Nanoparticles for Therapeutic Applications

Madhuri Sharon, (Retd Director at Reliance Industries), PhD from Leicester University, UK, postdoctoral research from Bolton Institute of Technology U.K., is currently the Director of NSN Research Centre for Nanotechnology & Bionanotechnology and Managing Director of Monad Nanotech as well as Adjunct-Professor University of Mumbai & Professor-Emeritus JJT University, India. She has published more than 130 papers, six books, and 11 patents. Her research focuses on the synthesis, biosynthesis, and application of various nanomaterials (graphene oxide, carbon dots, carbon nanomaterials, and nanometals) in drug delivery.

• Foreword xxiPreface xxiiiPart I: Nano-Flotillas Traversing in the Vein as Carriers to Deliver Theranostics 11 Diagnostic and Therapeutic Systems Using Nanomaterials 31.1 Introduction 31.2 Nanodiagnostic Agents 41.2.1 Bio-Barcode Assay (BCA) 51.2.2 Cantilever Beam 51.2.3 Carbon Dots/Carbon Quantum Dots 81.2.3.1 CD as Bioimaging Agent 91.2.3.2 CD as Sensor 101.2.4 Carbon Nanotubes (CNTs) 111.2.4.1 Diagnostic Equipment Using CNT 131.2.5 Dendrimers 261.2.5.1 Types of Dendrimers 271.2.5.2 Applications of Dendrimers 281.2.6 DNA 301.2.7 Nanocrystals/Quantum Dots (QDs) 331.2.7.1 Applications of Nanocrystals/Quantum Dots (QDs) 341.2.8 Nanoparticles as Diagnostic Tool 351.2.8.1 Inorganic/Metal Nanoparticles 351.2.8.2 Polymeric Nanoparticles (PNPs) 431.2.9 Nanorobotics 451.2.10 Nanoshells 471.2.11 Nanowires 481.2.12 Optical Tweezers 481.2.13 Serum Albumin 501.3 Summary 51References 512 Nano Trojan Horses for Delivery of Peptides and Protein Drugs 57Roopa Dharmatti2.1 Introduction 572.2 Peptides 582.2.1 Cell-Penetrating Peptides 612.2.1.1 CPP and NP Surface Conjugation Mechanism 622.2.1.2 CPP-NP Conjugates in Cancer 642.2.1.3 CPP-NP Conjugates in Inflammation 652.2.1.4 CPP-NPs Conjugates in Central Nervous System Disorders 662.2.2 Antimicrobial Peptides (AMPs) 662.2.2.1 Nanomedicines for Antimicrobial Peptides Delivery 682.2.3 Peptide Toxins 702.2.3.1 Action Mechanism of Peptide Toxins 712.2.3.2 Therapeutic Applications of Peptide Toxins from Various Sources 712.2.4 Modifications of Natural Peptides for NP and Drug Design 772.3 Role of Nanoparticles in Peptide Drug Delivery 772.3.1 Vasoactive Intestinal Peptide (VIP) NPs for Diagnostics and for Controlled and Targeted Drug Delivery 792.3.1.1 NPs for VIP Drug Delivery 802.3.1.2 Structural Basis for Neuropeptide VIP-Targeted Drug Delivery Aided by Nanotechnology 822.4 Protein 852.4.1 Protein and Peptide Drug Conjugates 862.4.1.1 Protein-Drug Conjugates 862.4.1.2 Strategies for Chemical Conjugation 902.5 Role of Nanoparticles (NPs) in Protein Drug Delivery 962.5.1 Liposomes 962.5.2 Nanoparticles (NPs) Made from Polymer 972.5.3 Carbon Nanotubes (CNTs) 992.5.4 Other Metal Nanoparticles (NPs) 1002.6 Summary 102References 1023 Biomimetic Nanomaterials as Smart Scaffolds for Tissue Regeneration 1153.1 Introduction 1153.1.1 Concept of Tissue Engineering (TE) 1163.1.2 A Brief Look at the Type of Tissue-Specific Stem Cells Being Engineered for Tissue Regeneration 1173.1.3 Growth Factor 1193.2 Scaffold 1193.2.1 Basic Requirements for Scaffold 1203.2.1.1 Biocompatibility of Scaffold Material 1203.2.1.2 Biodegradability of Scaffold Material 1213.2.1.3 Mechanical Properties of Scaffold Material 1213.2.1.4 Porosity in Scaffold Architecture 1213.2.1.5 Surface Chemistry of Scaffold 1213.2.2 Biological Scaffold Fabrication Techniques 1223.2.2.1 Conventional Fabrication Techniques 1223.2.2.2 Rapid Prototyping (RP) Technique or Solid Free-From Fabrication Technique 1253.2.2.3 Decellularization 1283.2.2.4 Tissue Vascularization and Integration 1293.2.2.5 3D Bioprinting or Cell Printing 1293.2.2.6 Crosslinking of Hydrogel 1323.3 Biomaterials for the Fabrication of Scaffold 1323.3.1 Natural Biomaterials and Extracellular Matrix Material (ECM) Used for Scaffolding 1323.3.1.1 Collagen 1333.3.1.2 Fibrin 1343.3.1.3 Gelatin 1363.3.1.4 Silk Fiber 1373.3.1.5 Proteoglycan (PG) 1373.3.1.6 Hyaluronan or Hyaluronic Acid (HA) 1383.3.1.7 Chitosan 1383.3.1.8 Alginate 1393.3.1.9 Silica 1403.3.1.10 Poly(Ethylene Glycol) (PEG) 1403.3.2 Synthetic Biodegradable Polymer Biomaterials Used for Scaffolding 1413.3.2.1 Poly(L-lactic Acid) (PLA) Scaffold 1423.3.2.2 Polyglycolide (PGA) Scaffold 1423.3.2.3 Poly(Lactic-co-Glycolic Acid) (PLGA) Scaffold 1423.3.2.4 Polycaprolactone (PCL) Scaffold 1433.3.2.5 Hydrogel 1433.3.3 Ceramics 1433.3.4 Functionality of Types of Scaffolds 1443.3.4.1 Injectable Material for Scaffolds or ‘Injectabone’ 1443.3.4.2 Scaffold as Delivery System for Growth Factor and Drugs 1443.3.4.3 Supercritical Carbon Dioxide Processing of Polymers 1453.3.4.4 Customized Scaffold via 3D Printing 1453.3.4.5 Plasma Modification of Scaffold Surfaces 1463.4 Nanomaterials for Versatile Scaffolds 1463.4.1 Carbon-Based Nanoparticle Carbon Nanotubes as Versatile Scaffolds 1483.4.2 Metal Nanoparticles 1523.4.2.1 Tantalum (Ta) 1533.4.2.2 Magnesium and Its Alloys 1533.4.2.3 Titanium and Its Alloys 1543.4.2.4 Silver Nanoparticles (AgNPs) 1543.4.2.5 Aluminum Nanoparticles (AlNPs) 1553.4.2.6 Gold Nanoparticles (AuNPs) 1563.4.2.7 Copper Nanoparticles (CuNPs) 1573.4.2.8 Iron (Fe), Iron Oxide and Its Conjugate Nanoparticles 1583.4.2.9 Nickel Nanoparticles (NiNPs) 1593.4.2.10 Zirconium Nanoparticles (ZrNPs) 1603.4.3 Polymeric Nanoparticles and Nanofibers 1603.4.4 Lipid-Based Nanoparticles 1613.4.4.1 Liposomes 1623.4.5 Ceramic Nanoparticles (CNPs) 1633.4.5.1 Bioactive Ceramic Nanoparticles 1643.4.5.2 Bioinert Ceramic Nanoparticles 1643.4.5.3 Bioresorbable Ceramic Nanoparticles 1643.4.6 Natural Extracellular Matrix (ECM) 1653.5 Application of Scaffold for Various Tissue Regeneration and Incorporation of Nanomaterials 1653.5.1 Scaffold for Bone Tissue Regeneration 1663.5.2 Scaffold for Cartilage Tissue Regeneration 1703.5.3 Scaffold for Cardiovascular Tissue Regeneration 1723.5.4 Scaffold for Liver Tissue Regeneration 1733.5.5 Scaffold for Muscle Tissues Regeneration 1753.5.6 Scaffold for Nerve Tissue Regeneration 1763.5.7 Scaffold for Skin Tissue Regeneration 1803.5.8 Scaffold for Tendon and Ligament Tissue Regeneration 1833.6 Considerations for Manufacturing a Scaffold at Commercial Level 1863.7 Conclusion 187References 187Part II: The Cardinal Role of Biomedical Nanotechnology 2094 Nanodiagnostics and Nanotherapeutics: A Powerful Tool for Ablation of Cancer 2114.1 Introduction 2114.2 Molecular Diagnostics 2124.2.1 Radioimmunoassay (RIA) 2154.2.2 Enzyme-Linked Immunosorbent Assay (ELISA) 2154.2.3 SDS-Page and Western Blot 2164.2.4 Immunoprecipitation (IP) 2174.2.5 Immunofluorescence 2184.2.6 Immunoelectron Microscopy 2184.2.7 Polymerase Chain Reaction (PCR) 2184.3 Radiological Diagnostics for Cancer 2194.3.1 Computerized Tomography (CT) Scan 2194.3.2 Magnetic Resonance Imaging (MRI) 2194.3.3 Positron Emission Tomography (PET) 2204.4 Biopsy 2224.5 Nanodiagnostics for Cancer 2234.5.1 Brain Cancer 2244.5.1.1 Brain Cancer and Nanotechnology 2264.5.2 Breast Cancer 2284.5.2.1 Breast Cancer and Nanodiagnostic 2304.5.3 Colon/Colorectal Cancer 2304.5.3.1 Colon/Colorectal Cancer and Nanodiagnostic 2314.5.4 Liver Cancer or Hepatocellular Carcinoma (HCC) 2334.5.4.1 Liver Cancer and Nanotechnology 2344.5.5 Lung Cancer 2394.5.5.1 Lung Cancer and Nanotechnology 2404.5.6 Melanoma and Skin Cancer 2424.5.6.1 Melanoma and Nanotechnology 2444.5.7 Oral Cancer 2464.5.7.1 Oral Cancer and Nanotechnology 2474.5.8 Ovarian Cancer 2484.5.8.1 Ovarian Cancer and Nanotechnology 2494.5.9 Pancreatic Cancer 2514.5.9.1 Pancreatic Cancer and Nanotechnology 2524.5.10 Prostate Cancer 2554.5.10.1 Prostate Cancer and Nanotechnology 2574.5.11 Renal Cancer/Kidney Cancer 2594.5.11.1 Renal Cancer and Nanotechnology 2614.5.12 Urinary Bladder Cancer 2614.5.12.1 Urinary Bladder Cancer and Nanotechnology 2624.6 Summary 264References 2655 Genetic Diseases and Nanotechnology-Based Theranostics 2775.1 Introduction 2775.2 Nanotechnologies and Microchips in Genetic Diseases 2795.3 Nanotechnology and Gene Therapy for Genetic Disease 2795.3.1 Diabetic Retinopathy (DR) 2815.3.2 Some Diseases Successfully Treated with Nanotechnology + Gene Therapy 2825.4 Gene Silencing Therapy 2845.5 Ribonucleic Acid (RNA) Therapy and Nanotechnology 2865.6 Nanoparticles-Based Therapies for Various Chromosomal Disorders 2875.6.1 Down Syndrome 2875.6.1.1 Mosaic Down Syndrome 2875.6.1.2 Translocation Down Syndrome 2885.6.1.3 Klinefelter Syndrome (47,XXY) 2885.6.1.4 Turner Syndrome 2885.6.1.5 Williams Syndrome 2885.6.1.6 Cri du Chat Syndrome 2895.6.2 Single-Gene Disorder 2895.6.2.1 Niemann-Pick Type C1 Disease (NPC1) 2895.6.2.2 Cystic Fibrosis 2905.6.2.3 Galactosemia 2915.6.2.4 Severe Combined Immunodeficiency (SCID) 2925.6.2.5 Sickle Cell Disease (SCD) 2925.6.2.6 Huntington’s Disease (HD) 2935.6.2.7 Tay-Sachs Disease 2945.6.3 Multifactorial Disorders 2955.6.3.1 Thalassemia 2955.6.3.2 Mitochondrial Disease 2965.7 Summary 299References 2996 The Role of Biomedical Nanotechnology in CNS and Neurological Disorders 3036.1 Introduction 3036.2 Parkinson’s Disease 3046.2.1 Nanotheranostic for Parkinson’s Disease (PD) 3066.3 Alzheimer’s Disease 3096.3.1 Nanotheranostic for Alzheimer’s Disease 3126.4 Epilepsy/Seizure Disorder 3166.4.1 Nanotheranostic for Epilepsy 3186.5 Schizophrenia 3196.5.1 Nanotheranostic for Schizophrenia 3206.6 Summary 323References 3247 Nanotechnology-Based Theranostics for Fighting Infectious Diseases 3297.1 Introduction 3297.2 Diseases Caused by Prions 3337.2.1 Nanotheranostic for Diseases Caused by Prions 3347.3 Diseases Caused by Virus 3367.3.1 HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome) and Nanotheranostic 3397.3.2 Hepatitis C Virus and Nanotheranostic 3417.3.3 Dengue Virus and Nanotheranostic 3447.3.4 Polio Virus and Nanotheranostic 3477.3.5 Meningitis-Causing Virus and Nanotheranostic 3497.3.6 Herpes-Causing Virus and Nanotheranostic 3517.3.7 Influenza (Flu)-Causing Virus and Nanotheranostic 3547.3.8 COVID-19 (Coronavirus) Nanotheranostic 3577.4 Diseases Caused by Bacteria 3627.4.1 Nanotheranostics for Diseases Caused by Bacteria 3767.4.1.1 Antibacterial Nanoparticles, Nanoantibiotics and Nanotechnology 3767.4.1.2 Nano-Strategies to Fight Multidrug-Resistant (MDR) Bacteria 3767.4.1.3 Theranostics to Combat Biofilms of Bacteria 3797.4.1.4 Theranostics for Bloodstream Infection 3817.4.1.5 Nanoparticles for Drug Delivery 3817.4.1.6 Modulation of Immune Response by Nanoparticles for Efficient Vaccination 3827.5 Diseases Caused by Fungi 3827.5.1 Nanotheranostic for Diseases Caused by Fungi 3857.5.1.1 Nanotechnology for Cutaneous Fungal Infection Therapy 3857.5.1.2 Nanotechnology for Invasive Mycoses Therapy 3867.5.1.3 Nanotechnology for Ocular Mycoses Therapy 3887.6 Diseases Caused by Parasitic Protozoa 3897.6.1 Nanotheranostics for Diseases Caused by Parasitic Protozoa 3937.6.1.1 Leishmaniasis, Chagas Disease and African Trypanosomiasis 3947.6.1.2 Malaria 3957.6.1.3 Amebiasis 3967.6.1.4 Giardiasis 3967.7 Diseases Caused by Helminths 3977.7.1 Nanotheranostic for Diseases Caused by Parasitic Helminths 3997.7.1.1 Nanotherapeutics and Nematodes (Roundworms) 3997.7.1.2 Nanotherapeutics and Trematodes (Flatworms) 4017.7.1.3 Nanotherapeutics and Cestodes (Tapeworms) 4027.8 Summary 403References 4038 Nanotheranostics for Cardiovascular Diseases 4198.1 Introduction 4198.1.1 The Human Heart 4198.1.2 Blood Vessels 4198.1.3 Heart or Cardiovascular Diseases 4218.1.4 Diseases of the Blood Vessels 4238.1.5 Diagnostics and Therapeutics of Cardiovascular Disease 4258.2 Nanotheranostics for Cardiovascular Diseases 4268.2.1 Nanodiagnostics for Cardiovascular Disease 4278.2.2 Nanotherapeutics for Cardiovascular Disease 4298.2.2.1 Liposome NP for Cardiovascular Therapy 4308.2.2.2 Polymeric Nanoparticles for Cardiovascular Therapy 4318.2.2.3 Micelle NP for Cardiovascular Therapy 4328.2.2.4 Dendrimers for Cardiovascular Therapy 4348.2.2.5 Gel Nanoparticles for Cardiovascular Therapy 4358.2.2.6 Metal Nanoparticles for Cardiovascular Therapy 4358.2.2.7 Nanocoated Stents for Coronary Artery Bypass Graft (CABG), Percutaneous Transluminal Coronary Angioplasty (PTCA) and Percutaneous Coronary Intervention (PCI) 4368.2.2.8 Nano Patch and Scaffold for Cardiovascular Disease 4368.2.2.9 Suitability of Carbon Nanotubes for Cardiovascular Therapy 4388.3 Summary 439References 4409 Role of Nanotechnology in Combatting Disease and Disorders of Ophthalmology 4459.1 Introduction 4459.2 Structure and Anatomy of the Human Eye 4459.3 Eye Diseases and Disorders 4499.3.1 Diseases and Disorders of Accessory Structures 4499.3.1.1 Dry Eye 4499.3.1.2 Conjunctivitis 4509.3.1.3 Blepharitis/Blepharoptosis (Ptosis) 4509.3.1.4 Hordeolum (Stye) 4509.3.1.5 Chalazion (Meibomian Cyst) 4519.3.1.6 Entropion 4519.3.1.7 Ectropion 4519.3.2 Diseases and Disorders of Fibrous Tunic 4519.3.2.1 Keratoconus 4519.3.2.2 Refractive Errors 4529.3.3 Diseases and Disorders of Vascular Tunic 4539.3.3.1 Uveitis 4539.3.4 Diseases and Disorders of Nervous Tunic 4549.3.4.1 Color Blindness 4549.3.4.2 Retinal Detachment 4549.3.4.3 Diabetic Retinopathy (DR) 4569.3.4.4 Age-Related Macular Degeneration (AMD) 4579.3.5 Diseases and Disorders of Interior Eyeball 4579.3.5.1 Glaucoma 4579.3.5.2 Cataract 4599.3.5.3 Floater 4619.3.6 Diseases and Disorders of Cornea and Uveal Tract 4619.3.6.1 Pterygium 4619.3.6.2 Keratitis 4629.3.6.3 Scleritis 4629.3.6.4 Iritis 4639.3.7 Muscular Disorders 4639.3.7.1 Nystagmus 4639.3.7.2 Strabismus (Crossed Eyes) 4639.4 Blindness 4639.4.1 Trachoma 4649.5 Nanotherapy for Ocular Diseases and Disorders 4649.5.1 Nanotechnology for Regenerative Ophthalmology 4659.5.1.1 Nanoscaffolds for Retinal Tissue Regeneration 4669.5.1.2 Nanoscaffolds for Corneal Tissue Regeneration 4689.5.2 Nanomaterials as Gene Delivery Devices to Reprogram Cells for Ocular Regeneration 4709.5.2.1 Lipoplexes: Liposome-Protamine-DNA (LPD) Nanocomplexes 4719.5.2.2 Polyplexes 4719.5.2.3 Mesoporous Nanoparticles 4729.5.2.4 Organic-Inorganic Hybrid Nanocrystals 4729.5.2.5 NanoScript Nanoparticle 4729.5.2.6 Self-Assembling DNA and Magnetic Nanoparticles 4739.5.3 Nanomaterials as Immunomodulator in Ocular Regeneration 4739.6 Glaucoma: Potential Implications of Nanotechnology and Nanomedicine 4759.6.1 Drug Delivery System for Arresting Glaucoma 4759.7 Cataract: Potential Implications of Nanotechnology and Nanomedicine 4809.7.1 Nanoscaffolds for Lens Regeneration (Cataract) 4809.7.2 Nanofiber-Based Hydrogel 4819.8 Uveitis (Eye Inflammation) Therapy by Nanozyme (Superoxide Dismutase 1) 4829.9 Contact Lenses for Ocular Theranostic 4829.10 Nanodiagnostic for Ocular Diseases and Disorders 4839.11 Summary and Future Perspective 484References 48510 Use of Nanotechnology in Dentistry 49310.1 Introduction 49310.1.1 Structure of Human Teeth 49310.1.2 Types of Human Teeth 49410.2 Diseases and Disorders of Teeth 49510.2.1 Plaque Formation 49510.2.2 Caries (Cavities) 49610.2.3 Periodontal Disease 49610.2.3.1 Periodontitis 49710.2.3.2 Gingivitis 49710.2.4 Trench Mouth 49710.2.5 Thrush 49710.2.6 Periapical Abscess (Dentoalveolar Abscess) 49810.2.7 Malocclusion 49810.2.8 Dry Mouth 49810.2.9 Herpetic Gingivostomatitis 49810.2.10 Mumps 49910.2.11 Mouth Ulcer 49910.2.12 Stained Teeth 50010.2.13 Hyperdontia (Extra Teeth) 50010.3 Nanotheranostics Used in Dentistry 50010.3.1 Nanotechnology for Diagnosis 50110.3.1.1 Nanocantilevers for Diagnostics 50310.3.1.2 Nanopores/Porous Nanoparticles for Diagnostics 50310.3.1.3 Nanotubes for Diagnostics 50310.3.1.4 Quantum Dots (QD) for Diagnostics 50310.3.1.5 Nanoelectromechanical Systems (NEMS) for Diagnostics 50410.3.1.6 Lab-on-a-Chip or Biochips and Salivary Biomarkers for Diagnostics 50410.3.1.7 Oral Fluid Nanosensor Test (OFNASET) for Diagnostics 50510.3.1.8 Nanorobots or Dentifrobots for Diagnostics 50610.3.1.9 Digital Dental Imaging for Diagnostics 50710.3.2 Nanomaterials Used in Dental Therapeutics 50710.3.2.1 Organic Nanomaterials for Therapeutics 50710.3.2.2 Inorganic Nanomaterials for Therapeutics 50810.3.2.3 Nanocomposites for Therapeutics 50910.3.2.4 Carbon-Based Nanomaterials for Therapeutics 51110.3.2.5 Nonsolution (Nano Adhesive) for Therapeutics 51110.3.2.6 Nano Light-Curing Glass Ionomer Restorative 51110.3.2.7 Nanoneedles 51210.3.3 Role of Nanotechnology in Dental Tissue Engineering 51210.3.3.1 Nanotechnology in Bone Grafting/Regeneration and Oral Maxillofacial Surgery 51410.3.3.2 Nanotechnology for Dental Pulp Regeneration 51410.3.3.3 Nanostructures and Enamel Tissues Engineering/Restoration 51510.3.3.4 Nanotechnology and Nerve Regeneration 51510.3.4 Bio-Nanofunctionalized Surface of Dental Implants 51710.3.4.1 Prosthodontics and Nanotechnology 51810.3.5 Nanomaterials for Periodontal Drug Delivery 52010.3.6 Endodontics 52210.3.7 Nanoanesthesia 52410.3.8 Nanotechnology and Dental Disease Prevention 52410.3.8.1 Nano Toothbrush 52510.3.8.2 Nano-Modified Toothpaste and Mouthwash 52510.3.8.3 Nanomaterials for Prevention of Caries 52610.3.8.4 Nanomaterials for Prevention of Periodontal Disease 53010.3.9 Antimicrobial Photodynamic Therapy (APDT) 53110.4 Conclusion 534References 535Index 545