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NANOMATERIALS AND NANOTECHNOLOGY IN MEDICINE
A comprehensive introduction to nanomaterials and their application in the field of medicine
The use of nanotechnology and nanomaterials more generally is an emerging field that has generated a lot of interest in the last few years. To this point, there have been few books that deal with the recent advances in nanomaterials or nanocomposites in the medical discipline.
Intended as a one-stop reference, Nanomaterials and Nanotechnology in Medicine provides the reader with the most-up-to-date and comprehensive exploration of the field of nanomedicine. The scope of the topic is huge, with nano applications in every medical specialization—from diagnostics to pharmaceuticals, from biological therapies to surgical devices, and from regenerative therapies to gene therapy. As such, this volume provides the most comprehensive coverage of this intriguing field of study.
Nanomaterials and Nanotechnology in Medicine readers will also find:
- An application-oriented book dedicated towards helping researchers find solutions to both fundamental and applied problems
- Chapters written by leading researchers from industry, academy, government, and private research institutions across the globe
Nanomaterials and Nanotechnology in Medicine is a useful reference for medical doctors, medical practitioners, post-doctoral research fellows, senior graduate students, and medical libraries.
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Table of Contents
Cover
Title Page
Copyright Page
List of Contributors
Preface
1 Nanomaterials and Nanotechnology in Medicine
1.1 Nanoneurology
1.2 Nanomolecular Diagnostics
1.3 Nanopharmaceuticals
1.4 Role of Nanotechnology in Biological Therapies
1.5 Nanomaterials for Gene Therapy
1.6 Nanotools for the Treatment of Ocular Diseases
1.7 Nanotechnology Applications in Food and Nutrition Science
1.8 Rubber Nanocomposites for Biomedical Applications
References
2 Nanoneurology
2.1 Introduction and Recent Advances
2.2 Types of Nanomaterials
2.3 Nanomaterial Applications for Neurodegenerative Diseases
2.4 Nanomaterial Applications for Strokes
2.5 Nanomaterial Applications for Spinal Cord Injuries
2.6 Nanomaterial Applications for Brain Tumors
2.7 Adverse Effects of Nanomaterials
2.8 Regulatory Issues
2.9 Conclusions
References
3 Nanomolecular Diagnostics
3.1 Introduction
3.2 Nanodiagnostics
3.3 Nanoparticles for Molecular Diagnostics
3.4 Applications of Nanoparticles for Molecular Diagnostics
3.5 Comparison Between Nanomaterials and Other Materials in Molecular Diagnostics
3.6 Prospects of Nanodiagnostics
3.7 Regulatory Issues
3.8 Conclusion
References
4 Nanopharmaceuticals
4.1 Introduction
4.2 Liposomes in Nanopharmaceuticals
4.3 Polymeric Nanoparticles in Nanopharmaceuticals
4.4 Solid Lipid Nanoparticles in Nanopharmaceuticals
4.5 Dendrimers in Nanopharmaceuticals
4.6 Quantum Dots in Nanopharmaceuticals
4.7 Regulatory Issues
4.8 Conclusion
References
5 Role of Nanotechnology in Biological Therapies
5.1 Introduction
5.2 Biological Therapies
5.3 Nanoparticles in Biological Therapies
5.4 Application of Nanotechnology in Biological Therapies
5.5 Advantages and Disadvantages of Nanoparticles in Biological Therapies
5.6 Conclusion
References
6 Nanomaterials for Gene Therapy
6.1 Introduction and Recent Advances
6.2 Nanomaterials and their Physicochemical Properties
6.3 Methods of Characterizing the Physicochemical Properties of Nanomaterials
6.4 Target Organ Biocompatibility/Toxicity
6.5 Gene Delivery
6.6 Regulatory Issues
References
7 Nanotools for the Treatment of Ocular Diseases
7.1 Introduction
7.2 Ocular Anatomy
7.3 Physiological Barriers in the Eye
7.4 Methods of Ocular Disease Treatment
7.5 Nanomedicine in Ocular Therapy
7.6 Closing Remarks
Conflict of Interest
References
8 Nanotechnology Applications in Food and Nutrition Science
8.1 Introduction
8.2 Nanostructured Delivery Systems
8.3 Nanoparticles Based on Inorganic Materials
8.4 Metal Nanoparticles
8.5 Conclusion
References
9 Rubber Nanocomposites for Biomedical Applications
9.1 Introduction
9.2 Rubbers for Biomedical Applications
9.3 Rubber‐based Nanocomposites
9.4 Conclusions
References
10 Nanomaterials and Nanotechnology in Medicine
10.1 Nanomaterials and Scaffolds for Tissue Engineering and Regenerative Medicine
10.2 Nanorobotics in Nanomedicine
10.3 Nanosensors
10.4 Inorganic Nanoparticles for Drug‐delivery Applications
10.5 Intelligent Nanomaterials for Medicine
10.6 Polymer‐based Nanocomposites for Biomedical Applications
10.7 Toxicity of Nanomaterials
10.8 Multifunctional Nanomaterials for Medical Applications
10.9 Antimicrobial Applications of Nanoparticles
References
11 Nanomaterials and Scaffolds for Tissue Engineering and Regenerative Medicine
11.1 Introduction and Recent Advances
11.2 Tissue Engineering and Regenerative Medicine: General Concepts
11.3 Implantable Nanomaterials to Regenerate Living Tissues
11.4 Nanomaterials as Carriers for Therapeutic Agents
11.5 Nanofibrous Scaffolds
11.6 Nano‐topography Techniques for Tissue‐engineered Scaffolds
11.7 Regulatory Issues
11.8 Conclusion
References
12 Nanorobotics in Nanomedicine
12.1 Introduction
12.2 What is Nanorobotics?
12.3 Nanorobotics in Nanomedicines
12.4 Nanorobots for Medical Imaging
12.5 Nanorobots for Targeted Drug Delivery
12.6 Enzymatic Nanolithography
12.7 Biomimetic Approach
12.8 Cell Biochips
12.9 Nanorobots for Precision Surgery
12.10 Nanorobots for Detoxification
12.11 Fabrication of Nanorobots
12.12 Toxicity
12.13 Administration and Retrieval
12.14 Clinical Presence of Nanorobots
12.15 Reproducibility and Standardization
12.16 Regulatory Issues
12.17 Conclusion
References
13 Nanosensors
13.1 Introduction and Recent Advances
13.2 Classification of Nanosensors
13.3 Nanosensor Fabrication
13.4 Inorganic Nanosensors
13.5 Biopolymer‐derived Nanosensors
13.6 Applications
13.7 Regulatory Issues
13.8 Conclusions
References
14 Inorganic Nanoparticles for Drug‐delivery Applications
14.1 Introduction
14.2 Synthesis of Inorganic Nanoparticles
14.3 Properties of Inorganic Nanoparticles
14.4 Functionalization of Inorganic Nanoparticles
14.5 Quantum Dots for Drug Delivery
14.6 Drug Delivery by Mesoporous Silica Nanoparticles
14.7 Silver Nanoparticles for Drug Delivery
14.8 Gold Nanoparticles for Drug Delivery
14.9 Superparamagnetic Iron Oxide Nanoparticles for Drug Delivery
14.10 Hybrid Systems of Inorganic Nanoparticles
14.11 Prospects of Inorganic Nanoparticles
14.12 Conclusion
References
15 Intelligent Nanomaterials for Medicine
15.1 Introduction to Intelligent Nanomaterials
15.2 Design and Function of Intelligent Nanoparticles
15.3 Various Intelligent Materials for Medicines
15.4 Type of Stimuli in Intelligent Nanomaterials in Medicine
15.5 Clinical Applications of Intelligent Nanomaterials
15.6 Potential Risk Factors in Nanomaterial Application
15.7 Summary and Future Prospects
References
16 Polymer‐based Nanocomposites for Biomedical Applications
16.1 Introduction and Recent Advances
16.2 Polymers for Biomedical Fields
16.3 Synthesis of Nanocomposites
16.4 Characterization Tools for Nanocomposites
16.5 Size, Shape, and Morphology of Nanocomposites
16.6 Polymer Nanocomposites for Various Applications
16.7 Nanocomposites for Molecular Diagnosis and Biopharmaceutics
16.8 Perspectives of Nanocomposites
16.9 Conclusion
References
17 Toxicity of Nanomaterials
17.1 Introduction and Recent Advances
17.2 Biomedical Applications of Nanomaterials
17.3 Biodistribution, Mechanism, and Excretion of Nanomaterials
17.4 Toxicity of Nanomaterials
17.5 Physicochemical Properties and Toxicity of Nanomaterials
17.6 Regulatory Issues
17.7 Conclusion
References
18 Multifunctional Nanomaterials for Medical Applications
18.1 Introduction and Recent Advances
18.2 Multifunctional Nanomaterials
18.3 Diagnostic Application
18.4 Therapeutic Application
18.5 External Stimuli‐responsive Nanoparticles for Medicinal Applications
18.6 Regulatory Issues
18.7 Conclusion and Future Perspectives
References
19 Antimicrobial Applications of Nanoparticles
19.1 Introduction
19.2 Antimicrobial Properties of Nanoparticles
19.3 Antimicrobial Applications of Nanoparticles
19.4 Conclusions
References
Index
End User License Agreement
List of Tables
Chapter 4
Table 4.1 Number of studies completed by condition involving the administra...
Table 4.2 Number of studies completed by region involving the administratio...
Table 4.3 Examples of polymer‐based nanopharmaceuticals available in the wo...
Chapter 5
Table 5.1 Some ligands used in targeted therapy with NPs and their correspo...
Table 5.2 Polymeric, lipidic, and micellar NPs in clinical trials.
Table 5.3 Radiotherapeutic nanosystems evaluated in preclinical studies.
Chapter 6
Table 6.1 Physicochemical properties of nanomaterials.
Chapter 8
Table 8.1 Types of nano‐functional food delivery systems [17, 18].
Table 8.2 The overview of different types of nanoparticles and their applic...
Table 8.3 Different nanocomposite formulations of curcumin/nano curcumin an...
Table 8.4 The molecular mechanisms involved in the main carotenoids of saff...
Chapter 11
Table 11.1 Parameters affecting the electrospun fiber morphology.
Table 11.2 Different methods applied to generate nonpatterns onto surfaces....
Chapter 12
Table 12.1 Comparison of imaging technique for detecting nanorobots.
Table 12.2 Summary of
in vivo
application of nanorobots based on a source o...
Chapter 13
Table 13.1 List of patents filed on nanosensor evolution.
Chapter 18
Table 18.1 Clinically approved nanoparticle‐based therapeutics [108].
Chapter 19
Table 19.1 Antimicrobial activity of MeONPs toward various microorganisms....
Table 19.2 Antimicrobial activity of some MeNPs toward microorganisms.
List of Illustrations
Chapter 2
Figure 2.1 Schematic structure of the BBB.
Figure 2.2 Schematic structures of nanomaterials used for CNS delivery.
Figure 2.3 Schematic representation of stroke core and penumbra.
Figure 2.4 Top: Schematic representation of the nanoparticles and methodolog...
Figure 2.5 Nanoconjugate composition determines degree and locus of BBB pene...
Figure 2.6 Radiation primes glioblastoma for SLN targeted delivery. (a) Mice...
Figure 2.7 Anti‐glioma effects of IUdR/NGO/SPION/PLGA + MF vs IUdR/NGO/SPION...
Figure 2.8 Suggestion of nanotoxicological classification system.
Chapter 3
Figure 3.1 Applications of nanoparticles in molecular diagnostics.
Chapter 4
Figure 4.1 Nanopharmaceuticals in drug delivery.
Figure 4.2 Methods for the preparation of polymeric nanoparticles.
Figure 4.3 Attractive features of SLNPs represented on the left side and rea...
Figure 4.4 Schematic representation of dendrimer components.
Figure 4.5 Schematic representation of a quantum dot.
Chapter 5
Figure 5.1 Main strategies in AuNP‐conjugates for biological therapy [78, 81...
Figure 5.2 Superparama‐gnetic NPs as promising tools in cancer therapy.
Figure 5.3 Lanthanide NPs; preparation strategies for medical applications....
Chapter 7
Figure 7.1 Schematic representation of (a) the sagittal section of the human...
Figure 7.2 The main physiologic barriers in ocular drug delivery.
Figure 7.3 Delivery routes for the main methods of drug administration in th...
Figure 7.4 Main nanoparticle properties influencing their application and pe...
Figure 7.5 Interaction of the different radiation ranges (according to the I...
Chapter 8
Figure 8.1 Examples of the different types of nanocarriers.
Figure 8.2 The structure of a colloidsome.
Figure 8.3 Example of a possible nanolaminate material formed from a globula...
Figure 8.4 Chemical structure of dendrimers.
Figure 8.5 The chemical structure of curcumin. It is a powder found in the g...
Figure 8.6 The solubility of the nanocurcumin particles (CURNs) (left) and c...
Figure 8.7 The chemical structure of PLGA.
Figure 8.8 The chemosensor for mercury determination in water samples using ...
Figure 8.9 The chemical structure of bioactive compounds present in
Crocus s
...
Figure 8.10 Comparison of the size of various selenium forms and selenium na...
Chapter 9
Figure 9.1 (a) General structure of silicone rubber (b) structure of PDMS.
Figure 9.2 Synthesis of segmented poly(ether‐urethane) and poly(ether‐uretha...
Figure 9.3 Fluorescence micrographs of preosteoblast nuclei stained with Hoe...
Figure 9.4 Low‐ and high‐magnification scanning electron micrographs of preo...
Figure 9.5 Metabolism of preosteoblasts on SR and SR–nHA composite quantifie...
Figure 9.6 Scheme of preparation of Ag/PTFE coatings onto silicone rubber su...
Figure 9.7 Live/dead fluorescent images of adhered (left)
Escherichia coli
a...
Figure 9.8 (a) Illustrative diagrams of the
in vitro
bladder model; (b) comp...
Figure 9.9 Fabrication of shape memory scaffolds by 3D printing using a low‐...
Figure 9.10 Structure of scaffolds. [50] Wang, Y. J., et. al., (2018), Figur...
Figure 9.11 (a) Schematics of hMSC seeding procedure (b) Fluorescent images ...
Figure 9.12 Appearance of the ETNR/SRC film containing 30% SRC and the ETNR/...
Chapter 11
Figure 11.1 Engineered nanostructured scaffolds for human tissues.
Figure 11.2 Tissue engineering utilizes ECM‐mimicking scaffolds, mammalian c...
Chapter 12
Figure 12.1 Schematic representation of activated nanorobotics at the cellul...
Figure 12.2 Cumulative publications on the nanorobotics in nanomedicines....
Figure 12.3 Outline of therapeutic perceptions in nanorobotics for
in vivo
h...
Figure 12.4 Schematic representation of steps involved in repairing cells.
Figure 12.5 Schematic representation of a mechanical platelet, clottocyte, t...
Figure 12.6 Schematic representation of target delivery of magnetically driv...
Figure 12.7 Schematic representation of different factors considered in the ...
Figure 12.8 Schematic representation of RBCs‐Mg Janus micromotor mobilized i...
Figure 12.9 Schematic drawing of the photolithographic stages.
Figure 12.10 Pie chart representing the estimated ratio of the route of admi...
Chapter 13
Figure 13.1 A schematic view of nanosensors.
Figure 13.2 Electron hopping phenomenon (a) before bonding, (b) after bondin...
Figure 13.3 Gold nanoparticles covered in casein. Proteases eat the protecti...
Figure 13.4 Exhaled breath analysis.
Figure 13.5 MOFs in gas sensing.
Figure 13.6 Comparison of top‐down and bottom‐up approach.
Figure 13.7 Lithography and fiber pulling process.
Figure 13.8 Molecular beam epitaxy process.
Figure 13.9 Emission of a photon (UV) is higher than that of the incident ph...
Figure 13.10 Tyrosine Kinase activity for DNA.
Figure 13.11 Quantum dots used in cancer diagnostic and stem cell therapy.
Figure 13.12 Behavior of nanosensor toward fluorescence, i.e. implanted in s...
Figure 13.13 Protein and DNA detection in nanosensors.
Figure 13.14 Process of biomarker identification.
Figure 13.15 Share of nanosensor applications in global market.
Chapter 14
Figure 14.1 (a) Schematic representation of pH‐responsive DOX‐loaded zinc ox...
Figure 14.2 Various targeting approaches to targeted cancer therapy.
Figure 14.3 (a) Schematic representation of necessary features MSNPs for sti...
Figure 14.4 (a) Schematic representation of the mechanism of antimicrobial a...
Figure 14.5 (a) Mechanism of DOX‐tethered AuNPs' drug delivery.(b) AuNPs...
Figure 14.6 Schematic representation of FA conjugated SPIONs for tumor thera...
Chapter 15
Figure 15.1 Various nanocarrier platforms in medicine industries.
Figure 15.2 Categorization of the drug‐delivery platform of smart nanostruct...
Figure 15.3 Triggering media in intelligent nanomaterials in medicine.
Chapter 16
Figure 16.1 Some of the most useful polymers' chemical structure for biomedi...
Figure 16.2 Types and classification of nanocomposite materials [2, 6, 10]....
Figure 16.3 Types of nanocomposite materials used for drug delivery and othe...
Figure 16.4 (a) and (c) are images of complex nanocarrier composite particle...
Figure 16.5 TEM micrograph (a) corresponds to a polymer–polymer nanocomposit...
Figure 16.6 SEM micrograph (a) Corresponds to polymer (PCL)‐
b
‐(Gly) aggregat...
Figure 16.7 Various applications of polymer‐based nanocomposites in broader ...
Figure 16.8 Biomedical applications of polymer‐based nanocomposites [30–35]....
Figure 16.9 The drug‐loaded nanocomposite and release upon structural disint...
Figure 16.10 The drug release kinetics for different pore sized nanomaterial...
Chapter 17
Figure 17.1 The utilization of nanomaterials in biomedical applications.
Figure 17.2 Clearance of nanoparticles from different organs.
Figure 17.3 Different shapes of nanoparticles.
Chapter 18
Figure 18.1 General applications of multifunctional nanomaterials.
Figure 18.2 (a) Schematic illustration of the synthesis of multifunctional C...
Figure 18.3 Types of nanodevices used in clinical applications [93].
Figure 18.4 Schematic illustration of stimuli‐responsive MNP‐based DDSs for ...
Figure 18.5 (a) Histological observation of the tumor tissues after differen...
Figure 18.6
In vitro
and
in vivo
MRI of Fe
3
O
4
@Dex‐TPP/PpIX/ss‐mPEG. (a) Tran...
Figure 18.7 Schematic illustration of the synthetic process of COF‐Au‐MnO
2
‐H...
Figure 18.8 Temperature‐ and pH‐dependent cumulative release of erlotinib fr...
Figure 18.9 (a) Photograph of tumors on day 12 after different treatments. (...
Figure 18.10 Schematic representation of the real‐time monitoring of ATP‐res...
Chapter 19
Figure 19.1 Overview of antimicrobial mechanisms by MeONPs [53].
Guide
Cover Page
Title Page
Copyright Page
List of Contributors
Preface
Table of Contents
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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Nanomaterials and Nanotechnology in Medicine
Edited by
Dr. P.M. Visakh
Assistant Professor, Department of Physical Electronics
TUSUR University,
Tomsk, Russia
This edition first published 2023© 2023 John Wiley & Sons Ltd
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Library of Congress Cataloging‐in‐Publication Data
Names: P. M., Visakh, editor.Title: Nanomaterials and nanotechnology in medicine / edited by Dr. P.M. Visakh, Assistant Professor, Department of Physical Electronics, TUSUR University, Tomsk, Russia.Description: Hoboken, NJ : Wiley, 2022. | Includes bibliographical references and index.Identifiers: LCCN 2022027360 (print) | LCCN 2022027361 (ebook) | ISBN 9781119558033 (hardback) | ISBN 9781119558040 (adobe pdf) | ISBN 9781119558095 (epub)Subjects: LCSH: Nanomedicine. | Nanotechnology. | Nanostructured materials–Therapeutic use. | Medical technology.Classification: LCC R857.N34 N25643 2022 (print) | LCC R857.N34 (ebook) | DDC 610.285–dc23/eng/20220802LC record available at https://lccn.loc.gov/2022027360LC ebook record available at https://lccn.loc.gov/2022027361
Cover Design: WileyCover Image: © Volodymyr Horbovyy/Shutterstock
List of Contributors
Elham AbohamzehDepartment of Energy, Materials, andEnergy Research Center (MERC)Karaj, Iran
Chander AmgothDepartment of ChemistryZhejiang UniversityHangzhou, China
António Francisco AmbrósioUniversity of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine Coimbra, PortugalandUniversity of Coimbra Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, PortugalandClinical Academic Center of Coimbra (CACC) Coimbra, PortugalandAssociation for Innovation and Biomedical Research on Light and Image (AIBILI) Coimbra, Portugal
V.K. Ameena ShirinCollege of Pharmaceutical SciencesGovernment Medical CollegeKozhikode, Kerala, India
Saritha AppukuttanDepartment of ChemistryAmrita Vishwa VidyapeethamKollam, Kerala, India
Liliana Aranda LaraFacultad de MedicinaUniversidad Autónoma del Estado de MéxicoToluca, Estado de México, Mexico
Ehsan AryanAntimicrobial Resistance Research CenterDepartment of Medical Bacteriology and Virology, Qaem University HospitalSchool of Medicine, Mashhad University of Medical SciencesMashhad, Iran
Hongzhen BaiDepartment of ChemistryZhejiang UniversityHangzhou, China
Francesco BainoInstitute of Materials Physics and EngineeringDepartment of Applied Science and Technology, Politecnico di TorinoTorino, Italy
Ajit BeheraDepartment of Metallurgical & Materials EngineeringNational Institute of TechnologyRourkela, Odisha, India
Asit BeheraSchool of Mechanical Engineering, KIITBhubaneswar, India
Rupali S. BhadaleShobhaben Pratapbhai Patel School of Pharmacy and Technology Management SVKM’s NMIMSMumbai, Maharashtra, India
Elisa J. CamposUniversity of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine Coimbra, PortugalandUniversity of Coimbra Center for Innovative Biomedicine and Biotechnology (CIBB) Coimbra, PortugalandClinical Academic Center of Coimbra (CACC), Coimbra, Portugal
António CamposUniversity of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine Coimbra, PortugalandUniversity of Coimbra Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, PortugalandClinical Academic Center of Coimbra (CACC) Coimbra, PortugalandDepartment of Ophthalmology, CentroHospitalar Leiria E.P.E., Leiria, PortugalandciTechCare, Center for Innovative Care and Health Technology, Polytechnic Institute of Leiria, Leiria, Portugal
Shuai ChenDepartment of ChemistryZhejiang UniversityHangzhou, China
D. Dharun Daniel RajDepartment of BiotechnologyMaulana Abul Kalam Azad University of TechnologyHaringhata, West Bengal, IndiaMoataz A. Elsawy Polymer Laboratory, Petrochemical DepartmentEgyptian Petroleum Research Institute Nasr City, Cairo, Egypt
Anila FariqDepartment of BiotechnologyUniversity of KotliAzad and Jammu Kashmir, PakistanandDepartment of BiotechnologyFatima Jinnah Women UniversityRawalpindi, Pakistan
Guillermina Ferro‐FloresDepartamento de Materiales RadiactivosInstituto Nacional de Investigaciones NuclearesOcoyoacac, Estado de México Mexico
Jayalatha GopalakrishnanDepartment of Polymer Science and Rubber TechnologyCochin University of Science and TechnologyKochi, Kerala, India
Eggehard HollerNanomedicine Research Center in the Department of NeurosurgeryCedars Sinai Medical CenterLos Angeles, CA, USA
Keila Isaac‐OlivéFacultad de MedicinaUniversidad Autónoma del Estado de MéxicoToluca, Estado de México, MexicoLiron L. IsraelNanomedicine Research Center in the Department of NeurosurgeryCedars Sinai Medical CenterLos Angeles, CA, USA
Jitha S. JayanDepartment of ChemistryAmrita Vishwa VidyapeethamKollam, Kerala, India
Kuruvilla JosephDepartment of ChemistryIndian Institute of Space Science and TechnologyValiyamala, Kerala, India
Saeid KargozarTissue Engineering Research Group (TERG), Department of Anatomy and Cell BiologySchool of MedicineMashhadUniversity of Medical SciencesMashhad, Iran
V. KarthikDepartment of BiotechnologyK.S. Rangasamy College of TechnologyTiruchengode, Tamil Nadu, India
Farzad KermaniDepartment of Materials EngineeringFaculty of EngineeringFerdowsi University of Mashhad (FUM)Mashhad, Iran
Gerardo Leyva‐GómezFacultad de QuímicaUniversidad Nacional Autónoma de MéxicoCiudad de México, Mexico
Vaishali Y. LondheShobhaben Pratapbhai Patel School of Pharmacy and Technology ManagementSVKM’s NMIMS, MumbaiMaharashtra, India
Nancy Evelyn Magaña VergaraFacultad de Ciencias QuímicasUniversidad de ColimaColima, Mexico
João MartinsUniversity of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of MedicineCoimbra, PortugalandUniversity of CoimbraCenter for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, PortugalandClinical Academic Center of Coimbra (CACC) Coimbra, PortugalandUniversity of Coimbra, Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS) Coimbra, Portugal
Néstor Mendoza MuñozFacultad de Ciencias Químicas, Universidad de ColimaColima, Mexico
Zahra MeshkatAntimicrobial Resistance Research CenterDepartment of Medical Bacteriology and Virology, Qaem University HospitalSchool of MedicineMashhad University of Medical SciencesMashhad, Iran
Majid G. MobarhanMetabolic Syndrome Research CenterSchool of MedicineMashhad University of Medical SciencesMashhad, IranMohamed H. MostafaPolymer Laboratory, Petrochemical DepartmentEgyptian Petroleum Research Institute Nasr City, Cairo, Egypt
S.S. MohapatraDepartment of Mechanical EngineeringNIT Rourkela, Odisha, India
Ranjan K. MohapatraDepartment of ChemistryGovernment College of EnginneringKeonjhar, Odisha, India
Enrique Morales‐AvilaFacultad de QuímicaUniversidad Autónoma del Estado de MéxicoToluca, Estado de México, Mexico
T.G.N. NagarjunDepartment of Food TechnologyK.S. Rangasamy College of TechnologyTiruchengode, Tamil Nadu, India
Simin NazarnezhadTissue Engineering Research Group (TERG)Department of Anatomy and Cell BiologySchool of MedicineMashhad University of Medical SciencesMashhad, Iran
Blanca Ocampo‐GarcíaDepartamento de Materiales RadiactivosInstituto Nacional de Investigaciones NuclearesOcoyoacac, Estado de México, Mexico
S. PoornimaDepartment of BiotechnologyK.S. Rangasamy College of TechnologyTiruchengode, Tamil Nadu, India
K. PramodCollege of Pharmaceutical SciencesGovernment Medical CollegeKozhikode, Kerala, India
David Quintanar‐GuerreroFacultad de Estudios Superiores CuautitlánUniversidad Nacional Autónoma de MéxicoMexico, Mexico
Ramya RajanDepartment of ChemistryAmrita Vishwa VidyapeethamKollam, Kerala, India
Majid RezayiMedical Toxicology Research CenterMashhad University of Medical SciencesMashhad, IranandDepartment of Medical Biotechnology and Nanotechnology, School of MedicineMashhad University of Medical SciencesMashhad, Iran
Kobra S. RiziAntimicrobial Resistance Research Center Department of Medical Bacteriology and Virology, Qaem University Hospital School of MedicineMashhad University of Medical SciencesMashhad, IranandDepartment of Medical Biotechnology and Nanotechnology, School of MedicineMashhad University of Medical SciencesMashhad, Iran
Chinnu SabuCollege of Pharmaceutical SciencesGovernment Medical CollegeKozhikode, Kerala, India
A.K. SahooSchool of Mechanical EngineeringKIITBhubaneswar, India
Renu SankarCollege of Pharmaceutical SciencesGovernment Medical CollegeKozhikode, Kerala, India
M. SaravananAMR and Nanotherapeutics LaboratoryDepartment of PharmacologySaveetha Dental College Saveetha Institute of Medical and Technical Sciences Chennai, India
Ayesha SelhabaDepartment of BiotechnologyUniversity of KotliAzad and Jammu Kashmir, Pakistan
Ahmad ShafeePublic Authority of Applied Education & Training, College of Technological StudieApplied Science DepartmentShuwaikh, Kuwait
M. SheikholeslamiDepartment of Mechanical EngineeringBabol Noshirvani University of TechnologyBabol, IranandRenewable energy systems and nanofluid applications in heat transfer LaboratoryBabol Noshirvani University of TechnologyBabol, Iran
R. SubbaiyaDepartment of Biological SciencesSchool of Mathematics and Natural SciencesThe Copperbelt UniversityRiverside, Kitwe, Zambia
Guping TangDepartment of ChemistryZhejiang UniversityHangzhou, China
P. M. VisakhDepartment of Physical ElectronicsTUSUR UniversityTomsk, Russia
A. VigneshwaranSchool of Biosciences and TechnologyVellore Institute of TechnologyVellore, Tamil Nadu, India
Azra YasminDepartment of BiotechnologyFatima Jinnah Women UniversityRawalpindi, Pakistan
Kaxi YuDepartment of ChemistryZhejiang UniversityHangzhou, China
Anum ZulfiqarDepartment of BiotechnologyFatima Jinnah Women UniversityRawalpindi, Pakistan
Preface
This book, Nanomaterials and Nanotechnology in Medicine, summarizes recent research accomplishments in the area of nanomedicine. It discusses topics such as: challenges and opportunities, nanoneurology, nanomolecular diagnostics, nanopharmaceuticals, the role of nanotechnology in biological therapies, nanomaterials for gene therapy, nanomaterials in ophthalmology/ocular diseases, nanonutrition, rubber‐based nanocomposites for biomedical applications etc. The book is intended to provide a valuable reference source for university and college faculties, professionals, post‐doctoral research fellows, senior graduate students, researchers, and medical doctors. The various chapters in this book are written by prominent researchers from industry, hospitals, academia, and government and private research laboratories across the globe. It provides an up‐to‐date record of the major findings and observations in the field of nanomedicine.
Chapter 1 provides an overview of the main points of the various chapters by focusing on scope, state‐of‐the‐art, applications, new challenges and opportunities of nanomedicine. The second chapter describes important applications of nanoneurology. In this chapter the author introduces the topic and discusses recent advances in nanomaterials and their application in: neurodegenerative diseases; nanomaterial application for stroke; nanomaterial application for spinal cord injury; nanomaterial application for brain tumor; the potential adverse effects of nanomaterials in nanoneurology; and regulatory issues.
Nanodiagnostics, nanoparticles for molecular diagnostics, the comparison between nanomaterials and other materials in molecular diagnostics, and the prospects of nanodiagnostics are described in Chapter 3. The fourth chapter focuses on nanopharmaceuticals. In this chapter, after the introduction and identification of recent advances, the authors discuss the following topics: liposomes in nanopharmaceuticals, polymeric nanoparticles in nanopharmaceuticals, solid lipid nanoparticles in nanopharmaceuticals, dendrimers in nanopharmaceuticals, and quantum dots in nanopharmaceuticals. The role of nanotechnology in biological therapies is the emphasis in the fifth chapter. In this chapter, the authors address different topics such as biological therapies, nanoparticles in biological therapies, application of nanotechnology in biological therapies, and the advantages and disadvantages of nanoparticles in biological therapies.
The sixth chapter's focus is gene therapy and includes nanomaterials and their physicochemical properties, target organ biocompatibility/toxicity, and gene delivery. The following chapter concentrates on nanomaterials in ophthalmology and ocular diseases. In this chapter, the author explains ocular anatomy, physiological barriers in the eye, methods of ocular disease treatment, and the use of nanomedicine in ocular therapy. Nanonutrition, the focus of Chapter 8, covers topics such as nanostructured delivery systems, nanoparticles based on inorganic materials, and metal nanoparticles. Rubber‐based nanocomposites provide the subject content for Chapter 9 and includes discussion of biomedical applications for rubber‐based nanoparticles including their applications and their use in nanocomposites.
Chapter 10 provides an overview of the materials development of nanoparticles and the challenges and opportunities encountered including the scope and state‐of‐the‐art of nanomedicine. The next chapter, 11, describes the past, present, and future aspects of nanomedicine, that is, research and education in nanomedicine. In discussing tissue engineering and regenerative medicine the authors cover the general concepts, implantable nanomaterials to regenerate living tissues, nanomaterials as carriers for therapeutic agents, nanofibrous scaffolds, and nanotopography techniques for tissue‐engineered scaffolds. The authors of Chapter 12 address a wide range of topics under the umbrella of nanorobotics. This includes nanorobots in: nanomedicine; medical imaging; targeted drug delivery; enzymatic nanolithography; a biomimetic approach; cell biochips; precision surgery; and detoxification. They further discuss the fabrication, toxicity, administration and retrieval of nanorobots as well as the clinical presence of nanorobots and their reproducibility and standardization. Chapter 13's focus is on nanosensors and their application where the authors discuss the classification and fabrication of nanosensors, and inorganic and biopolymer‐derived nanosensors.
Inorganic nanoparticles for drug‐delivery applications are addressed in Chapter 14. This chapter contains explanations and discussions of the synthesis of inorganic nanoparticles, as well as inorganic nanoparticles' properties and functionalization, and drug delivery by: quantum dots; mesoporous silica nanoparticles; silver, gold, and iron oxide nanoparticles. Also contained in this chapter is a consideration of hybrid systems and the prospects for inorganic nanoparticle applications. Chapter 15 introduces intelligent nanomaterials, including: their design and function; the range for medicines; and the type of stimuli required in medicine as well as their clinical applications and potential risk factors in use.
Polymer‐based nanocomposites, Chapter 16, addresses topics such as: polymers for biomedical fields, the synthesis of nanocomposites; characterization tools for nanocomposites; the size, shape, and morphology of nanocomposites, and polymer nanocomposites for various applications including use in molecular diagnosis, biopharmaceutics. Chapter 17 considers the effect of the toxicity and physiochemical properties of nanoparticle applications and includes discussion of the biodistribution, mechanism, and excretion of nanomaterials. The following chapter, Chapter 18, focuses on multifunctional nanoparticles in medical applications. The authors discuss diagnostic and therapeutic application, and external‐stimuli responsive nanoparticles as part of their account. The authors in the final chapter provide information on and discussion of the antimicrobial properties and applications of nanoparticles.
Finally, I would like to express my sincere gratitude to all the contributors of this book, who provided excellent support in the successful completion of this venture. I am grateful to them for the commitment and the sincerity they have shown toward their contributions in the book. Without their enthusiasm and support, the compilation of book could have not been possible. I would like to thank all the reviewers who have taken their valuable time to make critical comments on each chapter. I also thank John Wiley & Sons for recognizing the demand for such a book, and for realizing the increasing importance of Nanomaterials and Nanotechnology in Medicine and for starting such a new project area.
Dr. Visakh P. M.
1Nanomaterials and Nanotechnology in Medicine : Medical Applications: Challenges and Opportunities
P. M. Visakh
Department of Physical Electronics, TUSUR University, Tomsk, Russia
1.1 Nanoneurology
In principle, nanosystems with surface modifications can provide blood‐brain barrier (BBB)‐crossing, imaging, and therapeutic treatment especially in the case of surface‐modified, encapsulating nanosystems. They can also reduce off‐target effects. Frequently, nanosystems are designed to combine ample targeting, imaging, and drug loads designed for high functional capacity. In many cases, disease pathology can cause the impairment of the BBB. For example, in brain tumors or metastasis, rapid angiogenesis in the growing tumor results in leaky vessels. The phenomenon that distinguishes tumor from healthy vessels is known as the enhanced permeability and retention effect (EPR) [1, 2].
The main medicinal applications for nanomaterials are imaging and therapy that require targeted delivery. Nanomaterials can be applied in separate or combined “theranostic” fashion since nanomaterials can often carry multiple functionalities. More frequently, targeting moieties are attached to a nanosystem for tracking the administered drug and its safety to unfold its pharmaceutical activity only at the intended site and avoid side (“off‐target”) effects.
Therapeutic agents that can be delivered by nanotechnology or that are under investigation vary from low molecular weight molecules such as synthetic pharmaceuticals and peptides and high molecular weight proteins such as antibodies, enzymes, and, most challenging, nucleic acids. The mechanisms underlying treatments are versatile as well and may include immunotherapy, photodynamic therapy, thermotherapy, and gene delivery. Nanoparticles, which include micelles, dendrimers, and spheres, are often being studied for central nervous system (CNS) delivery. Micelles [3] are spherical structures of amphiphilic molecules that are organized in accordance with their hydrophobic tail forming the core and their hydrophilic head contacting the aqueous solvent. In contrast with polymers of linear platforms, dendrimers are repetitively branched nanomolecules.
Another type of nanomaterial includes carbon nanotubes (CNTs), consisting of a crosslinked carbon–carbon structure. Members of the fullerene structural family are allotropes of carbon with a cylindrical nanostructure, either single‐ or multi‐walled involving entirely sp2‐hybrid carbon atoms. Since they have unique properties, in term of strength as well as electrical (semiconductors), optical, and thermal properties, they are also studied for BBB delivery, as well as fullerenes of spherical structure. The biocompatibility is disputed. In recent years, cell‐derived delivery systems have been studied for CNS delivery. One example is the “nanoghost” (NG) system [4, 5].
Using mostly but not exclusively mesenchymal stem cells [45–48], these derived vesicles are prepared by physical (e.g., sonication) and chemical treatment of cells to remove cytoplasm and nuclei leaving a small (~200 nm) membrane compartment that has inherited targeting capabilities from the “mother” cell. Current NGs are derived from cancer stem cells to treat tumors. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common types, and some other examples include Huntington's disease, amyotrophic lateral sclerosis (ALS), prion disease, tauopathies, and several types of non‐AD dementia, which is a collective term used to describe various symptoms of cognitive decline. Unlike other neurodegenerative diseases such as PD, where there are treatments available, the complexity of AD leads to the fact that to date, only the symptoms are treatable and there is no cure for the disease. As the age of the population is on the rise, so is the number of people who will be affected by the disease in older age [6]. Therefore, AD is one of the most studied neurodegenerative diseases.
Studies suggest that passive diffusion across the BBB may be reduced due to a thickened basement membrane and that the BBB paracellular route remains unaffected, potentially lowering the ability of nanomedicines to cross AD BBB; therefore, the extent of BBB disruption in AD remains controversial [7]. In another study, magnetic Fe3O4 nanoparticles coated with oleic acid molecules were used as a nanocarrier loaded with α‐synuclein RNAi plasmid [8].
N‐isopropylacrylamide derivative (NIPAm‐AA) was photo‐immobilized onto the oleic acid molecules, and short hairpin RNA (shRNA) was absorbed. The same method was used to absorb nerve growth factor (NGF) to NIPAm‐AA to specifically promote neuronal uptake via NGF receptor‐mediated endocytosis.
PD, is another neurodegenerative disease characterized by a progressive loss of dopaminergic neurons and an elevated level of intracytoplasmic Lewy bodies (abnormal aggregates of α‐synuclein protein) in the remaining neurons located in the substantia nigra (SN) pars compacta, a region of the midbrain. This loss of neurons is accompanied by the death of astrocytes and a significant increase in the number of microglia in the SN. In order to study both the mechanism and drug delivery for PD, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is often used to facilitate PD in mice. In a recent study, graphene quantum dots (GQDs) were used to prevent α‐synucleinopathy in PD by inhibiting fibrillization of α‐syn and interacting directly with mature fibrils [9].
For that purpose, GQDs were synthesized by placing carbon fibers in a mixture of strong acid. Initial tests showed that in the absence of GQDs, α‐syn monomers assembled into mature fibrils, while the GQDs predominantly inhibited α‐syn fibrillization. GQDs also induced the dissociation of α‐syn fibrils into short fragments. In a study, a functionalized nanogel‐based nanovector was selectively internalized in activated mouse or human astrocytes [10]. The nanogel was based on two main polymers, polyethylene glycol 8000 and linear polyethylenimine 2500. Rolipram, an anti‐inflammatory drug, when administered by these nanovectors, limited the inflammatory response in A1 astrocytes, reducing iNOS and Lcn2, which in turn reverses the toxic effect of proinflammatory astrocytes on motor neurons in vitro, showing advantages over conventionally administered anti‐inflammatory therapy. Nanoscale immunoconjugates (NIC) treatment of mice bearing intracranial GL261 glioblastoma (GBM) results in an increase of CD8+ T cells, NK cells, and macrophages with a decrease of regulatory T cells (Tregs) in the brain tumor area. Survival of GBM‐bearing mice treated with NIC combination is significantly longer compared to animals treated with single checkpoint inhibitor‐bearing NICs or free a‐CTLA‐4 and a‐PD‐1. The same polymeric backbone was also used to deliver antisense oligo nucleotides (AONs) against extracellular matrix (ECM) laminins [11].
One example are iron oxide NPs, which may be used for heat therapy in brain tumor systems [12]. The increased temperature in the tumor can reach a certain temperature which can cause cell death, but also recruit the local immune system to fight the tumor or influence gene expression [13, 14]. However, not all iron oxide particles will reach the target. Some will be cleared mainly to the liver by macrophages via the reticuloendothelial system (RES).
1.2 Nanomolecular Diagnostics
Molecular diagnostics is defined as the detection of genomic variations for the diagnosis, prediction, and monitoring feedback of therapy. The integration of genomics, molecular biology techniques, and laboratory medicine has led to the foundation of molecular diagnostics. Together these elements provide accurate characterization of inherited diseases essential for an accurate diagnosis. High‐throughput next‐generation sequencing methods and genome‐wide association studies provide instrumental discernments into the disease mechanisms and allow physicians to assess disease predilection, devise precise diagnostic methods, and personalize a cure [15]. In recent years, the advancement of molecular technologies has remarkably accelerated the growth of molecular diagnostics. Diagnostic molecular biology has been extensively used in immunology, hematology, microbiology, and clinical biochemistry [16].
Nanodiagnostics is defined as the use of nanotechnology for state‐of‐the‐art clinical diagnostic purposes to meet the demands of enhanced sensitivity and prognosis of disease in clinical diagnostics. The increased need for accuracy can be met only through a diagnostically significant interaction between analyte molecules and signal‐generating particles to detect a single analyte molecule. Nanotechnology has empowered one‐to‐one interaction between analytes and signal‐generating particles in the size range of proteins (1–20 nm) and other biomolecules [17]. Nanotechnology features matter with dimensions between 1 and 100 nm. This field is playing a substantial role in molecular diagnostics by incorporating new methods based on the inimitable properties of nanometer‐scale materials. They include biobarcodes, dendrimers, nanowires, nanocantilevers, nanopores, and nanofluidic devices [18].
Nanowires are categorized on the basis of metals used—that is, silver nanowires, gold nanowires, and magnetic nanowires. One of the nanowires of great interest is gold nanoparticles‐decorated silicon nanowires (AuNPs@SiNWs). These nanowires are highly efficient near‐infrared (NIR) hyperthermia agents for the destruction of cancerous cells. Three different types of cancerous cells are destructed in 3 mins when these cells are treated with AuNPs@SiNWs by producing efficient heat [19]. CNTs were first reported by Iijima and Ebbese and Ajayan isolated CNTs in large quantities [20]. CNTs are defined as tubular structures with a diameter typically measured in nanometers. The most promising feature of nanotubes is the target delivery of drug toward the tumor [21].
Quantum dots (QDs) are zero‐dimensional semiconductor nanocrystals with very unique properties [22]. Carbon‐based QDs that consist of graphite QDs and carbon QDs were first observed during the purification of single walled carbon nanotubes (SWCNTs) in 2004 and in 2006 from laser ablation of graphite and cement [23]. They are also known as carbon nanolights because of their good solubility and strong luminescence [24]. In the field of biomedicines, it has the potential application in biosensing, drug delivery, and bioimaging because of less toxicity and good biocompatibility [25]. Carbon QDs have low toxicity, and good biocompatibility provides promising features for fluorescent bioimaging ad multimodal bioimaging of cells and tissues. Carbon nanodots are also present in our daily‐life foods such as coffee and breads, proving that they are more biocompatible than the inorganic nanodots. Due to high solubility in water, nontoxicity, excellent biocompatibility, good cell absorbency, multicolor emission, flexibility in surface modification, and high photostability, nanodots are also used as biosensors. Nanorobots, also known as computerized surgical nanorobots or nanobots, can function like a surgeon inside the body under the control of experts [26]. These nanobots are extensions of injectables which go into the body and gather information through images. Properties like chemical sensing; receiving information from, to, and outside the body; locomotion; and computation play very crucial roles in giving output. Picowatts are important for propelling a nanobot at a speed of 1 mm s−1[27].
Nanocantilevers are being introduced in nanorobots. The main significant property of nanocantilevers is real‐time detection. Simply put, they can be used to control objects at the single‐molecule level. Nanocantilevers were fabricated in arrays and selected according to biomolecules. The nanocantilevers vary with the variation in biomolecules. Nano‐based cardiovascular imaging is used for monitoring the live physiological system with high sensitivity and no pain. This live imaging is used for the understanding of pathological conditions and proper diagnosis. The majority of the nano‐based cardiovascular imaging modules include thrombus imaging, theranostic imaging, stem cell imaging, and graft imaging [28].
1.3 Nanopharmaceuticals
The first conceptualization of nanopharmaceuticals could be fairly attributed to Paul Ehrlich when, at the beginning of the twentieth century, he introduced the concept of “magic bullets,” a term used to refer to “ideal therapeutic agents” that act specifically against a particular pathogen without causing damage to host cells. One of the specific applications of nanotechnology has been in the creation of advanced drug‐delivery systems, which have given rise to the term “nanopharmaceuticals.” In order to be classified as a “nanopharmaceutical,” Weissig et al. [29] suggest that the drug product has to meet two major criteria: (i) nanoengineering has to be employed during the manufacturing process, and (ii) the nanomaterial used has to be either essential for the therapeutic activity or has to confer additional and unique properties to the active drug entity.
There are two approaches used in the construction of nanopharmaceuticals: (i) the top‐down approach, consisting of the step‐wise size reduction of large pieces by mechanical or physicochemical methods to create smaller structures, and (ii) the bottom‐up approach, involving the construction of nanometric structures through the self‐assembly of atoms or molecules induced by physical or chemical forces.
During the last decade, the diversification of nanoplatforms has allowed other types of nanopharmaceuticals that are already in clinical trials or approved; we refer here to protein‐based, micelle‐based, and inorganic NPs including pure metals (Au, Ag, etc.) and metal oxides. The majority of nanopharmaceuticals have been employed directly for therapeutic use. The majority of the drugs included among nanopharmaceuticals are pre‐approved drugs; the discovery of novel drugs is not mandatory. Nanoencapsulation solely improves the pharmacokinetic and/or pharmacodynamic characteristics of the drug, increasing the efficacy of the treatments. Nanopharmaceuticals face a series of challenges, including ensuring low toxicity in patients as well as in the environment, the designing of manufacturing methods that represent a good cost–benefit ratio, and, finally, generating a regulatory framework that provides a rapid arrival on the market to products proven to be safe and effective. Nanopharmaceuticals must prove that they can be a revolutionary technological advance to improve the performance of already available or of novel therapeutic agents. Novel applications are now in the pipeline and will soon appear on the market; gene therapy, stimuli–response nanopharmaceutics, and theranostic agents are examples of the next generation of nanodrugs. Liposomes are a submicron and vesicular system for the transport and release of drugs; they are composed of a bilayer or multiple layers with a central aqueous compartment. The development of formulations with liposomes dates from a considerable time back: 1965 [30]. This period has made it possible for these to be one of the drug‐delivery systems possessing a broad impact in the clinic.
Nanopharmaceuticals comprise a new generation of therapeutic‐containing nanomaterials with unique properties and high potential that are capable of solving the constant and ongoing challenge for physicians in proposing novel therapeutic treatments to improve their patients' quality of life.
One of the main advantages of using polymeric nanoparticles (PNPs) with respect to other nanosystems is the possibility of utilizing biocompatible and biodegradable polymers such as poly(alpha‐hydroxy acids), poly(anhydrides), poly(ortho esters), poly(amino acids), etc., avoiding the requirement to remove the residual polymer within the patient's body. PNPs show several advantages in relation to other colloidal systems (e.g. liposomes): (i) better stability in biological fluids and during storage, (ii) easy preparation and diversity in preparation techniques, (iii) reproducibility and easy large‐scale manufacturing, and (iv) batch‐to‐batch reproducibility. Another recent, innovative proposal in nanodrug‐delivery systems comprises polymeric lipid hybrid NPs or lipomers, which are nanocontainers composed of a polymeric core and lipid shell that imparts physicochemical stability and biocompatibility to the NPs. Lipomers have been reported as a blend of the positive attributes of both liposomes and PNPs wherein their individual innate flaws are negated. These lipomers have demonstrated good results as drug‐delivery systems to treat cancer and infectious diseases, as well as for theranostic purposes [31, 32]. The application of nanotechnology in nanopharmaceutical products is an emerging field that provides novel approaches to revolutionizing conventional medical treatments. These nanosystems are designed to modify the properties of drug molecules such as solubility, half‐life, hall biocompatibility, and release characteristics. They can also increase the possibility of crossing the cell membranes and decreasing unwanted adverse effects [33].
Dendrimers offer several mechanisms of interactions with different drugs or biomolecules. The interior is well suited for host‐guest interaction and for the incorporation of hydrophobic/hydrophilic molecules inside their empty cavities (nanoscale containers), which present around the core through hydrophobic interactions and hydrogen bonding. Thus, these can be used as dendritic boxes and unimolecular micelles [34].
In addition, terminal functionalities provide a platform for conjugation by covalent bonding (the prodrug approach) of the drug and targeting moieties. These peripheral functional groups can be employed to tailor‐make the properties of dendrimers, enhancing their versatility. Dendrimers have also been employed to track the drug in specific sited by magnetic resonance imaging (MRI); for instance, Gonawala et al. developed water‐insoluble Combretastatin conjugated to a water‐soluble G3‐succinamic acid Poly(AMidoAMine) (PAMAM) dendrimer, obtaining nanomolecules ranging in size from 3 to 5 nm to monitor cerebral blood flow across the blood‐tumor barrier, observing that the intratumor blood vessels collapsed, leading to necrosis at the core of the tumor [35].
1.4 Role of Nanotechnology in Biological Therapies
Biological therapy is defined as a type of treatment which employs our own organic capabilities (biomolecules) as a source of drugs to treat various diseases. For example, the therapies based on biomolecules for the treatment of infections, cancer, immune system suppression or stimulation, as well as biosystems to directly or indirectly inhibit the proliferation of cancer cells. Biomolecule‐coated CNTs (fullerenes) also release heat under radiofrequency fields [8–10] The thermal properties of nanotubes conjugated to different biomolecules could be useful in the therapy of deep‐tissue tumors, where heat can induce necrosis or apoptosis, since radiofrequency easily penetrates the tissues [36]. AuNPs attach to target‐specific biomolecules (peptides, antibodies, siRNA, aptamers, etc.), which can be luminescent and plasmonic [37].
Their luminescent properties are suitable for acquiring biomedical images, while the photothermal effect in plasmonic AuNPs produces localized heating under irradiation or exposition to laser light or to radiofrequency fields. The combination of polymeric and magnetic nanoparticles (MNPs) functionalized with biomolecules produces smart nanosystems with a response to pH changes, redox fluctuations, or thermal stimuli for drug release, as well as thermal therapy for metastatic cancer, if they are subjected to alternating magnetic fields (AMFs) [38–40]. Therefore, they can be used against tumors by merging hyperthermia with stimuli‐dependent controlled drug delivery [41]. Biological therapies with humanized, chimeric, or human antibodies and in general fusion proteins modulate the immunosystem response to treat diseases [42]. Antibodies and protein fusion have been developed for B or T cell–directed therapies. B cell–directed treatments are based on the depletion and inhibition of costimulation, survival, or differentiation of B cells, while T cell–directed therapies are based on T cell activation [43]. Due to the large variety of NPs, a simple classification is difficult. It is well known that literature lacks a standardized nomenclature [44]. For example, although organic NPs are made from organic matter, the classification excludes carbon‐coated NPs. When designing NPs, size is the most important factor to be considered. For drug delivery, organic NPs are in the size range from 5 to 200 nm and include liposomes, PNPs, dendrimers, micelles, and nanocapsules. Liposomes, lipid‐based NPs, and PNPs are the most studied nanosystems [45–47].
PNPs are submicron‐sized colloidal particles, formed by biodegradable or nondegradable polymers [48, 49]. This type of nanoparticle has promising properties that make it useful as a delivery vehicle. The encapsulation is relatively easy, with high capacity and low toxicity [50]. It is well known that encapsulation of hydrophobic drugs improves their bioavailability and tolerability. Also, PNPs are functionalized with specific ligands to make them able to reach a specific receptor site, thus improving the tumor‐targeting properties with practically no toxic effects. The main properties of polymeric nanosystems are biocompatibility, biodegradability, and the advantage to encapsulate a great number of therapeutic drugs (alone or combined). Exosomes are a bilayer membrane containing several types of phospholipids and proteins that are involved in several biological and pathological processes. They provide specialized cell‐to‐cell communications useful for drug delivery systems in targeting cells. Exosomes originate from endosomes and have a size between 40 and 100 nm. An exhaustive investigation has been carried out to use exosomes as drug delivery approaches [51, 52]. Therapeutic applications of functionalized AuNPs are widely used because of their multifunctional properties as well as their simple synthesis, controllable size, strength dispersity, easy ligand exchange, biocompatibility, and absence of toxicity. Due to the “gentle” chemical nature of gold, functionalization with target‐specific ligands is relatively easy, mainly via gold‐thiolate bonding.
QDs are inorganic nanomaterials (e.g. CdSe, CdS, CdTe/CdS, ZnS, PbS, and InP) with optical properties for different bioapplications due to their emissions in the NIR region. Although QDs have been widely used for diagnosis, therapeutic and theranostic alternatives are possible. The conjugation of QDs to biomolecules such as antibodies has also been explored for biocompatible systems such as anti‐VEGFR2‐QD655 (QDs with emission at 655 nm) [53], bevacizumab‐QD [54] and Anti‐HER2‐QD [55]. In addition to conventional targeting and delivery, QDs have also been used to deliver peptides and proteins (cell‐penetrating peptide and His6‐tagged beta‐D‐galactosidase: JB577‐Qds‐GALC) [56], nucleic acids (siRNA) [57], drugs, polymers [58], polysaccharides [59], etc. Conventional NPs are used for the transport of biomolecules such as proteins and drugs based on nucleic acids [60–68], interleukines [69–71], monoclonal antibodies [72–74], enzymes [75, 76], peptides [77, 78] and substances of natural origin [78–80]. The in vivo stability of these biological substances—in particular, proteins (of easy renal clearance and enzymatic degradation)—is significantly improved by being protected by the nanoparticle [81]. Cellular internalization is vital for the therapy to be effective. The primary role is played by the cell membrane [82, 83], although the size, shape, load, and stiffness of the nanoparticle also play a significant role. The main mechanism of internalization of nanoparticle‐based drug delivery systems (NDDS) is endocytosis (phagocytosis and pinocytosis); particles larger than 500 nm are internalized by phagocytosis, while smaller ones are internalized by pinocytosis (caltrin‐independent or not) that may or not be mediated by receptors [84].
The type of endocytosis determines the degree of internalization. In caltrin‐mediated endocytosis, the particle reaches the lysosomal compartment, but if mediated by caveolin, the particle does not reach the compartment. When the surface of the NPs is functionalized with ligands for targeted therapy, the fundamental mechanism of internalization is receptor‐mediated endocytosis [85]. The changes that occur as the NPs penetrate the tumor tissue influence the release. Tumor tissue is characterized by low oxygen levels and low perfusion, which cause hypoxia. The pH is more acidic as a result of the production of carbon dioxide and lactic acid [86]; this difference in pH causes variation in the concentrations of several enzymes that contribute to particle degradation and drug release [87].
1.5 Nanomaterials for Gene Therapy
Nanotechnology has found increased applications in biomedical therapies due to their nanosize and the ability to mimic the native molecules of the biological system of the human body. Current understanding of the potential toxicity of nanomaterials is very limited because of their extremely small size. They could be retained longer within the biological system. Not only in therapies but also in day‐to‐day applications, nanotechnology could lead to exposure to NPs, which can get accumulated in the biological system by ingestion, inhalation, and penetration. In vivo studies on rodents and humans [88] focused on the clearance of nanomaterials from organs of the human body after exposure by inhalation. From this study it was evident that lungs (as the port for entry of the nanomaterial), the liver, and kidneys are the major organs affected by nanomaterials. If the nanomaterial enters the human body via ingestion or inhalation, they can cause tissue injury by accumulating in tissue. But mostly, when they enter the bloodstream, they can be translocated to different parts of the body via blood circulation [89]. In the case of lungs, airway and alveolar macrophages are the first line of defense against nanomaterials. But it was observed in case studies that any nanomaterial aggregates less than 100 nm were not cleared by phagocytosis [90, 91].
