Nanomedicine (eBook)

Preface 6
Contents 10
Chapter 1: Nanomedicine: Revolutionary Interdiscipline 12
1.1 Introduction 12
1.2 Enhancement of Existing Technology: The Top-Down Revolution 13
1.3 From the Bottom-Up, Introduction of New Technology and the True Revolution 14
1.4 Interdisciplinary Medicine, Why the Fuss? 14
1.5 Technologies of Nanomedicine 15
1.5.1 Nanobiotechnology 16
1.5.2 Nanotechnology 17
1.5.3 The Revolution of Interdiscipline 18
1.5.4 Nanobiomimetics 19
1.6 Conclusions and Future Outlook 20
References 21
Chapter 2: Nanobiology in Medicine 25
2.1 Introduction to Nanobiology 25
2.2 Nanobiology and Human Biology 27
2.3 Nanomaterials for Medicine 29
2.4 Nanobiology: Applications in Medicine 32
2.4.1 Diagnostic Applications of Nanoparticles 32
2.4.2 Therapeutic Applications of Nanoparticles 34
2.5 Conclusions and Future Outlook 37
References 38
Chapter 3: Tissue Engineering In Vivo with Nanotechnology 42
3.1 In vivo Nanotechnology Tissue Engineering Studies 42
3.1.1 Bone Studies 43
3.1.1.1 Nanomaterial-Coating 43
3.1.1.2 Injectable Nanomaterials 44
3.1.1.3 Nanofiber Materials 44
3.1.1.4 Nanocomposite Materials 45
3.1.2 Neural Studies 46
3.1.2.1 Nanofiber Materials 47
3.1.2.1.1 Self-assembling Nanofibers 47
3.1.2.1.2 Electrospun Nanofibers 47
3.1.2.1.3 Carbon Based Nanofibers 48
3.1.3 Wound Repair Studies 49
3.1.3.1 Nanocomposites 50
3.1.3.2 Nanofiber Materials 51
3.1.3.3 Nanoparticles 52
3.1.4 Other Tissue Engineering Applications 53
3.1.4.1 Vascular System 53
3.1.4.2 Cardiac System 53
3.1.4.3 Visual System 54
3.2 Nanotechnology for Improved In Vivo Antimicrobial Response 54
3.2.1 Wound Repair 55
3.2.1.1 Antimicrobial Nanofeatured Biomaterials 55
3.2.1.2 Antimicrobial Nanoparticles Improve Wound Repair 57
3.2.1.3 Biomaterials Coupled with Antimicrobial Nanoparticles 57
3.2.2 Bone Defect and Fracture Repair 58
3.2.3 Other Tissue Engineering Applications 62
3.2.3.1 Gastrointestinal Tissue Repair 62
3.2.3.2 Abdominal Tissue Repair 62
3.3 Immune Response to Nanomaterials 64
3.3.1 Inflammation Pathway 64
3.3.1.1 Foreign Body Response Summery 64
3.3.1.2 Inflammation in the Central Nervous System 65
3.3.1.3 Injectable Scaffolds 65
3.3.1.4 Different Inflammation Cascades 66
3.3.2 Future of Nanomaterials Inflammation 66
3.4 Conclusions and Future Perspectives 66
References 67
Chapter 4: Nanomaterial Design and Computational Modeling 72
4.1 Introduction 72
4.2 First-Principles Methods 74
4.2.1 Born-Oppenheimer Approximation 74
4.2.2 Density Functional Theory 75
4.2.3 Self-Consistent Field Processes in DFT 77
4.2.4 Examples 77
4.3 Tight Binding 78
4.3.1 Linear Combination of Atomic Orbitals 79
4.3.2 Slater-Koster Two-Center Approximation 80
4.3.3 Total Energy in TB 83
4.3.4 Examples 83
4.4 Molecular Dynamics 84
4.4.1 Empirical Potentials 85
4.4.1.1 Lennard-Jones Potential 85
4.4.1.2 Embedded Atomic Method 85
4.4.2 Integrator of Motion Equations 86
4.4.2.1 Verlet algorithm and Prediction-Correction Algorithm 86
4.4.3 Examples 87
4.5 Conclusions and Future Outlook 89
References 90
Chapter 5: Medical Nanomaterials 92
5.1 Introduction 92
5.2 The Need for New Medical Technologies 93
5.3 The Advantage of Nanotechnology 94
5.4 The Market for Medical Nanotechnologies 97
5.5 Medical Nanomaterials 98
5.5.1 A Systematic Approach to Understanding Nanomaterials 98
5.5.2 An In-Depth Look at Various Nanomaterials 100
5.5.2.1 From Liposomes to Polymer Nanoparticles for Drug Delivery 100
5.5.2.2 Gold Nanoparticles as Diagnostic Agents and Therapeutic Vehicles 101
5.5.2.2.1 Synthesis Methods 101
5.5.2.2.2 Diagnostic Applications 102
5.5.2.2.3 Therapeutic Applications 103
5.5.2.3 Multi-component Nano-devices 103
5.6 Summary and Future Outlook 105
References 105
Chapter 6: Multifunctional Nanoparticles for Theranostics and Imaging 109
6.1 Introduction 110
6.2 Design of Multifunctional Nanoparticle for Therapeutics and Diagnostics 110
6.3 Designs of Multifunctional Nanoparticle for Medical Imaging 113
6.3.1 Accumulation and Absorbance 113
6.3.2 Distribution 113
6.3.3 Metabolism and Drug Release 115
6.3.4 Excretion and Clearance 117
6.4 Conclusions 119
6.5 Future Perspective 119
References 120
Chapter 7: Medical Nanobiosensors 124
7.1 Introduction 125
7.2 Biorecognition Probes 126
7.2.1 Antibodies 127
7.2.2 Aptamers 128
7.2.3 Enzymes 128
7.2.4 Nucleic Acids 128
7.3 Transduction Modes 128
7.3.1 Optical Detection 128
7.3.2 Electrochemical Detection 129
7.3.3 Electrical Detection 129
7.3.4 Mass Sensitive Detection 129
7.3.5 Thermal Detection 129
7.4 Nanomaterials: The Nanobiosensors Toolbox 129
7.4.1 Zero-dimensional Nanomaterials 130
7.4.1.1 Quantum Dots (QDs) 130
7.4.1.1.1 Gold Nanoparticles (AuNPs) 130
7.4.1.1.2 Magnetic Nanoparticles (MNPs) 130
7.4.2 One-Dimensional Nanomaterials 130
7.4.2.1 Carbon Nanotubes (CNTs) 130
7.4.2.2 Nanowires 131
7.4.3 The Innovative Two-Dimensional Material: Graphene 131
7.5 Nanobiosensing Strategies Toward Medical Applications in Health Priorities: Biomarkers Detection 131
7.5.1 Neurodegenerative Diseases 138
7.5.2 Cardiovascular Diseases 140
7.5.3 Cancer 142
7.6 Conclusions and Future Perspectives 144
References 145
Chapter 8: Nanotechnology in Advanced Medical Devices 151
8.1 Introduction 152
8.1.1 Nanoimaging 155
8.1.1.1 Quantum Dots 155
8.1.1.2 Magnetic Resonance Imaging 156
8.1.1.3 Atomic Force Microscopy 157
8.1.1.4 Optical Tweezers 159
8.1.2 Nanobiosensors 159
8.1.2.1 Electrochemical Biosensors 160
8.1.2.2 Optical Biosensors 160
8.1.2.3 Piezoelectric Biosensors 162
8.1.2.4 Nanotechnological Impact 162
8.1.2.5 Progress to Lab On a Chip (LOC) 163
8.1.3 Surgery and Clinical Applications 164
8.1.3.1 Nanosurgery 165
8.1.3.2 Implantable Devices 166
8.1.3.3 Tissue Regeneration and Prosthetics 167
8.1.4 Hindrances and Effects to be Considered 168
8.1.4.1 Scientific Hindrances 169
8.1.4.2 Regulatory Hindrances 169
8.2 Summary and Outlook 170
References 172
Chapter 9: Wireless Actuation of Micro/Nanorobots for Medical Applications 176
9.1 Introduction 176
9.2 Magnetic Actuation 177
9.2.1 Gradient Field for Concentration and Steering of Magnetic Therapeutic Carriers 178
9.2.1.1 Concentrating Magnetic Carriers at Targeted Sites by External Magnets 178
9.2.1.2 Concentrating Magnetic Therapeutic Carriers Directly at Implants 178
9.2.1.3 Steering Magnetic Therapeutic Carriers in Flows by MRI Systems 181
9.2.2 Magnetic-Torque-Driven Propulsion at Low Reynolds Number 181
9.2.3 Scaling Effects of Micro/Nanorobots Driven by Magnetic Force and Torque 184
9.3 Bacterial Actuation 185
9.4 Chemical-Fuel-Driven Actuation 186
9.4.1 Principle and Fabrication 187
9.4.2 Applications 187
9.5 Wirelessly-Actuated Robotic Tools 189
9.6 Conclusions and Future Outlook 191
References 191
Chapter 10: Pharmaceutical Nanotechnology: Overcoming Drug Delivery Challenges in Contemporary Medicine 195
10.1 Challenges in Delivery of Contemporary Therapeutics 195
10.1.1 Chemical Challenges 196
10.1.2 Remote Disease Targets 198
10.2 Nanotechnology Solutions 200
10.2.1 Enhancing Solubility and Permeability 200
10.2.2 Targeted Delivery to Disease Sites 201
10.2.3 Intracellular and Subcellular Delivery 203
10.2.4 Enabling Non-invasive Delivery 203
10.3 Illustrative Examples of Nanotechnology Products 204
10.3.1 Lipid-Based Nanosystems 206
10.3.2 Polymer-Based Nanosystems 208
10.3.3 Nano-sized Drug Crystals 210
10.4 Multifunctional Nanotechnology 211
10.4.1 Choice of Materials for Nanotechnology 211
10.4.2 Surface Modification to Increase Availability at Tissue and Cell Levels 216
10.4.3 Image-Guided Therapy 217
10.4.4 Combination Therapeutics 218
10.5 Regulatory Issues in Nano-pharmaceuticals 219
10.5.1 Approval of Pharmaceutical Products in the US 219
10.5.2 Preclinical and Clinical Development 223
10.5.3 Knowledge Management, Manufacturing and Scale-Up 224
10.6 Conclusions and Future Outlook 230
References 230
Chapter 11: Harmful or Helpful, the Toxicity and Safety of Nano-sized Medicine 241
11.1 Introduction 241
11.1.1 Chapter Overview 241
11.1.2 Paradox of Nanomaterials as Toxins and Therapeutic Agents 242
11.2 Toxicology of Engineered Nanomaterials: Size Really Does Matter 243
11.2.1 Engineering Benefits of Nanomaterials 243
11.2.2 Nanotoxicity 244
11.2.3 Specific Issues Related to Nanomedicines 246
11.2.4 Toxicity Testing of Nano-scale Particles 247
11.3 EC/UK Regulation 248
11.4 Conclusions 251
References 252
Chapter 12: Ethical Implications of Nanomedicine: Implications of Imagining New Futures for Medicine 255
12.1 A Historical Introduction 255
12.2 Generic and Cross-Cutting Ethical Issues 257
12.3 Diagnostics, Information and Predictive Medicine 259
12.4 Remote or Personal Monitoring of Health Status 262
12.5 Implants and Targeted Delivery 264
12.6 Theranostics 265
12.7 Regenerative Medicine 266
12.8 Risk and Uncertainty 266
12.9 Human Enhancement 267
12.10 Conclusions and Postscript 270
References 271
Chapter 13: Nanomedicine: A Hyper-expectation and Dawning Realisation? 274
13.1 Introduction 274
13.2 Popular Media: Feeding Frenzy 278
13.3 The Dawning Implication of Hyper-expectation 280
13.3.1 Nanomedicine: The Cure for Death? 282
13.3.2 Cellular Surgery and Beyond 284
13.3.3 Nano-Doctors: The Perpetual House Call 288
13.3.4 Nanomedicine and Prostheses 289
13.3.5 The Tithonus Error 292
13.3.6 A Brave New World of Nanomedicine 294
13.4 The Boy Who Cried … Self-Assembling Semiconductors! 297
13.5 Nanotoxicology and Regulation 299
13.6 Conclusions and Future Outlook 301
References 302
Chapter 14: Nanomedicine as a Business Venture 308
14.1 The Current Nanomedicine Market 309
14.1.1 Nanomedicine: A Global Market Analysis 309
14.1.1.1 A Market Overview 309
14.1.1.2 A Breakdown per Types of Companies 310
14.1.1.3 Predicting the Nanomedicine Market 310
14.1.2 Nanomedicine: An Overview of the Research and Development Landscape 311
14.1.3 Nanomedicine: An Overview of the Patent Landscape 312
14.1.3.1 A New Era of Commercial Development 312
14.1.3.2 Sectorial and Country Breakdown of Patents in Nanomedicine Worldwide 313
14.2 The Nanomedicine Business Environment 313
14.2.1 Introduction: Key Players in the Nanomedicine Business Environment 313
14.2.2 Nanomedicine Business Drivers 315
14.2.3 Business Models and Strategies 315
14.2.4 The Nanomedicine Business Environment: An Overview of Its Dynamics 317
14.2.5 Current Issues and Future Perspectives 319
14.2.5.1 Current Issues and Strategic Recommendations 319
14.3 Conclusions and Future Perspectives 320
References 321
Chapter 15: What Can Nanomedicine Learn from the Current Developments of Nanotechnology? 323
15.1 Introduction 323
15.2 From Nanotechnology to Nanomedicine 325
15.2.1 A Quick Look at the Current Development in Nanotechnology with a Critical View 325
15.2.2 A Glance of Current Advanced Nanomedicine 327
15.2.2.1 Medical Diagnostics 327
15.2.2.2 Nanomedical Therapeutics 329
15.2.2.3 Multifunctional Nanoparticles: Diagnostics and Therapeutics in a Single System 332
15.2.2.4 Nanotechnology in Regenerative Medicine 333
15.2.2.5 Nanomedicine in Gene Therapy 334
15.3 What Lessons Nanomedicine Can Learn from Nanotechnology? 335
15.3.1 Inconsistency Issues in Nanofabrication 336
15.3.2 Industrial Scale-up and Commercialisation Limitations 336
15.3.3 Complex Nature of Biological Phenomena: Additional Complication to the Complex Concept of Nanoscience, Nanotoxicity and Related Matters 336
15.3.4 Establishment of Standards and Protocols for Nanomaterial Characterisation 337
15.3.5 Nanomedicine Regulating Bodies: A Demand for Proper Regulations 337
15.3.6 Ethical Issues 338
15.4 Conclusions and Future Outlook 339
References 339
Chapter 16: Intersection of Nanotechnology and Healthcare 343
16.1 Introduction – Brief Background of Nanotechnology 343
16.2 Healthcare 344
16.3 Advances of Nanotechnology in Healthcare 345
16.3.1 Applications of Nanotechnology in Imaging 345
16.3.2 Applications of Nanotechnology in Drug Delivery 346
16.3.3 Applications of Nanotechnology in Gene Delivery 347
16.4 Impacts of Nanotechnology on Healthcare 348
16.4.1 Nanotoxicity 349
16.4.2 Nanopharmaceuticals and Food and Drug Administration (FDA) 350
16.5 Regulatory Challenges to Nanotechnology 351
16.6 Rules Governing Nanomedicine 351
16.7 Marketing Prospects of Nanotechnology 352
16.8 Public’s Concern & Prospects on Nanotechnology
16.9 Conclusions and Future Perspectives 354
References 354
Chapter 17: The Impact of Nanopharmaceuticals on Healthcare and Regulation 357
17.1 Introduction 357
17.2 Nanopharmaceuticals in Healthcare 358
17.2.1 Techniques and Advances 358
17.2.2 Positive Impacts 361
17.2.3 Safety and Other Concerns 362
17.3 Nanopharmaceuticals and Regulation 362
17.4 Summary and Future Outlook 364
References 365
Chapter 18: Nanomedicine in Cancer Diagnosis and Therapy: Converging Medical Technologies Impacting Healthcare 367
18.1 Introduction 367
18.2 Nanoparticles for Cancer Imaging and Therapy in Clinical Trials and at Advanced Preclinical Phases of Evaluation 370
18.3 Nanoparticle Applications in Triggered and Image-­Guided Therapies 376
18.4 Conclusions and Future Perspective 379
References 380
Chapter 19: Challenges to Nanomedicine 387
19.1 Introduction 387
19.2 The Rising Costs of Healthcare 388
19.3 The Demographic Shift Towards an Ageing Population 389
19.4 Disruptive Innovation? 391
19.5 Risks and Regulatory Compliance 392
19.6 Health Technology Assessment 396
19.7 Reimbursement and Novel Medical Technologies 398
19.8 Professional Uptake of Nanomedicine 399
19.9 Public Perception 401
19.10 Ethical Considerations and Safeguards 403
19.10.1 What Do We Understand by Healthcare? 403
19.10.2 The Changing Face of Medicine 403
19.10.3 A Data Overload? 404
19.10.4 Non-discrimination and Equity 404
19.10.5 The Precautionary Principle 405
19.11 Training 405
19.12 Conclusions and Perspectives for the Future 406
References 406
Biography of the Editors 409
Dr. Yi Ge 409
Dr. Songjun Li 409
Richard Moore 410
Dr. Shenqi Wang 410
Index 411