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Reference on using bio-nanomaterials to remove pollution in industrial sectors ranging from food and agriculture to oil and gas

Bio-Nanomaterials in Environmental Remediation discusses the application of bio-nanomaterials in various industrial settings.

Bio-Nanomaterials in Environmental Remediation includes information on:

  • Fundamentals, classification, and applications of bio-nanomaterials, technologies for the fabrication of bio-nanomaterials, and desalination of wastewater using bio-nanomaterials
  • Applications of bio-nanomaterials in the textiles, oil, gas, food, and agriculture industries
  • Hazard, toxicity, and monitoring standards of bio-nanomaterials
  • Current challenges of bio-nanomaterials in industrial applications and future outlooks in the field
  • Strategies to manage the safety of bio-nanomaterials to enable the creation of healthy and pollution-free environments

Bio-Nanomaterials in Environmental Remediation is an essential up-to-date reference for professionals, researchers, and scientists working in fields where bio-nanomaterials are used.

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Table of Contents

Cover

Table of Contents

Title Page

Copyright

Brief Biography of Editors

Preface

1 Bio-nanomaterials: An Introduction

1.1 Introduction

1.2 Types of Bio-nanomaterials

1.3 Integration of Nanoparticles and Biomolecules

1.4 Application of Bio-nanomaterials

1.5 Advantages of Bio-nanomaterials

1.6 Current Challenges and Future Prospects

1.7 Future Perspectives

1.8 Conclusion

References

Note

2 Classification and Applications of Bio-nanomaterials

2.1 Introduction

2.2 Etymology of Nanotechnology

2.3 Why Bio-nanomaterials Are Required?

2.4 Categories of Bio-nanomaterials

2.5 Classification of Bio-nanomaterials

2.6 Application of Bio-nanomaterials

2.7 Toxicity of NPs and Nanomaterials

2.8 Conclusion

References

3 Technologies for the Fabrication of Bio-nanomaterials

3.1 Introduction

3.2 Bio-nanomaterial Types

3.3 Technologies for the Fabrication of Bio-nanomaterials

3.4 Microorganisms as Instruments for Nanofabrication

3.5 Synthesis Mediated by Plants

3.6 Production of Bio-nanomaterials via Enzymatic Process

3.7 Cellular Nanotechnology

3.8 Peptide Self-assembly

3.9 Liposome Technology

3.10 Bio-nanomaterial Applications

3.11 Issues and Prospects for the Future

3.12 Conclusion

References

4 Desalination of Wastewater Using Bio-nanomaterials

4.1 Introduction

4.2 Desalination Tactics

4.3 Cursory Analysis of Traditional Desalination Techniques

4.4 Limitations of Traditional Desalination Methods

4.5 Emergence of Bio-nanomaterials

4.6 Miscellaneous Use of Nano-biomaterials

4.7 Properties of Bio-nanomaterials and Their Role in Desalination

4.8 Bio-nanomaterials for Wastewater Desalination

4.9 CNT Membranes for the Removal of Salt

4.10 Carbon Nanotube-Based Purification

4.11 Mechanisms and Influence Factors for Desalination

4.12 The Properties of Carbon Nanotubes Impacting Water Flow Rate

4.13 Environmental Impact and Sustainability

4.14 Future Aspects

4.15 Conclusion

References

5 Industrial Applications of Bio-nanomaterials in Textiles

5.1 Introduction

5.2 General Processes in the Textile Industry

5.3 Conventional Textile Fibers

5.4 Biomaterials for the Textile Industry

5.5 Conclusion

References

Note

6 Industrial Application of Bio-nanomaterials in Oil Industry

6.1 Introduction

6.2 Characterization of Bio-nanomaterials

6.3 Nanomaterials for Oil and Petrochemical Industries

6.4 Separation Techniques

6.5 Nanomaterials for the Oil and Gas Industry

6.6 Upstream Process

6.7 Role of Bio-nanomaterials in Oil Recovery

6.8 Catalytic Properties

6.9 Conclusions and Future Prospectus

References

7 Applications of Nanotechnology and Nanomaterials in Gas Industry

7.1 Introduction

7.2 Why Nanotechnology in Gas Industries?

7.3 Applications of Different Nanomaterials

7.4 Different Types of Nanomaterials Used in Gas Industries

7.5 Challenges of Nanomaterials Used in Gas Industries

7.6 Future Prospects of Nanotechnology and Nanomaterials in Gas Industries

7.7 Conclusion

References

8 Industrial Application of Bio-nanomaterial in Food Industry

8.1 Introduction

8.2 Nanomaterials in Food Packaging

8.3 Carbon Nanomaterials

8.4 Silicon Nanomaterials

8.5 Metallic Nanomaterials

8.6 Nanocomposites

8.7 Bio-nanocomposites

8.8 Natural Polymers

8.9 Biodegradable Synthetic Polymers

8.10 Mechanisms of Antibacterial Action

8.11 Nanobiosensor in the Food Industry

8.12 Incorporation Techniques

8.13 Nanotechnology in Food industry

8.14 Environmental and Safety Issues with Food Packaging Using Bio-nanotechnology

8.15 Conclusion and Future Perspectives

References

9 Industrial Application of Bio-nanomaterials in Agriculture

9.1 Introduction

9.2 Fundamentals of Bio-nanomaterials

9.3 Source of Bio-nanomaterials

9.4 Difference Between Nanomaterials and Bio-nanomaterials

9.5 Utilization of Bio-nanomaterials in Agriculture

9.6 Future of Industrial Bio-nanomaterials

9.7 Toxic Effects of Bio-nanomaterials in Agriculture

9.8 Challenges and Opportunities in Commercializing Bio-nanomaterials in Agriculture

9.9 Case Studies

9.10 Guidelines and Regulation for Evaluation of Nano-Agri input Products and Nano-Agriproducts

9.11 Conclusion

References

10 Bio-nanomaterials: Hazard, Toxicity, and Monitoring Standards

10.1 Introduction

10.2 Hazards Associated with Bio-nanomaterials

10.3 Toxicity of Bio-nanomaterials

10.4 Factors Affecting the Toxicity

10.5 Toxicological Evaluation of Bio-nanomaterials

10.6 Regulatory Aspect

10.7 Conclusion

References

11 Challenges and Fate of Bio-nanomaterials in Industrial Applications

11.1 Introduction

11.2 Challenges of Bio-nanomaterials in Wastewater Management

11.3 Challenges of Bio-nanomaterials in Textile Industries

11.4 Challenges of Bio-nanomaterials in Oil Industries

11.5 Challenges of Bio-nanomaterials in Gas Industries

11.6 Challenges of Bio-nanomaterials in Food Industries

11.7 Challenges of Bio-nanomaterials in Agriculture

References

12 Future Aspects in the Field of Bio-nanomaterials Toward Environmental Assessment

12.1 Introduction

12.2 Evolution of Bio-nanomaterials

12.3 Current State of Bio-nanomaterials in Environmental Assessment

12.4 Future Prospects and Innovations

12.5 Regulatory Frameworks and Safety Guidelines

12.6 Interdisciplinary Collaboration and Research Directions

12.7 Conclusion

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Overview of various strategies for biomolecule–nanoparticle integr...

Table 1.2 Various conjugation strategies and applications for nanoparticles ...

Chapter 2

Table 2.1 Overview of organic nanoparticles.

Chapter 4

Table 4.1 Methods for characterizing carbon nanotubes.

Chapter 6

Table 6.1 Properties of bio-nanomaterials.

Table 6.2 Process and benefits of nanomaterials in diverse processes of the ...

Table 6.3 Nanoparticles in the Oil and Gas Industry and their Applications....

Chapter 8

Table 8.1 Application of starch-based nanocomposites in the food industry.

Table 8.2 Utilization of chitosan-based nanocomposites in the food sector.

Table 8.3 Utilization of cellulose-based nanocomposites in the food industry...

Table 8.4 Application of protein-based nanocomposites in the food industry....

Table 8.5 Antibacterial mechanism of nanomaterials.

Table 8.6 Nanosensors utilized for the pathogens detection.

Chapter 9

Table 9.1 Potential risks associated with bio-nanomaterials in agriculture....

Table 9.2 Challenges and opportunities in commercializing bio-nanomaterials ...

List of Illustrations

Chapter 1

Figure 1.1 Applications of bio-nanomaterials. The figure illustrates the div...

Figure 1.2 Classification of bio-nanomaterials. The figure presents a classi...

Figure 1.3 Bio-nanomaterials in the food industry. The figure showcases the ...

Figure 1.4 Versatility of bio-nanomaterials in environmental applications. T...

Chapter 2

Figure 2.1 Classification of nanomaterials based on dimensionalities. This f...

Figure 2.2 Types of organic nanoparticles. This figure delineates various ty...

Figure 2.3 Susceptibility of organic nanoparticles to thermal and electromag...

Figure 2.4 Carbon-based nanoparticles. This figure illustrates a category of...

Figure 2.5 Metal nanoparticles in inorganic bio-nanoparticles. This figure i...

Figure 2.6 Desirable characteristics of polymer therapeutics. This figure de...

Chapter 3

Figure 3.1 Mechanistic biofabrication of nanoparticles using nanofactories....

Chapter 4

Figure 4.1 Employment of various types of nanomaterials for desalination of ...

Figure 4.2 Employment of various methods for desalination of saline water. (...

Figure 4.3 Various roles of nanomaterials.

Figure 4.4 An illustration of the range of applications for the studied memb...

Figure 4.5 (a) Water molecule mass transfer in a GOM is shown./with perm...

Figure 4.6 Membranes made of carbon nanotubes (CNTs) in different configurat...

Figure 4.7 Desalination with functionalized carbon nanotubes (CNTs).

Chapter 5

Figure 5.1 Molecular structure of chitosan.

Figure 5.2 Structure of cellulose.

Figure 5.3 Structures of chitin and chitosan.

Chapter 6

Figure 6.1 Overview of nanoparticle synthesis methods in the oil and petrole...

Figure 6.2 Integrated processes in the oil and petroleum industry.

Figure 6.3 Applications of nanoparticles in oil and petroleum industry.

Chapter 7

Figure 7.1 Applications of nanotechnology and nanomaterials in gas industrie...

Figure 7.2 Types of nanomaterials used in gas industries.

Figure 7.3 Classification of nanomaterials used in gas industries.

Figure 7.4 Challenges of nanomaterials.

Chapter 8

Figure 8.1 Nanotechnology for food packaging and security.

Figure 8.2 Mechanisms of antibacterial action.

Chapter 9

Figure 9.1 Properties of nanomaterial and their importance of nanotechnology...

Figure 9.2 Future of industrial nano-biomaterials with reference to bioethic...

Chapter 10

Figure 10.1 Factors affecting the toxicity and cellular damage.

Chapter 11

Figure 11.1 Challenges of bio-nanoparticles in six major industries are disc...

Guide

Cover

Table of Contents

Title Page

Copyright

Brief Biography of Editors

Preface

Begin Reading

Index

End User License Agreement

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Bio-Nanomaterials in Environmental Remediation

 

Industrial Applications

 

Edited by Narendra K. Sharma, Rekha Sharma, and

Tikam C. Dakal

 

 

 

 

 

Editors

Dr. Narendra K. SharmaBanasthali Vidyapith (Deemed University)Department of Bioscience and BiotechnologyTonk 304 022RajasthanIndia

Dr. Rekha SharmaBanasthali Vidyapith (Deemed University)Department of ChemistryTonk 304 022RajasthanIndia

Dr. Tikam C. DakalMohanlal Sukhadia UniversityDepartment of BiotechnologyUdaipur 313 001RajasthanIndia

Cover Image: © Bushko Oleksandr/Shutterstock

All books published by WILEY-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

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A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2025 WILEY-VCH GmbH, Boschstraße 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages, text and data mining and training of artificial technologies or similar technologies). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-35420-7

ePDF ISBN: 978-3-527-84853-9

ePub ISBN: 978-3-527-84852-2

oBook ISBN: 978-3-527-84854-6

Brief Biography of Editors

Dr. Narendra K. Sharma

Dr. Narendra K. Sharma is working as assistant professor at the Department of Biosciences and Biotechnology of the Banasthali Vidyapith, India. He has done a PhD from Defence Institute of Physiology and Allied Sciences, DRDO, India, and post-doctoral training from Guangzhou Institutes of Biomedicine and Health (GIBH), CAS, China, and Federal University of Sao Paulo (UNIFESP), Brazil. He has more than eight years of teaching and research experience. He has published more than 50 research articles in peer-reviewed international journals, books, and book chapters. He has presented his research work at various international conferences held in India, Brazil, China, USA, and Germany.

He has been conferred several prestigious awards including Dr. T S Vasundhara memorial best paper award, DRDO, Young Scientist and Best Innovator award by Microbiologist Society of India, nominated as best innovator by Indian Academy of neuroscience, and travel award from Japan Neuroscience Society.

Dr. Rekha Sharma

Dr. Rekha Sharma received her B.Sc. from the University of Rajasthan, Jaipur, in 2007. In 2012, she completed her M.Sc. in Chemistry from Banasthali Vidyapith. She was awarded a Ph.D. in 2019 by the same university under the supervision of Prof. Dinesh Kumar. Presently, she is working as an assistant professor in the Department of Chemistry, Banasthali Vidyapith, and has entered a specialized research career focused on developing water purification technology. With more than six years of teaching and research experience, she has published 16 articles in journals of international repute, 1 authored book with CRC Press, and over 60 book chapters in the field of nanotechnology. She has presented her work at more than 15 national and international conferences. Dr. Sharma has reviewed many renowned Journals, Elsevier, Bentham Science, and Springer Nature, Science Direct, Trends in Carbohydrate Research. She has been recognized as a Young Women Scientist by the Department of Science and Technology (DST), Government of Rajasthan. Her research interest includes developing water purification technology by developing biomaterial-reduced NPs and polymers and biopolymers incorporated metal oxide-based nanoadsorbents and nanosensors to remove and sense health-hazardous inorganic toxicants like heavy metal ions from aqueous media for water and wastewater treatment.

She has presented her work in more than 15 national and international conferences. Her research interest includes the development of water purification technologies by the fabrication of nanosensors and nano-adsorbents for water and wastewater treatment, and the remediation of microplastics.

Dr. Tikam C. Dakal

Dr. Tikam C. Dakal is currently working as an assistant professor at Department of Biotechnology, Mohanlal Sukhadia University (Rajasthan), India. Dr. Dakal pursued his PhD from the University of Modena and Reggio Emilia, Italy, and did post-doctoral training from University of Montreal (Canada) and University of Bordeaux (France). Dr. Dakal has also served as a Staff Scientist at Beckman Research Institute of the City of Hope, California (USA). He has more than 10 years of teaching and research experience. Currently, Dr. Dakal is working in the field of Genome and Computational Biology with a focus on analyzing the biological/clinical data for deciphering the molecular basis of complex pathologies, for instance, cancers, neurodegenerative disorders, and others.

Dr. Dakal has been listed among top-2% scientists of the world by Stanford University for past 3 years. Dr. Dakal has published over 100 research/review articles in reputed journals. He has also edited 1 book and published some book chapters in books from reputed publishers. Dr. Dakal is recipient of prestigious HMR Foundation Fellowship at University of Montreal (Canada) and FEMS-Young Scientist Award by VAAM, Germany.

Preface

“There’s Plenty of Room at the Bottom”-Richard Feynman. One of the biggest challenges facing the modern world is environmental pollution and degradation caused by several sources. Numerous conventional techniques and tools are being used to address this issue. The field of nanotechnology has witnessed remarkable advancements, revolutionizing various sectors across science, technology, industry, and environmental conservation. At the heart of this transformation lies the incredible potential of bio-nanomaterials engineered at the atomic or molecular scale. The book entitled “Bio-Nanomaterials in Environmental Remediation: Industrial Applications” edited by Dr. Narendra K. Sharma, Dr. Rekha Sharma, and Dr. Tikam C. Dakal explores some of the exciting applications of bio-nanomaterials across different domains. The present book is focused majorly on the application of bio-nanomaterials in different industrial applications. This book contains a detailed coverage of the classification, properties, synthesis, cutting edge applications, and future perspectives of bio-nanomaterials to enhance readers’ understanding. To attract a wider readership and achieve the overall goal, the first chapter of the book provides a description of fundamentals and an up-to-date overview of the main subject of this book, i.e., introduction to bio-nanomaterials. This book also will cover use of bio-nanomaterials in various industrial fields for the reader-free quantification of poisonous substances in water, the remarkable application of different bio-nanomaterials in water remediation, textile industry, oil industry, gas industry, food industry, and agriculture industry as well as in determination of hazard, toxicity, and monitoring standards of the bio-nanomaterials. Despite our best efforts, mistakes and misconceptions may have occurred, for which we apologize. We welcome constructive criticism and suggestions to improve the presentation.

    

Dr. Narendra K. Sharma

Dr. Rekha Sharma

Dr. Tikam C. Dakal

1Bio-nanomaterials: An Introduction

Abhinoy Kishore, Chaitanayajit Singh, and Gurpreet Kaur*

Department of Biotechnology, Chandigarh College of Technology, Chandigarh Group of Colleges (CGC), Landran, Mohali, Punjab

1.1 Introduction

A bio-nanomaterial encompasses a diverse array of biological molecules and components, such as proteins, antibodies, enzymes, nucleic acids, lipids, polysaccharides, oligosaccharides, viruses, and secondary metabolites, organized at the molecular level to form materials with unique properties and functions [1, 2]. Nanotechnology, a multidisciplinary domain focused on materials at the nanometer scale (1–100 nm), has experienced significant advancements in recent years [3]. This field has diverse applications that extend across a wide spectrum of scientific fields, demonstrating its extensive impact and significance. The term “nanotechnology” stems from the Greek word “nano,” denoting one-billionth of a meter, coined by Norio Taniguchi in 1974. This field has significantly advanced medicine by introducing nanosized particles and materials known for their exceptional biocompatibility and minimal toxicity, offering promising avenues for medical innovation and treatment. Bio-nanomaterials are the term assigned to nanosized materials, either composed of or produced through biological means. Nanoparticles, due to their minute size, exhibit extraordinary attributes across various domains including structure, chemistry, physics, optics, heat conductivity, mechanical strength, and electrical conductivity. Their distinctive characteristics position them as versatile tools in the biomedical sector, playing crucial roles in tasks such as advancing tissue engineering, regenerative medicine techniques, drug and gene delivery systems, cancer treatment modalities, and neurodegenerative disease therapies, thereby offering innovative solutions for addressing complex medical challenges [4]. For instance, drug delivery systems are designed to release drugs on target; gene therapy uses vectors that specifically enter targeted cells; cancer treatment employs nanoparticles (NPs) that selectively destroy tumor cells selectively; neurodegenerative diseases are addressed via therapeutic strategies that target specific pathological accumulations andinflammation is managed by therapeutic agents that regulate host immune responses among other possible causes of illnesses [5]. Furthermore, various bio-nanomaterials are utilized as diagnostic tools for identifying various biomarkers or as imaging agents for medical examinations.

Many biodegradable polymers and naturally sourced nanomaterials have been widely employed across biomedical, pharmaceutical, industrial, packaging, and agricultural sectors for the development of bio-nanomaterials. Manipulating materials at the nanoscale now enables fundamental interactions with biological systems, paving the way for customized medication delivery. This breakthrough opens avenues for precise and efficient illness treatment while minimizing adverse effects. Furthermore, bio-nanomaterials are essential in the creation of biosensors and imaging agents, which transform diagnostic methods and make it possible to identify various medical disorders early [6]. Hence, a wide array of biodegradable polymers and naturally derived nanomaterials have found extensive applications across diverse sectors, including biomedical, pharmaceuticals, industrial packaging, and agriculture (Figure 1.1). The utilization of bio-nanomaterials can be traced back to ancient Indian literature, particularly in Ayurveda, a traditional system of medicine practiced in the Indian subcontinent since the 7th century. Ayurvedic treatments often incorporate metal ash, known as Bhasma, to address various diseases [7]. Bhasma comprises metallic or mineral preparations that are treated with herbal juices or decoctions and subjected to specific heating processes, as outlined in the puta system of Ayurveda. Widely recommended across India, Bhasma, a form of bio-nanomaterial, is administered either alone or in combination with medicinal plant extracts or powders, depending on the specific therapeutic needs of the patient [8]. Bio-nanomaterials exhibit diverse applications in environmental remediation, offering significant potential to address various environmental challenges. Both natural and artificial bio-nanomaterials possess unique attributes that can be harnessed to develop efficient and durable remediation methods. These materials hold promise in reducing pollution, restoring ecosystems, and promoting sustainable environmental practices.

Figure 1.1 Applications of bio-nanomaterials. The figure illustrates the diverse range of applications of bio-nanomaterials across various fields, highlighting the versatility and potential impact of bio-nanomaterials, driving innovation and addressing pressing societal needs across diverse domains.

The chapter involves the types of bio-nanomaterials, the various kinds of bio-nanomaterial conjugates, and the application of bio-nanomaterials in various fields ranging from health care and sustainable environmental technologies.

1.2 Types of Bio-nanomaterials

Bio-nanomaterials could be the derivatives of macro biomolecules (biological NPs) or they could be organic or inorganic compounds synthesized via the mediation of biological materials (derived bio-nanomaterials) (Table 1.1).

1.2.1 Classification of Biological Nanoparticles

Biological NPs are classified into four major categories derived from biomolecules or synthesized from organic building blocks, i.e. proteins, nucleic acids, lipids, and polysaccharides.

1.2.1.1 Proteins

Proteins are polymers of amino acids and can be the predecessor for the production of NPs, specifically oligopeptides composed of 8–20 amino acids. Due to their unique functionalities and the defined primary structure, these peptides are used for surface modification and attachment of various compounds that might be used for drugs and therapeutics [41, 42]. The ability of protein to form gels, emulsions, and dried particles, along with their capacity to synthesize NP with controlled size distribution, make them novel candidates for NP synthesis [43]. There are a number of proteins used for the NPs formulation: gelatin, elastin, collagen, gliadin, zein, ferritin, albumin, and silk protein (sericin and fibroin) [44–46].

By integrating principles from physics, engineering, chemistry, and biology, we have harnessed the capability to engineer biological nanomaterials at the molecular scale, utilizing self-assembling peptide systems. Peptides serve as the building blocks for creating a diverse array of nanostructures, including but not limited to nanofibers, nanotubes, vesicles, nanometer-thick surface coatings, and nanowires. Self-assembling peptides play multifaceted roles, ranging from stabilizing membrane proteins to creating favorable environments for cell growth and tissue repair in regenerative medicine. Moreover, they aid in gene and drug delivery, showcasing their versatility as tools for crafting sophisticated architectures, innovative materials, and nanodevices. These capabilities drive advancements in nanobiotechnology and various engineering disciplines. Positioned at the intersection of various disciplines such as chemistry, materials science, molecular biology, and engineering, molecular self-assembly harnesses nature’s vast potential to advance across disciplines and enhance societal well-being. Nanofibers, elongated cylindrical structures measuring between 5 and 20 nm, possess a high surface-to-volume ratio that facilitates the incorporation of a wide array of bioactive molecules, including nucleic acids [47]. Among the peptides capable of self-assembly, examples include amyloid peptides, ionic self-complementary peptides, collagen-like triple helical peptides, and amphiphilic peptides, all of which can spontaneously organize into nanofibers [48].

Table 1.1 Overview of various strategies for biomolecule–nanoparticle integration.

S. no.

Material

Fabrication method

Particle size and characteristics

Application

References

 1

Bovine serum albumin (BSA)

Dynamic aggregation, radiation-induced cross-linking

20–40 nm

Drug carrier

[9

11]

 2

Cruciferin

Cold gelation

∼200 nm spherical, polydispersity index (PDI) of 0.2–0.3

Delivery of bioactive food components

[

12

,

13

]

 3

Chimeric polypeptide

Genetically encoded synthesis in E. Coli

60 nm, nearly monodisperse

Treatment of cancer Conjugated drug: paclitaxel

[14

16]

 4

Fibronectin

Electrospraying

28.2–31.52 nm

Functionally active protein for tissue engineering

[17

20]

 5

Zein

Electrospraying

175–900 nm

Encapsulant for food coloring and ingredients

[21

25]

 6

Fluorescent proteins

Liquid nanodispensing (NADIS)

50 nm–microns

Nanodevice (scanning probe lithography)

[26

28]

 7

Fibroin

Electrospraying

80 nm

Wound dressing and tissue engineering

[29

31]

 8

Whey protein isolate (WPI)

Homogenization-evaporation

90 nm

Delivery vehicle for beta-carotene to intestine

[26]

 9

Chitosan oligosaccharide/β-lactoglobulin

Ionic gelation

150–30 nm, spherical

Delivery of hydrophobic bioactive compounds into aqueous foods

[32

35]

10

Bioactive peptides/chitosan

Ionic gelation

151 ± 4.3 nm, PDI = 0.05–0.14

Encapsulant of epigallocatechin-3-gallate (EGCG) for nanochemoprevention

[

36

,

37

]

11

Chitosan

Ionic gelation

550–850 nm, spherical with some irregular shape particles

Protein carriers in tissue engineering

[38

40]

1.2.1.2 Nucleic Acid

DNA and RNA possess the remarkable capability to form controlled and three-dimensional-oriented NPs. Their inherent affinity for complementary sequences allows nucleic acids to self-assemble into intricate, multidimensional structures with particular control over size and shape. This self-assembling ability results in the formation of compact and stable NPs, offering a versatile platform for various applications in nanotechnology and biomedicine [49]. The versatility and inherent characteristics of nucleic acids enable the precise engineering of single-stranded DNA or RNA molecules, resulting in the formation of modular nucleic acid nanoparticles (NANPs). These NANPs offer the flexibility to be intricately tailored into elaborate three-dimensional structures composed entirely of nucleic acids. RNA and DNA molecules assemble into diverse higher-order structures through both canonical and noncanonical base pairings, serving as the foundation for creating a range of nanostructures such as rings, fibers, and polygons [50–52]. By carefully choosing nucleic acid components, NANPs can be fine-tuned to modify their physicochemical properties, biological activities, and versatility. In the realms of biotechnology and biomedicine, NANPs emerge as promising carriers for bioactive compounds, tools for molecular imaging and biosensing, scaffolds for biochemical reactions, and multifunctional NPs amalgamating diverse functionalities within a unified structure.

The expanding domain of nucleic acid nanotechnology has brought forth a multitude of synthesis protocols tailored for NANPs, along with established classification methodologies enabling their study both in controlled laboratory environments and within living organisms. Moreover, compelling proof-of-concept data has emerged, underscoring their potential across diverse therapeutic applications [53–55].

1.2.1.3 Lipids

The fragmentation of lipids can give rise to various nanostructures, including liposomes, nanoemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). These diverse lipid-based nanocarriers offer versatile platforms for drug delivery, enabling precise control over drug release kinetics, bioavailability, and targeting efficiency. These structures can be used for encapsulation of drugs to increase the efficiency by targeted delivery and preventing degradation of NPs [56, 57].

Liposomes, developed with an outer bilayer of amphipathic molecules like phospholipids enclosing an aqueous compartment, emerged as pharmaceutical products in the early nineties, with examples Alveofact® and Ambisome®. They possess several advantageous attributes as drug carriers: biological inertness, complete biodegradability, lack of toxicity, antigenicity, or pyrogenicity due to the natural presence of phospholipids in cell membranes. Additionally, liposomes can be tailored in terms of size, composition, and surface charge for specific applications, and they can encapsulate a wide range of hydrophilic and lipophilic drugs, offering possibilities for drug targeting. In the past two decades, SLNs, also known as lipospheres or nanospheres, have emerged as alternative particulate drug carrier systems, particularly suitable for lipophilic and poorly water-soluble drugs. With particle diameters ranging from approximately 10–1000 nm, SLNs combine the advantages of other carrier systems, including high biocompatibility, bioavailability, controlled release, physical stability, and protection of labile drugs from degradation. They are compatible with various administration routes such as oral, intravenous, pulmonary, and transdermal routes, thereby mitigating associated challenges [58].

1.2.1.4 Polysaccharides

Polysaccharides are a kind of carbohydrate polymers linked via glycosidic bonds. The most commonly used polysaccharide for NP is chitosan. Chitosan is a cationic polyaminosaccharide. Due to the presence of high-density amino groups and mucoadhesive properties, the reaction kinetics for the formation of new chemical bonds or negative complexation is very high [59]. The chitosan NPs easily conjugate with proteins, plasmid DNA, antigens, and bioflavonoids [60–62].

Polysaccharides, hydrophilic polymers derived from natural sources, are extensively employed in water-based polymer systems and nanotechnology owing to their advantageous attributes in biological settings. These include biodegradability, biocompatibility, and minimal toxicity, making them highly desirable for various applications. The exceptional properties of polysaccharides render them excellent candidates as building blocks for NP fabrication, particularly in medical therapy. The use of polysaccharides offers a plethora of benefits, such as high loading efficiencies, rapid drug release rates, precise targeting capabilities, remarkable stability, and minimal toxicity in physiological environments. Moreover, polysaccharides are abundant, easy to process, and derived from sustainable feedstocks, further enhancing their appeal. Chemical functionalization of polysaccharides, mainly via free carboxyl and hydroxyl groups, allows the creation of tailored polysaccharide derivatives with specific properties, facilitating their use in various applications. Various methodologies have been devised to synthesize polysaccharide-based NPs with precise control over size, morphology, and structure. These approaches encompass mechanisms such as ionic cross-linking, covalent cross-linking, self-assembly of hydrophobically modified polysaccharides, polyelectrolyte complexation, and the formation of polysaccharide–drug conjugates. The choice of synthetic route is crucial to optimize NP properties for specific applications, considering factors such as physicochemical parameters of polysaccharides, polysaccharide composition, NP size, and surface morphology. It is vital to note the distinction between NPs and nanocrystals, with NPs being amorphous particles and nanocrystals being crystalline, to avoid misunderstandings in terminology. While polysaccharide nanocrystals will not be discussed in detail, some useful applications will be mentioned [63].

1.2.2 Derived Bio-nanomaterials

There are various nanosized biomaterials that can be categorized as derived bio-nanomaterials. This is further categorized as the artificially synthesized nanomaterial mediated by biological compounds and the biological component which is part of organisms.

1.2.2.1 Green Synthesized Nanoparticles

Metal NPs can be developed via various chemical, physical, and radiation techniques. These methods encompass chemical reduction, precipitation, electrochemical deposition, sol-gel processes, physical vapor deposition, laser ablation, and irradiation-induced synthesis, among others. Each approach offers distinct advantages and allows for precise control over the size, shape, and properties of the resulting NPs, catering to specific applications in fields ranging from catalysis to biomedicine. The drawback associated with these methods is the potential for toxicity due to the use of certain chemicals, high temperatures, or radiation during the synthesis process. Metal and metal oxide NPs can be synthesized through the involvement of biological elements such as plant extracts, bacterial extracts, fungal extracts, seaweed, polysaccharides, biodegradable polymers, botanical materials, and algae. The green synthesis of NPs is a single-step process, environmentally benign, simple, economically viable, and clean technology as it does not involve harsh chemicals and zero harmful by-products. The biosynthetic pathways utilized for NP fabrication present a unique advantage by enabling the simultaneous reduction and stabilization of metal NPs within a single-step synthesis process [64].

1.2.2.2 Nanosize-Derived Component

Viruses, with sizes ranging from a few nanometers to hundreds of nanometers, present an intriguing avenue for various biomedical applications. Their surfaces can be modified and targeted for therapies such as cancer treatment, immune therapy, drug delivery, and detection. To date, only one viral therapy, T-VEC (Imlygic), a modified herpes simplex virus (HSV), has received Food and Drug Administration (FDA) approval for the treatment of cancer, specifically for subsets of patients with melanoma [65]. Viral nanoparticles (VNPs) encompass a diverse range of viruses, including plant viruses, bacteriophages, and mammalian viruses. Genome-free versions of VNPs, known as virus-like particles (VLPs), find utility in gene therapies, cancer therapies, antimicrobial therapies, immunotherapies, vaccines, cardiovascular therapies, imaging, and theragnostics [66].

1.3 Integration of Nanoparticles and Biomolecules

The size of biomolecules is comparable to NPs. The size similarity gives the advantage for the physical interaction with the NPs, which might lead to many noncovalent interactions such as ionic interaction, hydrophobic interaction, and solvation effect. Biomolecules, due to their intrinsic properties of donating electron clouds or accommodating excess negative charge, covalent bond formation, and stabilizing the volatile compound, lead to the formation of biomolecule–NP hybrids, which have characteristics of both NPs and biomolecules [67]. The intrinsic features of biomolecules could be used for the building block of NP architecture (Table 1.2). The protein molecules have various binding sites that could facilitate the development of multifunctional NPs [99].

1.3.1 Different Processes of Synthesis of Nanoparticles and Biomolecules Integration

1.3.1.1 Conjugation via Noncovalent Interactions

Noncovalent conjugation strategies are physical interactions involving electrostatic, hydrophobic, and affinity forces [100]. The ionic interaction between biomolecules and NPs offers a robust and stable approach to engineering desired complexes. This process involves either imparting the desired charge to NPs for binding with targeted biomolecules or binding biomolecules with charged ligands or specific buffers to enable binding with oppositely charged NPs [101]. For instance, to incorporate siRNA effectively, lipid NPs can be modified with supercharged coiled-coil arginine-rich proteins. This modification enables the NPs to interact with negatively charged RNA molecules, facilitating the encapsulation and delivery of siRNA for targeted gene silencing applications [102]. Another example is a self-assembled nanocomplex formed by negatively charged fucoidan (a sulfated polysaccharide) and positively charged protamine [103]. The advantage of a noncovalent electrostatic complex is the synergistic combination of functional properties of both.

Hydrophobic interaction also helps in binding of peptides onto the surface of silica at various pH conditions. By tuning the surface property of NPs and binding environment, the biomolecules adsorption on NPs can be regulated [104]. Similarly, gliadin, a protein NP can interact with Resveratrol via hydrophobic interaction [105].

1.3.1.2 Conjugation via Covalent Interactions

The covalent interaction that occurs between biomolecules and NPs is called chemisorption. In chemisorption, biomolecules having a thiol group (cysteine residue) can form a link with the NPs [106]. In instances where thiol residues are absent, a thiol group can be chemically introduced onto biomolecules using Traut’s reagent (2-aminothiolane). This reagent enables site-specific modification by reacting with primary amines, facilitating the attachment of thiol groups for subsequent conjugation or functionalization processes [106, 107]. Noble metal NPs, especially gold (Au), are highly reactive to the thiol group. Au can form a strong bond with sulfur (Au—S). This has been exploited in forming various conjugates of Au NPs of peptides, DNA, antibodies, and proteins [99, 100, 108].

Table 1.2 Various conjugation strategies and applications for nanoparticles conjugated with biomolecules.

S. no.

Biomolecule

Nanoparticle

Types of conjugates

Conjugation strategy

Application

References

1

Aptamers

AgNP/Fe

3

O

4

Biomolecule–hybrid nanoparticle conjugates

Streptavidin-biotin affinity binding

Detection of

Staphylococcus aureus

[68]

2

α-Amylase, pectinase, cellulose

Fe

3

O

4

Organic–inorganic nanoparticle conjugates

GA cross-linking

Clarification of fruit juices

[69]

3

AntHocyanin-rich extract

Whey protein isolate/beet pectin

Organic–organic nanoparticle conjugates

Electrostatic complexation

Encapsulation of natural colorants and food nutraceuticals

[70]

4

Bovine serum albumin (BSA)

Tripolyphosphate-cross-linked chitosan

Organic–organic nanoparticle conjugates

Electrostatic interaction, encapsulation

Sustained release of protein

[60]

5

PLGA, HPMA/Ac-DAPBoc

Biomolecule–polymeric nanoparticle conjugates

Coaxial electrospraying, one-pot synthesis

Delivery of platinum drugs into cancerous cells

[

71

,

72

]

6

Amphiphilic polymer-coated hydrophobic silver nanoparticles

Biomolecule–hybrid nanoparticle conjugates

Physisorption

To study protein-nanoparticle interaction

[73]

7

Copper(II) phosphate

Self-assembled biomolecule–nanoparticle hybrid

Decomposition of organic dyes in wastewater treatment

[74]

8

Beta-carotene

Whey protein concentrate

Organic–organic nanoparticle conjugates

Encapsulation

Encapsulation of bioactives

[75]

9

Chitosan

Polylactic acid/nifedipine

Biomolecule–polymeric nanoparticle conjugates

Encapsulation

Treatment of angina pectoris and hypertension

[75]

10

Bioactive glass

Organic–inorganic nanoparticle conjugates

Noncovalent

Injectable scaffolds in bone and cartilage repair

[76]

11

Cholesterol

Polyamidoamines

Biomolecule–polymeric nanoparticle conjugates

Covalent

Tamoxifen delivery

[77]

12

Cisplatin

PCL-block-PEGdiblock copolymer

Biomolecule–polymeric nanoparticle conjugates

Encapsulation

Treatment of glutathione over-expressed breast cancer cells

[78]

13

Curcumin

O

-Carboxymethyl chitosan/fucoidan

Organic–organic nanoparticle conjugates

Cross-linking

Oral delivery system

[79]

14

Zein–pectin/alginate

Organic–organic nanoparticle conjugates

Electrostatic interaction, encapsulation

Functional foods and beverages

[80]

15

Albumin–polycaprolactone

Biomolecule–hybrid nanoparticle conjugates

Covalent

Drug delivery system for prostate carcinoma therapeutics

[81]

16

DNA

Magnesium phosphate

Organic–inorganic nanoparticle conjugates

Entrapment

DNA vaccine formulation

[82]

17

(−)-epigallocatechin-3-gallate

Peptide/chitosan

Organic–organic nanoparticle conjugates

Encapsulation

Nano-chemoprevention

[83]

18

Glucose oxidase

Fe

3

O

4

/polypyrrole

Biomolecule–hybrid nanoparticle conjugates

Encapsulation

Potentiometric glucose biosensor

[84]

19

α-Lactalbumin and lipase

Copper(II) phosphate

Self-assembled biomolecule–nanoparticle hybrid

Biosensors

[85]

20

Hydroxyapatite-encapsulated-c-Fe2O3

Biomolecule–hybrid nanoparticle conjugates

Encapsulation covalent

Interesterification of soybean oil

[86]

21

Lysozyme and β-lactoglobulin

Silica

Organic–inorganic nanoparticle conjugates

Electrostatic interaction

Not specifically mentioned

[87]

22

Mussel adhesive proteins

Iron(III)-3,4-dihydroxyphenylalanine (DOPA)

Organic–inorganic nanoparticle conjugates

Cross-linking

pH-responsive drug delivery Model drug: Doxorubicin

[88]

23

Organic fluorescent dye

PVP/SiO

2

/Fe

3

O

4

Biomolecule–hybrid nanoparticle conjugates

Encapsulation Electrostatic interaction

Biomedical, analytical and catalytic application

[89]

24

Plasmid DNA

Calcium phosphate

Organic–inorganic nanoparticle conjugates

Encapsulation

Stem cell uptake and gene transfer

[90]

25

Pepsin

AuNP

Organic–inorganic nanoparticle conjugates

Covalent-amide coupling

Analytical sample preparation

[91]

26

Propolis

Lipid

Organic–organic nanoparticle conjugates

Entrapment

Nasal drug delivery

[92]

27

Quercetin

Chitosan oligosaccharide/β-lactoglobulin

Organic–organic nanoparticle conjugates

Covalent

Encapsulation of bioactives

[61]

28

Serum albumin

PCL/PLGA

Biomolecule–polymeric nanoparticle conjugates

Encapsulation

Delivery of therapeutics

[93]

29

Sericin

Copper(II) phosphate

Self-assembled biomolecule–nanoparticle hybrid

Adsorption of heavy metal ions

[94]

30

Spherical nucleic acid

AuNP

Organic-inorganic nanoparticle conjugates

Covalent

Cellular uptake

[95]

31

Sorafenib

PEG-PLGA/PLGA copolymer

Biomolecule–polymeric nanoparticle conjugates

Encapsulation

Systemic treatment of liver fibrosis

[96]

32

Trypsin

AuNP/Fe

3

O

4

Biomolecule–hybrid nanoparticle conjugates

Covalent

Enzymatic digestion of proteins to peptides

[97]

33

Xylanase

Fe

3

O

4

/SiO

2

Biomolecule–hybrid nanoparticle conjugates

Covalent

Enzymatic clarification of fruit juices

[98]

Low-molecular-weight bifunctional linkers are used to form a covalent linkage between biomolecules and NPs. These linkers encompass thiols, disulfides, and phosphine ligands, coupled with terminal functional groups such as carboxy, amino, or maleimide groups. They facilitate the conjugation of biomolecules to common NPs, including Au (gold), CdS, ZnS, CdSe/ZnS, and Ag (silver), enabling the formation of stable complexes for various biomedical and nanotechnological applications [101, 106].

1.3.2 Organic–Organic Nanoparticle complexes

Biological NPs have the capability to form complexes with other biological NPs through encapsulation. These encapsulated bio-nanomaterials find numerous applications across industries such as food, pharmaceuticals, and cosmetics. For instance, β-carotene, a highly photosensitive compound, can be encapsulated within whey protein concentrate (WPC) using techniques such as electrospraying. The resulting nanocomplex of β-carotene/WPC exhibits exceptional stability against photo-oxidation, making it suitable for various applications in food and pharmaceutical formulations [75].

Similar encapsulation strategies can be followed for bioactive molecules such as curcumin, quercetin, and (−) epigallocatechin-3-gallate (EGCG). These highly unstable compounds are encapsulated with chitosan-based NPs. Chitosan NPs are more stable as compared to chitosan, so the encapsulation is better in the case of NPs as compared to whole chitosan [61, 79, 83].

1.3.3 Biomolecule–Polymer Nanoparticle Complexes

Biocompatible and biodegradable polymers such as poly(ethylene glycol) (PEG), poly(lactic acid) (PLA), polyglycolides (PGA), poly(lactide-co-glycolides) (PLGA), polycaprolactone (PCL), and poly(hydroxy butyrate) (PHB) are extensively employed due to stimulus-responsive properties and robust mechanical strength. These polymers are utilized in the fabrication of biomolecule–polymer conjugates, resulting in nanostructures suitable for drug delivery applications [109–111].

The complex formed between a polymer and biomolecules usually consists of two layers: an outer shell comprising biocompatible biomolecules and an inner shell composed of a hydrophobic polymer that can encapsulate drugs. A prime example of such a complex nanostructure is the FDA-approved thermoplastic hydrophobic polymer poly-methyl methacrylate (PMMA) combined with bovine serum albumin (BSA) [112]. Employing the nanoprecipitation technique, particles of 100 nm size are synthesized, with their dimensions and surface charge controlled by adjusting the concentration of BSA and PMMA. Encapsulation of the hydrophobic drug camptothecin showcased improved antitumor efficacy.

1.3.4 Organic–Inorganic Complex

Inorganic NPs, such as metals, metal oxides, and quantum dots, exhibit unique optical, electronic, and catalytic properties. Their conjugation with biomolecules such as DNA, enzymes, antibodies, and peptides plays a crucial role in pharmaceutical industries, therapeutics, and diagnostics. Among these, gold (Au) NPs are extensively studied. The surface chemistry of gold NPs is meticulously regulated through the utilization of biomolecules, opening avenues for the advancement of next-generation nanoscale complexes. For instance, Au NPs hybridized with the fungal protein hydrophobin (HFB) Vmh2 yield stable HFB–AuNP complexes. These complexes can effectively interact with biomolecules such as BSA and immunoglobulins, offering promising applications in various biomedical and diagnostic fields [113].

Similarly, enzymes can be integrated onto the surface of inorganic NPs, which results in a highly stable enzyme complex [114]. For instance, when pepsin is bound to Au NPs via amide coupling, it forms a stable and efficient biocatalyst. This biocatalyst has applications in the analysis of therapeutic proteins and peptides, showcasing the versatility and potential of Au NP–biomolecule conjugates in various biomedical and pharmaceutical contexts [91]. Moreover, these complexes offer the advantage of incorporating multiple enzymes into a single NP. For example, a multienzyme complex comprising alpha-amylase, pectinase, and cellulase can be functionalized onto magnetic NPs. This enables the clarification of fruit juice turbidity, demonstrating the potential of enzyme-functionalized NPs in various industrial applications, particularly in food processing and beverage production [69].

1.3.5 Self-Assembled Biomolecule–Nanoparticle Complex

Self-assembly is an innovative technology wherein various components of an integrating complex are fabricated in a desired order. A study demonstrated that when proteins are incorporated into nanostructure construction, it results in the formation of flower-like nanostructures. This exemplifies the power of self-assembly techniques in engineering complex and functional nanomaterials with tailored properties for diverse applications in nanotechnology and biomedicine [115]. Indeed, the formation of flower-like nanostructures is attributed to protein-induced nucleation of copper phosphate crystals during the self-assembly process. Similarly, self-assembly phenomena are observed in DNA nanostructures. The complementary nature of DNA strands allows for the precise and facile manipulation of size and shape in these self-assembled nanostructures. This inherent programmability makes DNA nanostructures a versatile platform for engineering complex and customizable nanomaterials with tailored functionalities for a wide range of applications in nanotechnology and biomedicine. Geometrically nanostructured shapes have been developed for various applications, including DNA cubes, knots, polyhedra, and nanotubes. These DNA nanostructures are utilized for mechanical motions and computational studies, showcasing the versatility and potential of DNA-based nanotechnology in engineering intricate and functional nanomaterials for diverse applications in nanotechnology, biomedicine, and beyond [116].

Peptide self-assembly has emerged as a promising field in nanomedicine, offering diverse benefits for biomedical applications [117–121]. By employing rational design strategies, various peptide-based supramolecular architectures such as micelles, vesicles, and nanofibers can be synthesized, with each structure being governed by noncovalent interactions [47]. The inherent amphiphilicity of peptides, with polar and nonpolar regions, facilitates their self-assembly through microphase separation [122, 123]. Noncovalent interactions, including hydrophobic and ionic interactions, van der Waals forces, hydrogen bonds, and π–π stacking, serve as the primary driving forces for self-assembly [122]. For gene delivery, peptide nanoassemblies consist of hydrophobic amino acids driving self-assembly, hydrophilic amino acids.

Peptide self-assembly has emerged as a promising avenue in nanomedicine, owing to the manifold benefits offered by well-defined applications Nanoassemblies, derived from common amphiphilic peptides and peptide conjugates [117–121], encompass a range of supramolecular structures suitable for biomedical applications. These structures include linear, ionic complementary, long-chain alkylated, and lipo-peptides [124]. In contrast to individual peptides, peptide self-assemblies exhibit distinctive attributes such as multivalent binding, dynamic cargo interactions, responsiveness to environmental and cellular stimuli, and prolonged functionality. Through a systematic design of molecular building blocks, various peptide-based supramolecular architectures – such as micelles, vesicles, nanofibers, nanotubes, and NPs – can be synthesized [125]. The inherent amphiphilicity of peptides, with polar and nonpolar regions, facilitates their self-assembly through microphase separation [122, 123].

Various noncovalent interactions, such as hydrophobic and ionic interactions, van der Waals forces, hydrogen bonds, and π–π stacking, serve as the primary driving forces behind self-assembly [122]. For instance, aromatic residues predominantly contribute to self-assembly through π–π stacking, while hydrogen bonding plays a crucial role in the formation and stabilization of secondary structures. Peptides exhibiting stable β-strand conformations have the propensity to form extended β-sheet structures through lateral connections, crucial for the formation of nanofibers and nanotubes. Within these β-sheets, hydrophobic side chains align in one direction, while polar side chains align in the opposite direction [126]. Conversely, α-helical structures promote the formation of micelles and vesicles, where hydrogen bonding occurs between the carbonyl group of one amino acid and the amino group of four residues down the peptide chain. The outward orientation of amino acid side chains in α-helices enables interactions [125]. Well-defined peptide nanoassemblies for gene delivery comprise three fundamental components: hydrophobic amino acids facilitate self-assembly through intermolecular noncovalent interactions and subsequent secondary structure formation; hydrophilic amino acid residues stabilize the structure in a biological environment; and positively charged amino acid residues interact electrostatically with negatively charged nucleic acids [47]. In contrast, peptide NPs, referred to as peptiplexes, spontaneously form via electrostatic interactions between positively charged peptide residues (lysine, arginine, and histidine) and negatively charged nucleic acids [127].

Furthermore, chemical structures of peptides are engineered to yield nanoassemblies tailored specifically for diagnostic imaging [128], focusing on two crucial aspects: the peptide’s targeting property and functionalization with a detectable moiety [129]. This approach leverages the unique properties of peptides to design and fabricate nanomaterials with precise control over size, shape, and surface properties, enabling their use as contrast agents for various imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging. These peptide-based nanoassemblies hold promise for improving the sensitivity and specificity of diagnostic imaging techniques, facilitating early disease detection and monitoring.

The self-assemblies result in various structures. Vesicles, spherical hollow structures delimited by bilayers, are formed from one or more types of amphiphilic molecules [125]. Hydrophilic regions are oriented toward both inner and outer aqueous environments, while hydrophobic residues pack together between these hydrophilic interfaces [130]. Consequently, vesicles have the capability to encapsulate hydrophilic molecules within their interior aqueous phase and hydrophobic molecules within the hydrophobic regions of the bilayer [131]. Modifying the composition and chain length of the building blocks enables the adjustment of the size of vesicles [132]. Self-assembly of pure amphiphilic oligopeptides [133] and diblock copolypeptides [134, 135] results in the formation of vesicles in aqueous solution. The propensity of peptides to assemble into vesicles or nanotubes is largely influenced by the hydrophobicity of their tails. Additionally, surfactant-like peptides featuring a hydrophilic head domain comprise aspartic acid residues and a hydrophobic tail composed of 4–10 glycine residues have been observed to self-assemble into vesicles with diameters of approximately 30–50 nm [136, 137].

Peptide-based nanovesicles provide several advantages over liposomes, including enhanced membrane fluidity, targeting ability, biocompatibility, and stability, attributed to the inherent chemical and biological properties of peptides [138, 139]. Peptide-mediated targeting and safeguarding cargo against extracellular threats are particularly critical for in vivo DNA delivery. Improving DNA stability and extending circulation time facilitate superior organ distribution [140, 141].

Self-assembled peptide vesicles (SPVs) undergo diverse chemical modifications, including conjugation of other peptides or bioactive molecules to the outer surface as well as encapsulation of specific cargoes within the aqueous cavity or the hydrophobic domain of the membrane [142, 143]. An example of such a multifunctional SPV platform involves the conjugation of the epidermal growth factor receptor (EGFR) binding peptide GE11 to glycidyl hexadecyl dimethyl ammonium chloride (GHDC).

Peptide nanotubes (PNTs) represent intricate three-dimensional structures, maintaining a distinct hollow cylindrical form through molecular interactions among their amphiphilic building blocks [144]. These PNTs offer vast potential for functionalization, particularly at the head group of peptide amphiphiles, making them versatile candidates for diverse applications [145]. As the hydrophobic alkyl chains align toward the core and the amino acid residues toward the outer surfaces, functional groups become accessible on the outer surfaces of PNTs [146].

Peptide-based micelles, considered one of the leading self-assembly nanostructures in biomedicine, comprise closed monolayers characterized by a hydrophobic inner core encased within a hydrophilic outer shell. Two primary methods for micelle preparation are direct dissolution and solvent switch. The spontaneous formation of these precisely structured spherical assemblies, with a narrow size distribution, takes place above a critical micellar concentration (CMC) and may be influenced by temperature [147, 148].

Figure 1.2 Classification of bio-nanomaterials. The figure presents a classification scheme for bio-nanomaterials based on their composition, structure, and synthesis methods. This classification scheme provides a comprehensive overview of the diverse landscape of bio-nanomaterials, guiding future efforts toward innovative applications and solutions.

Overall classification of bio-nanomaterials is represented in Figure 1.2.

1.4 Application of Bio-nanomaterials

1.4.1 Clinical Application

The plethora of research focused on the development of various types of bio-nanomaterials has led to a rise in the number of therapeutics for both diagnosis and treatment of diseases. These advancements have propelled the field of nanomedicine forward, offering innovative solutions for targeted drug delivery, imaging, and diagnostics. As a result, bio-nanomaterials hold great promise for improving patient outcomes and revolutionizing healthcare practices in the near future. The lipid NP-encapsulated drug delivery shows better drug release and it is targeted to the specific area. This precise drug delivery minimizes the possibility of side effects and reduces the frequency of drug administration [149].

Cancer Treatment and Diagnosis

: There are a number of studies to develop bio-nanomaterials to combat cancer. In one study, a bio-nanomaterial is synthesized using gold NP packed with effector protein (SipA), from

Salmonella enterica

. Bio-nanomaterials have demonstrated the ability to suppress tumor growth by effectively reducing the expression of P-glycoprotein, a multidrug resistance transporter, at significantly lower doses compared to free SipA. This reduction in P-glycoprotein expression enhances the effectiveness of chemotherapeutic agents, showcasing the potential of bio-nanomaterials in overcoming drug resistance mechanisms and improving the efficacy of cancer treatments

[150]

. The surface resonance property of Gold NPs’ is utilized to target and bind to prostate cancer biomarkers, causing a detectable change in their SPR(surface plasmon resonance) characteristics. This alteration, measured through techniques such as spectrophotometry, enables accurate and minimally invasive diagnosis of prostate cancer, promising improved patient outcomes through early detection. Gold NP is conjugated with prostate-specific antibodies (PSAs) and when these particles bind to the cancer cells, the NPs come together and show color change due to surface plasmon resonance

[151]

. Protein and polysaccharides have the potential to be used as vehicles in NP-mediated delivery systems [

83

,

152

]. Antioxidant phytochemicals can be effectively encapsulated within bio-nanomaterials, facilitating their targeted delivery without compromising their anticancer properties.

Encapsulating EGCG with biocompatible NPs derived from bioactive peptide/chitosan greatly improves EGCG’s bioavailability, enhancing its potential therapeutic effects. This innovative approach improves the delivery of EGCG, a potent antioxidant found in green tea, by protecting it from degradation and improving its absorption in the body. This encapsulation strategy holds promise for enhancing the therapeutic potential of EGCG in various biomedical applications [83]. Bio-nanomaterial-based carriers enable the simultaneous delivery of multiple drugs, leading to a synergistic effect. This approach is especially advantageous in cancer therapy, as tumor microenvironments, with their pH gradients, present challenges for conventional drug delivery. Encapsulation within bioactive peptide/chitosan NPs enhances EGCG’s efficacy by overcoming these barriers, potentially improving cancer treatment outcomes. To address this, pH-responsive drug delivery systems have been developed, employing mussel adhesive protein (MAP)-based iron (III)-3,4-dihydroxyphenylalanine (DOPA) NPs. These systems capitalize on the pH sensitivity of MAPs and DOPA to trigger drug release in the acidic tumor microenvironment, thereby boosting the effectiveness of cancer therapies while reducing unintended side effects [153].

The shape of NPs plays a significant role in therapy, especially in applications such as bone regeneration. NPs synthesized from gelatin and hydroxyapatite with a spherical topology have been found to enhance bone formation compared to other shapes. This can be attributed to their capacity to mimic the natural structure of bone minerals, fostering interactions with bone cells and thereby enhancing osteogenesis and bone regeneration more efficiently. Such findings underscore the importance of NP shape in tailoring therapeutic outcomes and optimizing treatments for specific biomedical applications [154]. Bio-nanoparticles possess the potential to supplant traditional carriers in drug delivery applications. Utilizing protein NPs as drug carriers has demonstrated the ability to facilitate efficient transport across the blood–brain barrier, addressing a pivotal challenge in the treatment of neurological disorders. These protein NPs offer several advantages, including biocompatibility, targeted delivery, and the ability to encapsulate and protect drugs from degradation. Researchers are leveraging the distinctive properties of bio-nanoparticles to develop more efficient and precisely targeted therapies for neurological disorders [155].

1.4.1.1 Drug Delivery System

Protein cages are intricate structures formed by the self-assembly of individual protein monomers, distinct from viral components. They include VLPs and VNPs, each with unique characteristics. VLPs lack viral genomes and are considered noninfectious, potentially eliciting different immunostimulatory responses compared to VNPs. These structures, comprising repeating protein subunits, offer high multivalency. Plant viruses can exhibit spherical/icosahedral or filamentous/tubular shapes. Viruses, with their innate ability to carry nucleic acids, serve as optimal vehicles for drug delivery. They offer versatility in binding active molecules through infusion, encapsulation, absorption, or conjugation to protein interfaces, ensuring protection and enabling precise targeting of the intended site of action [66].

Although clinically approved nanomedicines based on plants or bacteriophages are currently absent, numerous candidates are undergoing preclinical development, with several progressing toward translational development. Prominent platforms include tobacco mosaic virus (TMV), cowpea mosaic virus (CPMV), cowpea chlorotic mottle virus (CCMV), physalis mottle virus (PhMV), potato virus X (PVX), and bacteriophages such as MS2, P22, Qβ, and M13. Ranging in size from approximately 30 nm to over a micron, these viruses exhibit diverse shapes. Advancements in biochemistry and directed evolution techniques have propelled the development of viral nanocarriers for drug delivery, imaging, and theranostic applications. This review underscores the utilization of VNPs and VLPs in diverse biomedical domains, spanning antimicrobial treatments, cancer therapies, protein/peptide delivery, gene therapies, monotherapy, and combination cancer treatments as well as vaccines for infectious diseases, cancer, and other conditions. Additionally, it explores their role in imaging modalities and theranostics, integrating photothermal therapy (PTT) [66].

1.4.1.2 Lipid-Based Approved Nanopharmaceuticals

Liposomes, as pioneering drug delivery systems, remain widely utilized due to their versatile composition, biocompatibility, biodegradability, and lack of immunogenicity. These artificial phospholipid vesicles typically range from 50 to 100 nm in size, with anionic, cationic, or neutral variants, and feature a central aqueous phase. While liposomes predominantly encapsulate hydrophilic drugs within their aqueous core, they can also accommodate hydrophobic drugs in their bilayer or chemically attach them to the particles. In contrast, micelles, another phospholipid-based structure, possess a hydrophobic core ideal for encapsulating hydrophobic drugs and are employed for targeted drug delivery to specific sites, thereby reducing bio sdistribution toxicity.

The initial generation of liposomes exhibited limitations in blood circulation time and tumor tissue-specific targeting due to uptake by the mononuclear phagocyte system (MPS), leading to accumulation primarily in the liver and spleen. However, advances in lipid selection and modification techniques, such as sterically stabilizing nanoliposomes with sphingomyelin/choline (SM/CHO) and coating with PEG, known as pegylated or Stealth liposomes, have overcome these challenges. Pegylated liposomes demonstrate prolonged circulation time, enhanced extravasation through leaky tumor vasculature via passive targeting, reduced uptake by reticuloendothelial system (RES) cells, and decreased drug leakage in circulation. These modifications facilitate drug accumulation in tumor tissue, significantly improving upon the limitations of the first generation of liposomes.

Various lipid-based nanotechnology platforms have yielded approved nanopharmaceuticals, with Doxil™ being the first FDA-approved in 1995, followed by Caelyx™ and Myocet™, which encapsulate the chemotherapeutic doxorubicin. These formulations, including pegylated and nonpegylated versions, were developed to mitigate the high cardiotoxicity associated with doxorubicin. By extending circulation time and reducing distribution volume, they enhance tumor uptake through the enhanced permeability and retention (EPR) effect, improving tumor therapy efficacy. DaunoXome™ encapsulates Daunorubicin, protecting it from degradation and enhancing its accumulation in tumors, particularly indicated for advanced HIV-associated Kaposi’s sarcoma. Mepact™, an immunomodulator, is indicated for treating high-grade resectable nonmetastatic osteosarcoma. Ameluz™, a nanoemulsion gel containing 5-aminolaevulinic acid, is activated by red light to treat actinic keratosis. Marqibo™, an NP formulation of Vincristine, reduces neurotoxicity and is indicated for advanced acute lymphoblastic leukemia. Onivyde™, encapsulating Irinotecan, is indicated for metastatic adenocarcinoma of the pancreas. Vyxeos™, a liposomal formulation of Daunorubicin and Cytarabine, is used for high-risk acute myeloid leukemia treatment. These nanopharmaceuticals showcase the versatility and efficacy of lipid-based nanotechnology in drug delivery [156].

1.4.1.3 Protein-Based Approved Nanopharmaceuticals

Protein-based NPs present numerous advantages, including biocompatibility and biodegradability, with fibroin and albumin frequently employed. They have the capacity to transport diverse therapeutic agents, encompassing genetic materials, anticancer drugs, and peptide hormones. Several protein-based NPs have received approvals from the FDA and EMA for cancer treatment. Examples include OncasparTM for acute lymphoblastic leukemia, OntakTM for cutaneous T cell lymphoma, and AbraxaneTM and PazenirTM for metastatic breast cancer and other solid tumors. These NPs provide targeted delivery, reducing toxicity and enhancing antitumor activity. Additionally, KadcylaTM, an antibody–drug conjugate, is approved for HER2-positive breast cancer. Overall, protein-based NPs show promise for advanced cancer therapy, with numerous options approved by regulatory agencies [157, 158].

Peptide-based micelles offer distinct advantages in gene delivery, such as remarkable stability, efficient gene loading capability, and small size, enabling effective tumor penetration and cellular uptake. Cationic micellar nanoassemblies efficiently condense nucleic acids, exemplified by cationic peptide dendrimers and amphiphilic peptides, which exhibit superior delivery efficacy compared to conventional transfection agents. These micelles are customizable to target specific cells, promoting cellular uptake, facilitating endosomal escape, and enabling transport to the nucleus. Amphiphilic cationic peptides self-assemble into micelles with robust DNA-binding affinity, effectively shielding DNA and elevating gene expression levels in contrast to alternative complexes. These peptides exhibit a dual nature, with hydrophobic and hydrophilic regions, enabling the formation of stable micellar structures that efficiently encapsulate DNA. This unique architecture enhances the protection of DNA payloads during transportation and facilitates their delivery to target cells, ultimately leading to heightened gene expression levels. Peptide constituents offer the versatility to engineer vesicles responsive to environmental cues or external triggers. For instance, cationic vesicles containing drugs like Doxorubicin exhibit pH-triggered cargo release, while pH- and temperature-sensitive vesicles derived from specific copolypeptides respond to variations in their surroundings. Additionally, surfactant-like peptides have the capacity to self-organize into nanotubes, forming robust hierarchical architectures conducive to gene delivery owing to their positively charged characteristics. Hybrid nanotubes combining peptides with polymers or lipids are being investigated for diverse biomedical purposes, particularly in gene delivery, capitalizing on their nontoxic attributes and adaptable architectures. These hybrids offer a synergistic combination of the unique properties of peptides with the functionalities of polymers or lipids, enhancing their efficacy and versatility in biomedical applications.