce "will." It cannot unless the
ability be developed to aid it.
And now we get back from words to human nature—Is the criminal so
because he wants to be so? No, and No, and No again. No such wicked
fallacy was ever foisted upon a credulous world as this. Nobody at any
period of the world ever wished to be criminal. Everyone instinctively hates
and fears crime; everyone is honest by nature; it is inherent in the soul. I
have never met a criminal that did not hate his crime even more than his
condemners hate it. The apparent exceptions are when a man does not
consider his act a crime; he has killed because his victim exasperated him to
it; he has robbed society because society made war on him. The offender
hates his crime.
"But he is not ashamed of it."
Now that is true. He is not ashamed of it in the current sense. He hates it;
he fears it; but it does not fill him with a sense of sin.
"Therefore," says the purist, "he has a hardened conscience. It is his
conscience, as I said, that is at fault."
But the purist is wrong. He does not understand the criminal. He has
never tried to understand him as I have tried. What the criminal feels
towards his crime is what the sick man feels towards the delirium that
seizes him—what the "possessed of devils" feels towards the possession
when it comes. It terrifies him; he knows he must succumb; he fears not the
mere penalty, but the crime. But he is not ashamed, because he knows he
cannot help it. And punishment exasperates him because he has not
deserved it, and it will do him harm, not good. He wants to be cured—not
made a fit dwelling for still worse devils. And that is what punishment does.
The effect of punishment in deterring a criminal from repeating his
crime is small. All study of criminal facts proves this. It generally makes

him more prone to crime, not less; and all the great crimes are committed
by men who have been still further ruined in gaols. What good effect
punishment may have is mainly exercised on other than the criminal.
Punishment has some effect, but how much we do not yet know, because
the matter has never been investigated, and it is not on the patient. Crime is
a disease, and will you stop a fever by punishing the patients? Whatever
good gaols do lies in the fact that they isolate the unhealthy from the
healthy and so stop for a time infection, as do hospitals with disease. But
the hospitals do not discharge the patient till he is cured; the gaol aggravates
the liability to the disease and turns out the sufferer worse than before.
Let us go back. A man is criminal not because he wishes to be so, but
because he cannot resist the temptation. He lacks will. True, but it is the
ability he lacks, not the wish. Why does he lack ability?
This brings us to the second theory of crime—a new one—that criminals
are born, not made. The tendency to crime is said to be inherent, to be a
reversion, to be inherited. That explains why it is generally incurable when
once contracted.
Many books have been written on this, but one fallacy vitiates them all.
The observers have not observed the criminal in the making but when
made. They have assumed the criminal to be of a race apart, and so founded
their house upon the sand. Lombroso went so far as to lay down certain
stigmata that inferred a criminal disposition. The stigmata have been shown
to be universal, and there is no such thing as a "criminal disposition." If
there be other qualities that do differentiate the criminal from the normal
man, they are not innate.
That those born crippled in some way frequently become criminals is no
exception; it denotes no criminal disposition. But the cripple is handicapped
in the struggle for life. He is cut off from the many pleasures of work and
play, of love and children, which his fellows have. He is sensitive and he is
jeered at and despised. Is it any wonder that under such circumstances he
becomes sometimes embittered? A cripple is set apart from his fellow-men.
There are for him but two alternatives—to be a saint or a criminal. Love

and care and training will make him a saint; neglect too often makes him a
criminal. But to whom the blame for the latter? Not to him.
Connected with this theory is the supposition that criminality is
hereditary.
There are few subjects on which so much "scientific" nonsense is talked
and written as this of heredity. Not very much is known of it as regards
plants, less of animals, and almost nothing as regards humanity.
Furthermore, the experience gained in plants and animals is useless as
regards humanity. Evolution in humanity tends to greater brain power, but
all cultivation in animals and plants has tended to destroy brain power and
even adaptability. To read books on heredity is to read a mass of
suppositions and hazardous inductions where most of the facts are negative
and the exceptions are positive. There is nothing so easy and nothing so
fatal as this tendency to attribute to heredity what is due to training, or want
of training. It excuses supineness in Governments and professions. Here is
what John Stuart Mill, a profound thinker, thought of this facile recourse to
heredity as an excuse:
"Of all vulgar methods of escape from the effects of social and moral
influences on the mind, the most vulgar is that of attributing the diversions
of conduct and character to inherent natural differences."
This, too, is what Buckle said: "We often hear of hereditary talents,
hereditary vices, and hereditary virtues; but whoever will critically examine
the evidence will find that there is no proof of their existence. The way in
which they are usually proved is in the highest degree illogical; the usual
course being for writers to collect instances of some mental peculiarity
found in a parent and his child, and then to infer that the peculiarity was
bequeathed. By this mode of reasoning we might demonstrate any
proposition. But this is not the way in which the truth is discovered; and we
ought to enquire not only how many instances there are of hereditary
talents, etc., but how many instances there are of such qualities not being
hereditary."

I have for myself, neither in life nor in books, found one single case in
which it could be confidently said that a criminal weakness was inherited.
That A, a criminal, has a son B, who also became criminal, proves nothing.
You must first prove that a similar child of different stock would not
become criminal if brought up as A's son was. You must also prove that if
you took away A's son as a child and brought him up differently he would
still show criminal weakness. But all the facts negative this. The child even
of a criminal tribe in India, if removed from its environment, grows up like
other children. Coming of criminal ancestors has not handed down a
criminal aptitude. You must not mistake inheritance of other traits for
inheritance of criminal aptitudes. A is very quick-tempered, which he has
not from a child been trained to control. Under sudden provocation he kills
a man. His son B inherits his father's quick temper, is similarly badly
brought up, and the same thing occurs. The hasty hereditary theorist says:
"Behold the inheritance of a propensity to murder." But quick temper is not
a criminal trait; it is often an accompaniment of the kindest disposition. It is
an excess of sensitiveness. The training, physical and mental, was in each
case lacking, and a coincidence of provocation caused a coincidence of
crime.
Let it be once clearly discerned that if a quality be hereditary it is always
hereditary, and cannot appear, except as the result of heredity—and the
absurdity of modern theories will be manifest.
There is not—there has never been in anyone—a tendency to crime until
either gaols or criminal education creates it. No one ever wanted to commit
crime as crime. A daring boy with no outlet for his energy may break out
into violence, robbery, and later into burglary; he would not have done so
had his physical need for exercise and his spiritual need for facing danger
had another outlet. The instincts that led him into crime were good and
noble instincts which, finding no legitimate channel, found an illegitimate
channel for themselves.
In that fine book of Mr. Holmes', entitled London's Underworld, is an
account of how hooligans are made. The young men are full of energy—
they want exercise, struggle, the fight of the football field or the hockey

match, and they cannot get it. They have no playground but the streets and
no outlet for their energy save hooliganism. The pity of it!
What, then, causes crime?
It is never the wish for crime. It is one of two causes. Either it is the only
outlet for some natural instinct which is denied legitimate outlet by the
environment, or it is due to an inability to resist temptation when it offers.
How can it be prevented?
Now this inability is physical. The wish is spiritual—the ability is
physical and depends greatly on health. With ill-health or malnutrition in
the young the first thing to give is the power of control. The average of
criminals are a stone underweight. Therefore, crime is dependent to a great
extent on health. Ill-health causes crime; accidental mutilation causes
crime; accident creates an aptitude to crime; neglected youth and education
cause crime.
Religion does not affect crime one way or another. The greatest
criminals are often religious. Mediæval Europe was very religious and very
criminal, and there are many other instances. Honesty is inborn in all; it is
part of the "light that lighteth every man that is born into this world"; it
requires no teaching. What must be acquired is the ability to give effect to
it. Crime is a physical, not a spiritual disease. And crime is no defect of the
individual. It is a disease of the nation—nay, of humanity—exhibited in
individuals. You have gout in your toe, but it is your whole system that is
wrong. This disease can be cured by Humanity alone. Criminals are those
whom we should pity, should prevent, should isolate, and, if possible, cure.
Remember what John Bradford said, looking on a man going to be
hanged: "But for the grace of God there goes John Bradford." He, too,
would have been the same had he had bad training in his youth.
We have all of us within us instincts which rightly directed result in
good, which in default of outlet we can be trained to control, but which
without outlet and without the receipt of training may result in crime. Crime
is, therefore, a defect of training and environment, not of personality.

CHAPTER XVI
COURTS REFORM
But, pending any such great change as must come in all penal law when
the subject has been carefully studied, there are many smaller amendments
that might be made both in Civil and Revenue Courts and Law.
The pressing need in Criminal Procedure is, I think, a change in the
treatment of an accused person when he is arrested.
The first instinct of an offender is, as I have said, to confess, even if an
understanding person is not available to confess to. He has offended the
Law; he wants to make all amends he can by confessing to the
representative of that offended Personality. I have seen very many first
offenders and talked to them before they got into the hands of pleaders and
others, and my experience tells me that a man who has committed his first
offence is very like a man who has caught his first attack of serious illness.
He is afraid not so much of the results as of the thing itself. Sin has caught
him, and he is afraid of sin. He wants protection and help and cure. He does
not want to hide anything; his first need is confession to some
understanding ear. Many, many such confessions have I heard in the old
days. That is the result of the first offence.
But this tendency to truth is choked when it is ascertained that as a result
the offender will be vindictively punished and made in the end far worse
than he was at the beginning. Naturally the offender says to himself: "I am
bad now. What shall I be after two years' gaol? Better fight it out. If I win
and get acquitted, at least I shall have a chance to reform. If convicted that
chance will be taken from me for ever. And fighting will not lose me
anything. The penitent prisoner who confesses gets no lighter punishment
than if he had put the Court to the expense of a long trial. Why therefore

repent? It will do me harm, not good." That is the case now; under
reasonable laws it would be the other way. But even yet in country places
he often confesses to the police by whom he is arrested.
Now by Indian Law no confession to the police may be offered in
evidence. The reason of this is that the police, in their keenness to secure a
conviction, may extort a false confession by torture, and there have been in
fact enough of such cases to cause doubt and to prevent the police being
allowed to receive a confession. Therefore if the offender wishes to confess
he is taken now to a magistrate, there his confession is recorded. Then he is
sent back to police custody. He is visited by his relatives, a pleader is
engaged for him. His folly in confessing is pointed out to him and he
withdraws the confession, alleging that he had been tortured to confess. His
confession is not only negatived, but a slur is cast on the police which is
hard to remove. Their case and evidence appear tainted, and the accused
often secures an acquittal though the Magistrate knows that the confession
was true.
All this is very common both in Burma and India, and it is disastrous to
allow and to encourage such things, as by our procedure we do encourage
them. There should be a complete change.
When a man is arrested some such procedure should be adopted as this:
He should be told by the police that he is being taken direct to the
magistrate who will try the case, who will hear anything accused has to say.
He should be warned to say nothing to the police. Then he should be taken
direct to the magistrate, who should explain to him fully what he is accused
of and ask him what he has to say.
Whatever his statement be, the magistrate should tell him that he will
himself at once investigate it and summon witnesses; meanwhile the
accused should be remitted to custody, but not to police custody. That is
where all the trouble comes in and all opportunities for making charges
against the police. If there be no gaol there should be a lock-up in charge of
Indian police who are under the magistrate and are not concerned in the
guilt or otherwise of the accused. The investigating police should only have
access to accused by permission of the magistrate. He should, however, be

allowed to see his friends and a pleader if he wish. But I am sure of this,
that the first offender would rather trust the magistrate, if he were a
personality who he knew would help him, than any pleader.
Further, if a man confess truly, his punishment should be greatly
reduced. I do not say this should be done because he gives less trouble, but
because the frame of mind induced by a free and full confession is a
sounder frame of mind on which to begin reformation than are defiance and
negation, which are now inculcated by our system.
The trial need not wait till the case is complete. The magistrate could
summon the police witnesses at once, and he should examine them himself,
allowing only the police to suggest questions if they wish. Similarly, with
the defence witnesses, they could be examined as they came in and should
be examined by the magistrate himself. No one but the magistrate should be
allowed to speak directly to any party to the case.
All cross-examination should be absolutely prohibited. If either side
have matters they wish brought out of a witness, they should tell the
magistrate and he would ask such questions as he thought fit. There is no
such curse now to justice as cross-examination by a clever pleader or
barrister. It is a sort of forensic show-off by the advocate at the cost of the
witness, and frequently at the cost of justice. For, naturally, no one cares to
be bullied by a licensed bully, and witnesses consequently will not come to
Court if they can help it. When in Court they are bamboozled and made to
contradict themselves where they have originally spoken the truth.
I have often been told that acute cross-examination by a clever barrister
is the greatest safeguard justice can have from false evidence. I don't
believe a word of it. A magistrate can by far fewer and simpler questions
expose false evidence better than an advocate does, because the magistrate
is intent only on his business—to find the truth; the advocate is advertising
himself, and trying to destroy truth as well as falsehood.
But if the magistrate did all the questioning I don't believe there would
be much false evidence. Witnesses will lie to the opposite side, but not to an
understanding Court.

Perjury would disappear. What is its present cause? Contempt of the
Court and sympathy with either complainant or accused, which sympathy
sees no chance of justice for its object except by perjury. Because a trial is a
fight. There is not a human being East or West who would not be ashamed
to lie to a Court he knew was trying to do its best for all—parties and
public. It is because the Courts as at present constituted do as much harm as
good that perjury is rampant and condoned. It is so in all countries, it has
been so in all periods.
Then, as soon as possible, juries should be introduced. This cannot be
done until the law, especially as regards punishment, is greatly altered in
accordance with the common sense of the people, but it is the objective to
be aimed at as soon as possible. Until the public co-operate with the Courts
in all ways you will never have a good system of justice. Crime hurts the
people far more than it hurts Government. Don't you think the people know
that? And don't you suppose they want it prevented even more than
Government does? In any case that is the fact. They hate the Courts now
because they don't prevent or cure crime; they only make matters worse.
The only objection I see to this proposed alteration is that it will take
more time and so cost more money. At first it may do so, but even then
what the public loses by more taxes it will more than save in having to pay
less to lawyers. How much unnecessary money is now paid to lawyers?
Enough, I am sure, to double the magistracy and then leave a big balance.
Courts should be made for the people, not for lawyers. And in time crime
would so decrease that there would be saving all round.
The reform of the Civil Courts should follow somewhat the same lines.
A man should not have to wait to see a civil judge till his case is all made
out. He should be able to go to him at once and confide in him, and the
judge should send for the other party and try to make an arrangement
between them so that no suit should be filed. Not until that has been done
and not unless a judge give a certificate of its necessity should a suit be
allowed to be filed as it is now. And then when it is filed the judge should
conduct the case and not the advocates on each side. That is the only way to

stop the perjury which increases and will increase. Magistrates and judges
must cease to be umpires of a combat, and become investigators of truth.
As regards the laws of marriage and inheritance, no great change can be
made until there is a real representative Assembly to make these changes,
but even there something could be done. That fossilisation of custom
described by Sir Henry Sumner Maine should stop. Because a High Court
proved a hundred years ago that a certain custom existed there is no
evidence that it does or should exist now. To establish precedents of this
nature is to stop all progress of every kind; we have a vision different from
the poet's
Of bondage slowly narrowing down
From precedent to precedent.
Why should not fresh inquiries into custom be made from time to time, it
being understood that any Court-ruling only applied to that time and place,
and did not bind the future? Something must be done. Things cannot go on
as they are. We reproach the Indians for want of progress, but we ourselves
are the main cause of that stagnation. We bind them and they cannot move.
As regards land policy there is this to be said, that fixed ideas are a
mistake.
In Bengal there was at one time a fixed idea that all land did and must
belong to large land-owners, and so, partly out of sheer ignorance, partly
out of prejudice, a race of Zemindars was created out of the tax-gatherers to
the Mogul Empire. The result has been sad.
Again in Burma the same idea prevailed for a while, and headmen were
encouraged to annex communal waste as their private land. This was
unfortunate.
Then came a reaction, and all large estates were denounced as bad. There
was to be a small tenantry holding direct from Government, forbidden to
alienate their land, and all leasing of land to tenants was forbidden.

This I understand to be the policy still. It is a policy of fixed ideas, and
as applied to anything that has life, like land tenure, it is unfortunate, no
matter what the fixed idea be.
If there be one truth above another that is clear in studying land systems
it is that no one permanent system is good. The cultivation of land, like all
matters, undergoes evolution and change. What is good to-day may not be
good to-morrow. The English system of large estates cultivated by tenants
did, at one time in English history, produce the best farming in the world.
English farming was held up as an example to all countries and was so
admitted by them. The system of large estates allowed of the expenditure of
capital, experiments in new cultivations and new breeds of cattle, and
variety of crops. It suited its day well. And though its full day has passed,
there will never be a time when some large estates will not be able to justify
themselves. Even if, as apparently is the case now in England, petite culture
is that best adapted to the cultivation of the day and the needs of the people,
yet there is still room for large estates. A dead uniformity of small holdings
could not but be unfortunate for any country.
Further, although excessive alienation of land through money-lenders
may be very bad, yet stagnation in ownership may be worse. India and
Burma are progressive, and changes must take place. Cultivators will
become artisans and traders; city people will like to return to the land. There
is an ebb and flow which is good for all. Too great rigidity of system will
stop progress. A good system of land tenure is that which is in accordance
with the evolution of the people it applies to and assists in that evolution.
While recognising that for the bulk of the people small holdings are best,
it will not forbid larger estates; while admitting that the alienation of land
through borrowing recklessly from money-lenders is bad, it will see that the
progress of the people from purely agricultural towards a state of industrial
activity is not checked. It takes all sorts to make a State.
It may be good for the cultivator to hold direct from Government, but if
Government is to be the landlord it must act up to its name. It must give
compensation for improvements when a tenant has to relinquish the land.
Otherwise no tenant will improve, and the necessity for improvement, for
wells, irrigation, embankments, manuring, and so on, is the greatest

necessity of agriculture. In my own experience I have seen that the system
of State land tenure in Upper Burma does stop improvements.
That is the light in which the land question has to be worked out, on
broad comprehensive lines—that, while acknowledging the present, sees
also the future, which, while seeing one form of good does not deny
another.
So, with an understanding and a sympathetic personnel, the
administration would be brought nearer to the people, until at length when
their capacity for self-government had developed they would be able to take
over our administrative machine little by little and work it themselves.
They could never do that now. If by any chance they did get possession
of the machinery at present, they would set to work to smash it till none
remained.
CHAPTER XVII
SELF-GOVERNMENT
And thus the sheltering Government of India having been reformed both
in its personnel and in its laws, brought into touch and sympathy with its
people, a start would be made with self-government.
That, of course, must begin with the village, which is the germ from
which all self-government that is of any value has always begun, and on the
health and vitality of which it must always depend. The village organism
must be restored to the state in which we found it, and from that be helped
and encouraged to grow to greater things.
The whole of the present conception of the village as an appanage of the
headman, and the conception of the headman as an official of Government,

must be swept away and a new and true conception must be arrived at.
The village is a self-contained organism, and the headman is its
representative before Government and its executive head, the real power
being in the Council. Powers and responsibility reside in the village as a
whole and in no individual. The people must not be ruled, but rule
themselves.
Now as to the exact way in which this conception should be carried out
it is impossible to say. In each Province—in distinct parts of the same
Province—the village system assumed different forms to meet different
circumstances. In Madras the village community was in many details
different from that in Burma, and in the North-West still more so.
Therefore, the particular way in which the conception should be realised
would vary greatly. And only by experience could a satisfactory form for
each Province be evolved. Neither would it be possible even in Burma to go
back to the old form exactly. Events have marched since then, and what was
satisfactory thirty or more years ago would not be so now. The villages
must not be reconstituted by copying the past; they must be constituted
anew, maintaining, however, the spirit of the past and giving scope for
evolution in the future.
Therefore, the scheme that I am about to unfold must be taken to be
merely tentative and apply only to Burma. The principles are, I think, right;
the details must, of course, be discovered by experience. Practice alone
would show how far they realised the objective that is to be aimed at—the
constitution of a village organism on natural lines that would govern itself
without any need for interference and would be able to grow and evolve.
My scheme is as follows:
In every village a Council should be constituted and the headman should
be its executive head.
How this Council should be constituted I do not know. I think there
should be wards, each of which should have an elder, representative of the
people, but no rigid system of election should be laid down. I have found
that villages and wards can very often appoint a representative man by

general consent, which is much better than by election. That should only
occur in case of a dead-lock. The Council should itself define the wards,
and it should be allowed to co-opt additional members. All representation
by class or religion should be prohibited. The unit is not so many people,
but a section of a village—neighbours dwelling together and whose
interests are thereby united. Appointment to the Council should be
indefinite; that is to say, an elder should remain an elder until he resigned or
until the ward turned him out. I don't think they would like continual
elections. An election is a bad means to a desired end—that of obtaining the
best representative. And in small communities the sense is usually apparent
without it.
The headman should be chosen by the Council from among its members
and his election confirmed by Government. His appointment should be
according to the wish of the Council, that is to say, for life, unless he
resigned or the Council turned him out. He should be responsible to the
Council. The Council, as representing the village, should be responsible to
Government, and it would always be possible for the Deputy Commissioner
to bring pressure on a recalcitrant Council by threatening to suspend the
constitution and place the village under an appointed headman for a time if
they did not carry out their duties properly.
To this village community should be handed over certain duties, rights,
and responsibilities, much what the headman has now, the collection of
revenue, etc. All civil, criminal, and revenue cases under certain values and
of certain denominations should be handed over to them to try; that is to
say, that cognisance should be refused by our police and our Courts, so that
the parties could go to the Village Council if they liked. There should be no
appeal from the decisions of the Council, no advocates should be allowed,
and no record should be required. All penalties imposed should be paid into
the village fund.
This fund should exist for all villages, and its nucleus should be, say,
half an anna in the rupee of the revenue collections, to which should be
added fines, special rates which the Council should be empowered to
impose for specific purposes, and other forms of revenue which would vary
from place to place. I think a percentage of the district fund should be given

to them. A rate on inhabited houses—a rent on house sites—would be a
good way of raising money. The purposes for which the fund could be used
would be water-supply, sanitation, roads, lighting, watchmen, and so on.
Simple account-books would have to be kept, and these accounts would
have to be audited once a year.
Model schemes for sanitation, village roads, etc., could be made out for
each village to live up to as fast as it could.
Further, villages should have the power to carry out irrigation works on
their own initiative and under their own control. I consider this a most
important proviso, because I know many villages where this could be done
by the village, whereas it is not possible to individuals. I also know one
recent case in my district where it was done with great success by the
headman and elders. I got them a small grant, and I often went to see how
the work was getting on, but I never interfered in any way, and the result
was most satisfactory. There was at first a difficulty about collecting the
rates, because there was no legal system under which a man who used the
water could be made to pay. However, this also settled itself.
Irrigation works, roads, and bridges are most necessary to many villages,
but now, unless Government carry out the work, there is no one to do it.
And Government will not carry out small works.
It is by the execution of such works that the village would prosper and
the village fund grow. Loans should be granted for these purposes by
Government, to be repaid out of the profits.
Before our annexation all works were executed by the villages, and the
considerable irrigation works in many places are evidence of their ability.
All this initiative has now been killed. Yet it is a most valuable asset, not
only materially, but morally.
As regards this fund, it will, I know, be objected by many people that it
will be simply an excuse for peculation. "Orientals," they say, "cannot be
honest, and the funds would be misappropriated right and left."

Exactly this same charge was made when the Co-operative Credit Banks
were started. Their history will sufficiently refute such an absurdity.
Orientals are just as honest as any other people, and, given a good system,
village funds will no more be stolen in India or Burma than municipal funds
are in England.
In organising these villages there is another point to be borne in mind. In
that desperate struggle after rigid uniformity which distinguishes the Indian
Government, every separate hamlet in Burma was put under a separate
headman, and thus made a separate organism.
Now it may be that occasionally the village was too large, and a division
was needed, but in many other cases the disintegration of long-established
units was severely felt. Several hamlets may have one interest in common.
They may be grouped round a small irrigation work, or along a stream, or
have a fishery in common, or be in other matters of great use to each other.
If run as separate organisms there is bound to be strife, each trying for his
own benefit. If allowed to remain one organism they will be not only more
peaceful, but stronger, and better able to manage their affairs. Thus the rigid
formulæ of Government in this matter as in others should give place to
common sense.
Further: in future, villages should be allowed to coalesce if mutual
interests attract them. Two or three villages if allowed to combine would
carry out works that one could not do.
I see no great difficulty in Burma in thus restoring the organism of
village life. It would require mainly tact on the part of the District Officer
and ability to let alone. His tendency now is always to interfere if he can.
His rule should be never to interfere if he can help it. When things go wrong
persistently it will probably be found that there is something amiss with the
way the village is organised, and that it requires some slight modification. If
a horse can't draw a cart it is better to see what is wrong with the horse or
the cart than try to move them both along by turning the wheels round
yourself. You won't get far that way. The more you push the more the horse
will jib. And Village Councils will be very willing horses if let alone and
the cart be not too cumbersome or the hill they have to climb too steep. But

they must be left alone. Read the history of municipal institutions in
England and note the principles. They are universal.
Once the village communities are strong and healthy, a further step could
be made by instituting a township or sub-divisional Council, and later a
District Council.
For these I am not prepared to offer any suggestions. It would require a
very careful study of local conditions and of the people, a wide experience
gained from the working of the resuscitated villages, to know how these
should be constituted and what powers and responsibilities should be
entrusted to them. I think a sound analogy might be obtained from a study
of English counties—not so much perhaps as they are now, but as they were
—in spirit, not in law.
After the village organism was established, perhaps in order to its proper
establishment, a local Government Board would have to be created. This
would have to be in time entirely native to the Province. It is, I think,
essential that it should be so. What its relations with the District Officer
would be I do not know. I foresee difficulties. It is essential for good order
in the district that there be no one between the head and the people.
Nevertheless, I don't think he could establish and work the village organism
himself. I think he would be too tempted to interfere; and, moreover, there
would have to be a certain co-ordination between the systems in various
districts. They need not be the same in detail, but the idea should be the
same. That is because eventually they must coalesce into bigger organisms.
But a District Officer with a strong personality would, I think, be liable to
impress that personality on the village, and as it must be self-governing that
might create difficulties. For as the villages increased the District Officer
would decrease. Gradually his powers would devolve on the local
organisms. There would thus be a certain rivalry between the District
Officer and the local organisms, which, if the officer were the head of both,
might result in injury to the latter. Perhaps some such relation as exists
between the Land Records Department and the District Officer would be
possible. The Land Records has its own organisation, which works
independently of the district but in harmony with it. All this, however, is not
a matter which can be thought out. It will have to be worked out, and a

correct system can only come little by little, experience showing how
modifications should be made. I do not see any great difficulty provided
there are common sense and unity of aim on both sides.
And from districts—when they had settled down into distinct organisms
more or less self-governing—representatives, not delegates, could be sent to
a Provincial Council. Then you would have a real Council, one
representative of the people because proceeding from the people, not less
surely because not directly. I am not sure that direct election such as is
practised in England and America, for instance, does cause representation
of the people. In England, at all events, it is not so now. The only power the
people have now is to choose between the delegates of two or more parties.
Beyond this they have no voice nor choice. They cannot find any
expression for their own wishes. Their member may be, probably is, a man
they never heard of before the "Party" sent him to contest the seat. There is,
in fact, in England to-day no real representation of the people at all. By
people, of course, I mean the people as a whole, including all classes. But
under some such scheme as I have sketched out for Burma there would be
real representation of the people, of localities as a whole, units; local men
acquainted with the local conditions would be chosen and not pleaders, and
the locality would hold them responsible. Thus the opinion of such a
Council would represent the wishes of the people; it could be depended on,
and to it could considerable powers be delegated permanently. It would, in
fact, in time constitute a Provincial Government in federal relations with the
other Provincial Governments. That is the only possible way that a real
government can be built up.
And it must always be remembered that the basis is the Village. On the
health of the Village all other things depend; from the healthy working of
the Village all things may proceed. It is the first but not last word in local
self-government.
A very integral part of any self-government is Education, and to that I
come in the next chapter.

CHAPTER XVIII
EDUCATION
To the success of any form of self-government a good education is
absolutely essential; that a people should be able to exercise self-
government it is necessary that they be educated to self-government; for
this capacity no more comes by itself than ability to build a ship or steer it
when built. And as the government must be self-government, so the
education must be a national education and not an imported one.
I have already had something to say on this subject in former chapters
when writing of the Indian civilian, and the principles which underlie good
education are the same everywhere. A well-educated man is he in whom his
mental and physical powers have been so brought out that he can face the
ordinary vicissitudes of his life with confidence, that he can understand
them and combat them materially to the best of his ability, and that when
materially defeated he may still rise spiritually above all defeat and
discouragement. Education is necessary to everyone—man or woman,
peasant or prince, merchant or artisan—and that man is best educated who
can make the best of his life whatever its station may be.
Thus it will be seen that education is mainly relative. A man who would
be well educated if in one station of life would be hopelessly ignorant if in
another. I doubt if Whewell would have been considered educated had fate
suddenly made him a soldier, a political officer on a frontier, or a cultivator.
A keen eye gained by experience for market fluctuations is better for a
merchant than all the learning of all the libraries.
But this specialisation belongs properly to higher education. There are
certain foundation principles necessary to any success in life, to being able
to live it in whatever station with dignity and with prosperity. What are
those principles?
I think the Indian Education Department would say that these are
reading, writing, and arithmetic—that is to say, acquirements. I should say

they are qualities of character.
What are these qualities?
First and foremost is belief in his own people, not his caste or his creed,
but in the people who inhabit his Province, who will eventually make up his
nationality. If the man is to do good work for his people the boy must desire
to do good work—he must have a certainty in the unlimited possibilities of
his people, that though they may be young now they will grow to a world
stature. Therefore, that it is his duty to help them. He must be sure that this
world is good—to be made better by him and his fellows and his
descendants. He has inherited much; he must hand on more. He has no right
to live unless he does his duty to life and in life—that is to say, he must
have a purpose in life, for without a purpose life cannot be lived.
Secondly, he must see that to the accomplishment of his purpose, which
is but part of the World's Purpose, he must cultivate two qualities,
obedience in act and freedom of thought. He must learn to obey, because he
must see for himself that only by men acting together under authority can
anything be achieved. His obedience will then be a willing and cheerful
obedience, because necessary to his own purpose. He must obey that later
he may be obeyed. He must keep his mind free, because to admit authority
in thought is to kill thought. He must see things for himself and judge for
himself, that when he is able to act for himself he may do so on truth and
not on hearsay. He must learn to respect the opinions of others which they
have founded also on experience, while not necessarily adopting them,
because he may see things differently.
He must learn self-knowledge to recognise what he can do and what he
can't.
He should cultivate self-command that must not mean self-extinction.
On a base like this all other things come naturally.
Is there any such ideal in elementary education in India? I can safely say
that there is no such ideal. All that the Department seeks to do is to stuff a

child with reading, writing, and arithmetic, and other learning, regardless of
his character or his objective in life.
Therefore elementary education is not popular in Burma, because it
seems to have no good purpose.
That was true of education before we took the country. It was then
mainly, for boys, in the hands of monks, and I do not think that education
when controlled by religion has been popular anywhere in the world. It has
been accepted because there was no other means of education available, but
it was not admired. Our Government has accepted the monastery schools,
and it has also encouraged lay schools, but neither seem to give much
satisfaction.
Now this is not the place to discuss religion of any kind, and I have no
intention of entering into such a vexed question. There are good things in all
religions—borrowed from humanity; there are doubtful things; there are
bad things. But the foundation of every religion is a declaration that this
world is evil and that we should despise it. Now the objective of all
education is to fit a boy for his life, and he cannot be so fit if he despise life.
He must love it, admire it, desire in all ways to help it, to increase it,
beautify it. His objective must be in this life. Further, the tendency of all
faiths is to raise barriers between races and castes. But it is an essential part
of any true education that a boy understand that in striving for the good of
the community he must ignore all differences. Humanity is one, and the
God of Humanity is One, whatever faiths may say.
Thus religions when mixed with education have a paralysing effect. I
have often heard this said in Burma. Here is a conversation I once had at a
village I knew very well. It occurred, as did most of the talks I had with the
people, just after sunset, when I had my chair set outside my rest-house, and
the people came dropping in to gossip. There were a number of people, the
headman, elders, their wives and children, and two monks from a
neighbouring monastery. They talked quite freely because they knew that
after office hours I forgot I was an official, or even an Englishman, and just
talked to them as one human being to another. I may add that I had been
inspecting the village school where little boys and girls learned together. I
had also been to a monastery where the elder boys went.

"Well," I said, "what is the news?"
There was an expectant silence. Evidently there was some news; the
question was—who should tell it?
"What is it, Headman?" I asked.
The Headman rubbed an ankle reflectively. "The fact is," he answered,
"there is no news that would interest your Honour; only just village doings,
foolish doings."
"Hum," I said; "that sounds to me as if a young man had been doing
something."
Several of the men smiled—"Possibly with the assistance of a girl"—and
I glanced at some girls. They giggled, and the Headman said briefly:
"Maung Ka's son has run off with a girl."
"Oh!" I said, turning to Maung Ka, whom I knew well enough—a tall,
fine-looking man, who was looking very gloomy. "It's a way boys have.
There's no harm in it."
"Not if he can support her afterwards," said Maung Ka gruffly.
"Can't he do that?" I asked.
It appeared he couldn't. He had spent all his boyhood in a monastery
"learning" till his father fetched him out. Then he went to the other extreme
and levanted with a girl. "He doesn't know one end of a bullock from the
other," said the father; "he can't plough or sow; he can't work; he has no
common sense. That's what schooling does for a boy."
Most of the other men agreed with him, and we had a discussion on
education, in which everyone took part.
The general opinion was that schooling should be to fit you for life. The
monks said for eternity, but the villagers—though out of respect for the
monks they said little—evidently didn't make any such distinction. What

wasn't fit for time wasn't fit for eternity. Reading, writing, and arithmetic
were good, because a boy needed these. Beyond that they seemed to think
schooling did harm. A boy learned more from his father and the other
villagers than from school. As to a girl, "What," asked an elder indignantly,
"is the use of a girl learning to write? What will she write? Love-letters
only."
"Well," I asked, "and isn't that good—for the boy who gets them?"
The fact is, the villagers are plain, common-sense men and women, and
what they want for their children is that they be better fitted for the struggle
of life. They do not observe that to be the case at present. They judge by
results, and the results are not good, they say.
In fact, except as to the actual acquisition of reading, writing, and
arithmetic, which may or may not be of much use, the teaching—and still
more than the teaching, the influence—is bad. It unfits for life, it gives
wrong ideals, or it kills all ideals.
The higher education is, I think, worse. It follows an imported system,
and in the importation all the good is left out. In England a boy's real
education comes from association with the other boys and from his father.
From them he learns whatever he does learn of conduct, of ambition to true
ends, of acting in concert, of ability to judge for himself and stick up for
himself.
In India a wrong ideal has been conceived from the beginning. It has
been assumed, tacitly maybe, that an Englishman is the final and
completely perfected work of God and man, and that all nations should
copy him and try to become, if not a sterling Englishman, at least an
electro-plate one.
That is disastrous. It depresses the people by depreciating their own
races and holding up an objective which is impossible, and if possible
would be wrong.
There are in the pasts of nearly all Oriental people ideals which are quite
as good as ours, and far better fitted for them. Are these ever taught to

them? India once led the civilisation of the world; is that past ever brought
up and explained and realised for them? Never, I think.
Further, higher education to be of any use must be objective. You must
know what you want the boy to be. What does Government want the
products of its higher education to be? I have no idea. Has the Government?
Of what use are these products of the higher education in India? They
are useful but for two things, to be lawyers or pleaders, or to be clerks. They
are dealers in words, and not in facts or in humanity.
Government accepts a certain number into its service, because the first
ideal of Government is a man who can fill up forms and returns, speedily,
accurately, and punctually. They can do that. When they have district work
to do they fail, because they have no personality, no freedom of thought,
and because the people despise them. The old officials whom we took over
from the Burmese Government, whatever their defects, had "auza"—
personality. It is a commonplace to say that the Burmese have deteriorated.
That is not true. They have as much potentiality as before, but this
potentiality is wiped out by "education." Far from being really educated,
they are merely stuffed, and their natural abilities stifled. Moreover, they
cease to be Burmans, or Madrassis, or Bengalis, and become a sort of
hybrid. This is due to their English masters, who are obsessed with the idea
that the only way to "educate" anyone is to turn him into a plaster
Englishman. I have had some experience of these unfortunate boys who
have taken degrees.
Personally, if I had to administer a difficult district, I should choose my
Burmese assistants from men who had never been to school, and to satisfy
Government I would engage some B.A.'s and F.A.'s to be their clerks and
fill up the forms. I should be sorry for the B.A.'s, because I think they have
as good stuff in them as the others, but their want of education has unfitted
them for work requiring "auza."
That is really what it amounts to; the school-trained boy is not educated,
whereas the boy brought up in contact with the world is perforce educated.
The first is a hothouse plant; the second a useful field plant.

I am aware that current opinion puts down the failure of the educated
young Indian to his want of religion. He has been educated out of his own
faith and not accepted into any other; hence his want of character. Of all the
wild shibboleths about India and the Indians this is, I think, the wildest.
That a man is injured by being brought to see the foolishness of caste, of
infant marriage, of harems and zenanas, of all the forms and ceremonies
with which all religions are covered, seems to me a triumph of illogic. Only
the "Occidental mind" at its best could conceive such an idea. In so far as
education destroys these ideas it does good. Wherein it harms him is by
taking him apart from his people, rendering him not desirous to help them
but to disown them. He is taught that to be an Englishman should be his
ideal—that he "should cultivate English habits of thought"—as if true
thought had any habits—so that, finally, he can't think at all. He is directed
to wrong ideals; he is rendered unhappy; he is dépaysé; he is useless for any
work, except being a clerk or lawyer; he has no more character than a jelly-
fish. Instead of wishing to lead his people he wishes to identify himself with
the English Government, be a civilian, and rule his people. He should be
filled with a boundless confidence in the future of his people, and that it is
his duty to help that future to be realised. He is discouraged and rendered
hopeless. Instead of being a help he is the greatest danger his own people
will have to meet when they move forward. He is a danger to all.
The Education Department of the Government of India is the new
Frankenstein, and the Higher Education is its monster. The students have
sunk under their "education," and in consequence they are unhappy. Who
wonders? But, in fact, an alien Power cannot introduce or work any real
system of education. It must be indigenous—something of the soil, and not
exotic. It, like self-government, must begin with small things in the village
and gradually rise.
Like all things, if it is to live and prosper and extend it must have a soul.
And the soul of education, like the soul of life, is an emotion tending
towards a desired end. The desired end of education is the rise and progress
not merely of the individual but of the nation. That has been the soul of the
progress of Japan; that must be the soul of the progress of any people; and
education will only be enthusiastically taken up when it is seen to be a
means to that end.

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