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Contents

Foreword............................................................................................................... xix
Preface����������������������������������������������������������������������������������������������������������������� xxiii
Acknowledgments��������������������������������������������������������������������������������������������� xxv
Author���������������������������������������������������������������������������������������������������������������� xxvii

Part I Perspectives

1. Nanomedicine: Scientific Basis and Societal Implications..................... 3

1.1 Introduction............................................................................................3
1.2 Medicine.................................................................................................. 3
1.3 Nanotechnology.....................................................................................5
1.4 What Is Nanoscience and Where Does It Fit in the Sciences?.........6
1.4.1 Definition and Scientific Basis................................................ 6
1.4.2 Nanotools: The Tools, Techniques,
and Methodologies of Nanoscience.......................................8
1.5 Origins of Nanotechnology..................................................................9
1.6 Molecular and Cell Biology and Protein Bioscience:
A Model of Life as Organic Nanomachinery................................... 12
1.6.1 Bionanotechnology................................................................. 13
1.6.2 Biological and Biomimetic Nanostructures........................ 13
1.6.3 Functional Biological Nanomaterials and
Nanoengines..................................................................... 13
1.6.4 Need for Nanoscience in Description of Life..................... 15
1.7 Nanotechnology Leads to a Fundamentally New Approach
to Engineering Design......................................................................... 15
1.8 Societal and Economic Impacts......................................................... 17
1.9 Impact of Nanotechnology on Medicine.......................................... 19
1.10 The Grand Challenge of Nanotechnology....................................... 19
1.11 Some Definitions and Nanomedical Areas of Emphasis............... 19
1.11.1 Medical Nanotechnology...................................................... 20
1.11.1.1 Advanced Medical Instrumentation................. 20
1.11.1.2 Powering Systems Biology and Theranostics.......21
1.11.1.3 Enabling Distributed Personalized Care.......... 21
1.11.1.4 Medical Materials................................................ 21
1.11.1.5 Nanoparticles for Image Enhancement............22
1.11.1.6 Drug Delivery.......................................................22
1.11.1.7 Overcoming Natural Barriers to Drug
Delivery..............................................................22

v
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1.11.1.8 Protecting Implants from the Immune

System.............................................................. 23
1.11.1.9 Advanced Prosthetics.......................................... 23
1.11.1.10 Advanced Biosensors and Therapeutic
Implants................................................................. 23
1.11.1.11 Guarding against Spread of Disease................. 23
1.11.1.12 Medical Nanotechnology: A Broad Base
for Medical Innovation........................................ 23
1.11.2 Nanomedicine......................................................................... 24
1.12 Healthcare Crisis: How Can Nanotechnology Contribute
to a Solution?......................................................................................... 27
1.12.1 The Wired World.................................................................... 28
1.12.2 Human Augmentation........................................................... 29
1.12.3 Environmental Impacts.......................................................... 29
1.13 Conclusion............................................................................................. 30
References........................................................................................................ 30

2. Historical Perspectives and Technological Breakthroughs.................. 31

2.1 Introduction.......................................................................................... 31
2.2 Brief Highlights of Nanomedicine History...................................... 31
2.2.1 Nanoscience Streams of Development................................ 32
2.2.2 Interrelationship between Nanotech Development
and Medical Development.................................................... 33
2.3 Medical Milestones..............................................................................34
2.3.1 Some Medical Nanotechnology Milestones....................... 36
2.3.2 Some Cautionary Notes for a New Field............................. 39
2.3.3 A Positive Look Forward....................................................... 41
References........................................................................................................ 41

3. Emerging National and Global Nanomedicine Initiatives...................43

3.1 Some Developments in Nanomedicine.............................................43
3.2 Current Examples of Nanomedicine in Practice and Research.......43
3.2.1 Books........................................................................................44
3.2.2 Journals.................................................................................... 46
3.2.3 Web Sites.................................................................................. 47
3.2.4 National Initiatives and Institutes........................................48
3.2.5 Societies.................................................................................... 50
3.2.6 Publications, Patents, and Product Development.............. 51
3.3 NIH Nanomedicine Initiative............................................................ 52
3.3.1 Nanomedicine Research Programs...................................... 53
3.3.2 The NIH Nanomedicine Roadmap...................................... 53
3.3.3 Center for Nucleoprotein Machines..................................... 56
3.4 Putting Medical Nanoscience into Practice: Medical
Nanotechnology and Nanomedicine................................................ 58
References........................................................................................................ 59
Contents vii

Part II Beginnings of Medical Nanotechnology

4. Nanomedicine: Proposals and Promise....................................................63

4.1 Introduction and Overview................................................................63
4.2 Impacts of Nanotechnology on Medicine........................................64
4.2.1 The Natural Evolution of Nanomedicine
from Physics, Chemistry, and Biology................................. 65
4.2.2 Revolutionary Program Proposals....................................... 65
4.2.3 Inevitable Indirect Impacts of Nanotechnology.................65
4.2.4 Effect of Technology on Skilled Practice............................. 66
4.2.5 The Integrated Effect of Three Trends................................. 69
4.3 An Overview of the Architecture of Medical
Nanotechnology and Nanomedicine................................................ 69
4.4 Nanoscience: Bridging the Gap between Biochemistry
and Cell Biology................................................................................... 72
References........................................................................................................ 73

5. Medication: Nanoparticles for Imaging and Drug Delivery................ 75

5.1 Introduction: The Emergence of Nanotechnology
Applications in Medicine.................................................................... 75
5.1.1 Medical Applications of Nanoparticles............................... 76
5.1.2 General Requirements for Use of Nanoparticles...............77
5.2 Nanoparticles for Medical Imaging.................................................. 78
5.2.1 Enhancement for X-Ray and Tomography Imaging.......... 79
5.2.2 Enhancements with MRI Imaging.......................................80
5.2.3 Nanodots and Quantum Resonant Nanoparticles............80
5.2.4 Nanoparticles in the Enhancement of IR, Visible,
and UV Imaging..................................................................... 81
5.2.5 Nanoparticles with Visible and UV Resonance
for Cellular Probes.................................................................. 81
5.2.6 Nanoparticle Image Enhancement for Ultrasound
and Optoacoustic Imaging.................................................... 82
5.3 Nanoparticles for Targeted Imaging and Delivery of Energy......83
5.3.1 Photothermal and Photodynamic Therapies......................83
5.3.2 Combined Radiation and Photodynamic Therapy............ 86
5.3.3 Magnetic Nanoparticles for Targeting Cancer Cells......... 87
5.4 Nanoparticles for Delivery of Drugs................................................. 87
5.4.1 Direct Application of Nanoparticles for Therapy.............. 88
5.4.2 Targeted Drug Delivery......................................................... 88
5.4.3 A Historical Note on Targeted and Nanoparticle
Drug Delivery.......................................................................... 89
5.4.4 Advantages of Nanoparticles for Drug Delivery............... 90
5.4.5 Nanotoxicology....................................................................... 92
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5.4.6 Few Examples of Cellular Nanomachinery Targeted

by Nanodrugs.......................................................................... 93
5.4.6.1 Aspirin: Targeting in the Inflammatory
Response Pathway................................................... 93
5.4.6.2 P-Glycoproteins: Circumventing the
Nanomachinery of the Cell Membrane............... 95
5.4.6.3 Taxol: Disabling the Cell Division
Nanomachinery (Tubulin)..................................... 97
5.4.7 Nanoparticles: Their Materials and Fabrication
for Drug Delivery.................................................................... 99
5.4.7.1 Some Materials and Geometries of Drug
Delivery Nanoparticles.......................................... 99
5.4.7.2 Some Nanoparticle Drug Delivery Systems...... 100
5.4.7.3 Polymers and Polymer Conjugates as Drug
Delivery Vehicles................................................... 103
5.4.8 Nanoencapsulation for Drug Delivery.............................. 110
5.4.8.1 Encapsulation Methods........................................ 110
5.4.8.2 New Designs and Applications
for Therapeutic Nanoparticles and
Nanocapsules...................................................... 114
5.4.8.3 Encapsulation Techniques and Materials
for Proteins and Peptides..................................... 116
5.5 Some Therapeutic Application Areas for Nanoparticles............. 122
5.5.1 Infectious Diseases............................................................... 123
5.5.2 Degenerative and Autoimmune Diseases......................... 123
5.5.3 Nanoparticle Drug Delivery in Cardiology and
Vascular Disease................................................................... 124
5.5.4 Usefulness of Nanoparticles in Otolaryngology............. 124
5.5.5 Ocular Applications of Nanocarrier Drug Delivery........ 124
5.5.6 Nanoparticle Drug Delivery for Neuroinflammatory
Diseases.................................................................................. 125
5.5.7 Nanotherapies for Insulin Delivery................................... 125
5.5.8 Nanoencapsulation for Immunoprotection...................... 128
5.5.9 Nanoparticles for Inhalation Therapy............................... 129
5.5.10 Nanoencapsulation for Penetration of the
Blood–Brain Barrier.............................................................. 130
5.5.11 Nanoparticle Delivery for Cancer Therapy...................... 132
5.5.12 Nanoparticle Delivery of Natural Product Therapies..... 133
5.5.13 Focus on Nanoparticle Therapies for Types
of Cancers........................................................................... 136
5.5.13.1 Pancreatic Cancer.................................................. 136
5.5.13.2 Ovarian and Gynecological Cancers.................. 136
5.5.13.3 Breast Cancer......................................................... 137
5.5.13.4 Prostate Cancer...................................................... 137
Contents ix

5.5.13.5 Lung Cancer........................................................... 137

5.5.13.6 Nanoparticle Targeting of Folic
Acid Receptors for a Variety of Cancers............ 138
5.5.13.7 Epithelial Cancers Targeted by
Hyperthermia and Photothermal Therapy....... 138
5.6 Theranostics........................................................................................ 138
5.6.1 Multifunctional Nanoparticles for Imaging
and Therapy........................................................................... 139
5.6.2 Nanocapsules and Bioreactors with Active
Elements....................................................................... 140
5.6.3 Chemically Activated Release............................................. 140
5.6.4 Photonic Release................................................................... 141
5.6.5 Nanosensor Particle Systems for In Vivo Diagnostics..........143
5.6.6 Nanotechnology for Genetic Screening
and Therapy ................................................................ 145
5.7 Conclusion: Nanomedicines Have a Broad Impact
Throughout Medicine........................................................................ 147
References...................................................................................................... 148

6. Intervention: Nanotechnology in Reconstructive Intervention

and Surgery................................................................................................... 175
6.1 Introduction........................................................................................ 175
6.2 Nanoengineered Materials in Surgical and Restorative
Applications........................................................................................ 175
6.3 Bridging the Gap between Drugs and Surgery with
Endoscopic MEMS............................................................................. 177
6.3.1 Endoscopy, Endoscopic Surgery, and Natural Orifice
Translumenal Endoscopy (NOTES)................................... 178
6.3.1.1 Endoscopic Diagnostic and Surgical
Techniques.............................................................. 178
6.3.1.2 Endoscopic Instrumentation............................... 179
6.3.1.3 MEMS (Microelectromechanical Systems)
for Endoscopic Imaging and Sensing
Modalities............................................................... 180
6.3.2 Access by Catheters: Nanotechnology Impacts................ 182
6.3.3 Techniques for Cerebrospinal Navigation and
Endoscopy.............................................................................. 183
6.4 Robotics in Surgery: The Technology............................................. 184
6.4.1 The Human Interface........................................................... 187
6.4.2 Ergonomics............................................................................ 187
6.4.3 Haptics.................................................................................... 187
6.4.4 Immersive Imaging Systems and Augmented
Environments........................................................................ 188
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6.4.5
Virtual Reality Simulators for Training and
Planning......................................................................... 188
6.4.6 Telerobotics and Telesurgery.............................................. 189
6.4.7 Critiques of Surgical Robotics and Technical Barriers
to Be Overcome..................................................................... 189
6.5 Robotics in Surgical Practice............................................................ 191
6.5.1 Surgical Robotics in Cardiology and Cardiothoracic
Surgery................................................................................... 191
6.5.2 Tracking the Beating Heart................................................. 192
6.5.3 Electrophysiology................................................................. 193
6.5.4 Neurology and Neurosurgery............................................ 193
6.5.5 Head and Neck Surgery and Otorhinolaryngology........ 193
6.5.6 Ophthalmology..................................................................... 194
6.5.7 Oral and Maxillofacial Surgery.......................................... 194
6.5.8 Orthodontics.......................................................................... 195
6.5.9 Craniofacial Surgery............................................................. 195
6.5.10 Plastic and Reconstructive Surgery................................... 196
6.5.11 Orthopedic Surgery.............................................................. 196
6.5.12 Gastrointestinal..................................................................... 197
6.5.13 Hernia..................................................................................... 197
6.5.14 Gallbladder: Cholecystectomy............................................ 198
6.5.15 Liver Surgery......................................................................... 198
6.5.16 Colorectal Surgery................................................................ 200
6.5.17 Urology................................................................................... 200
6.5.18 Renal Surgery........................................................................ 201
6.5.19 Nephrectomy......................................................................... 201
6.5.20 Adrenalectomy...................................................................... 202
6.5.21 Prostatectomy........................................................................ 202
6.5.22 Reproductive Medicine........................................................ 202
6.5.22.1 Varicocelectomy..................................................... 203
6.5.22.2 Vasovasostomy...................................................... 203
6.5.22.3 Gynecology............................................................ 203
6.5.22.4 Obstetrics................................................................ 205
6.5.22.5 Pediatrics................................................................ 205
6.5.23 Image-Guided Robotics in Radiation Oncology.............. 206
6.5.24 Summary of Surgical Robotics in Medical Practice......... 207
6.6 Recent Advances and Emerging Technologies in Surgical
and Endoscopic Navigation.............................................................. 207
6.6.1 Miniaturized and Distributed Control for
Laparoscopic Robotics.......................................................... 208
6.6.2 Robotics for NOTES and LESS............................................ 208
6.6.3 Flexible Robotics: Robotic Activated Endoscopes
and Catheters......................................................................... 210
6.6.4 In Vivo Robotics: Wireless Robotic Navigation for
Diagnosis and Surgery......................................................... 210
Contents xi

6.6.4.1 Capsule Endoscopy............................................... 211

6.6.4.2 Wireless Robotic Modules for Endoscopic
Surgery.................................................................... 213
6.6.5 Integration of Robotics with Biological Materials
Engineering........................................................................... 218
6.7 Summary of Translational Development of Nanoengineered
Regenerative Tissue Therapy............................................................ 219
References...................................................................................................... 220

7. Regeneration: Nanomaterials for Tissue Regeneration....................... 251

7.1 Introduction: The Role of Nanotechnology in Tissue
Regeneration....................................................................................... 251
7.2 Biomaterials for Tissue Regeneration.............................................. 253
7.3 Nanotechnology and Tissue Engineering...................................... 255
7.3.1 Bioactive Scaffold-Guided Tissue Regeneration............... 256
7.3.2 Nanotechnology and Cellular Signaling........................... 257
7.3.3 Cell Transplants and Nanotechnology.............................. 257
7.3.4 Stem Cell–Based Therapies................................................. 258
7.3.5 Future Directions in Stem Cell–Based Tissue
Engineering........................................................................... 259
7.3.6 Nanoencapsulation of Cells and Tissues........................... 259
7.4 Tissue Engineering for Nerve Regeneration.................................. 262
7.4.1 Guiding and Monitoring Nerve Growth........................... 263
7.4.2 Promoting Nerve Repair...................................................... 263
7.4.3 Polylactide Foams................................................................. 265
7.4.4 Polylactide Filaments............................................................ 265
7.4.5 Polylactide Tubules............................................................... 266
7.4.6 Biosynthetic Nerve Implants............................................... 266
7.4.7 Carbon Nanotubes Enhance Cell Adhesion
Surfaces.. ....................................................................... 267
7.4.8 Carbon Nanotube Sheets as Neuron Growth Support.........267
7.4.9 Biocompatibility Issues with Carbon Nanotubes............ 267
7.4.10 Natural Material Scaffolds from Agarose and
Laminin.............................................................................. 268
7.4.11 Natural Material Scaffolds with Collagen......................... 268
7.4.12 Polymer Hydrogels............................................................... 270
7.4.13 Bioengineered Bridges for Neuron Growth...................... 271
7.4.14 Summary of Progress in Peripheral and Spinal
Nerve Regeneration.............................................................. 271
7.5 Nanotechnology for Regeneration of the Brain............................. 272
7.5.1 Strategies for Brain Regeneration....................................... 274
7.5.2 Nanoengineered Materials for Brain Regeneration......... 274
7.5.3 Physical and Biochemical Cues for Regeneration............ 275
7.5.4 Morphologies of Porous Scaffolds...................................... 277
xii Contents

7.6 Use of Nanoengineered Scaffolding with Cells for Central

Nervous System Regeneration......................................................... 280
7.6.1 Translation of Nanoscaffold Neural Cell Therapy
toward Clinical Application................................................ 282
7.6.2 Regeneration for Chronic and Neurodegenerative
Disorders................................................................................ 283
7.6.3 Preventing Oxidative Stress................................................ 283
7.6.4 Polymer-Encapsulated Cells Engineered to Secrete
Neural Regulation Factors...................................................284
7.6.5 Huntington’s Disease...........................................................284
7.6.6 Parkinson’s Disease.............................................................. 285
7.6.7 Alzheimer’s Disease............................................................. 285
7.6.8 Multiple Sclerosis.................................................................. 285
7.6.9 Canavan Disease................................................................... 286
7.6.10 Metachromatic Leukodystrophy........................................ 286
7.6.11 Amyotrophic Lateral Sclerosis............................................ 286
7.6.12 Ocular Neurodegeneration: Glaucoma, Retinitis
Pigmentosa, and Macular Degeneration........................... 287
7.6.13 Severe and Chronic Pain...................................................... 287
7.6.14 Epilepsy.................................................................................. 288
7.6.15 Summary of Translational Development of
Nanoengineered Regenerative Neural Therapy������������� 288
7.7 New Developments in Cell Therapy Accelerated
by Nanoscience and Nanotechnology............................................ 289
7.7.1 Sources of Stem Cells........................................................... 289
7.7.2 Nanoscience- and Nanotechnology-Based
Understanding of Cell Function......................................... 291
7.7.3 Gene Therapy........................................................................ 292
7.7.4 Induced Pluripotent Stem Cells.......................................... 293
7.7.5 Peptide-Induced Pluripotent Stem Cells........................... 295
7.7.6 Cell-Penetrating Transduction Peptides............................ 296
7.7.7 Translational Research for iPSC Therapy.......................... 297
7.7.8 Advances toward Clinical Therapies................................. 298
7.8 Conclusion: Toward Clinical Therapies Based on Integrated
Medical Nanoscience.........................................................................300
References...................................................................................................... 301

8. Restoration: Nanotechnology in Tissue Replacement

and Prosthetics............................................................................................. 319
8.1 Introduction........................................................................................ 319
8.2 Nanoscale Biomaterials and Technologies for Tissue
Engineering......................................................................................... 320
8.2.1 Materials Composition and Methods of Fabrication....... 320
8.2.2 Fabrication of Nanofibrous Scaffolding............................. 321
8.2.3 Carbon Nanotubes in Tissue Scaffolding.......................... 322
Contents xiii

8.2.4 Titanium Dioxide Nanoporous Films................................ 322

8.2.5 Viral and Virus-Like Particles for Tissue Scaffolds......... 323
8.2.6 Large-Scale Fabrication of Nanostructured
Materials.......................................................................... 323
8.2.7 Layer-by-Layer Self-Assembly of Membranes and
Composite Materials............................................................. 324
8.2.8 Nanoskiving.......................................................................... 324
8.2.9 Self-Assembly of Nanomaterials on the
Macromolecular Level.......................................................... 324
8.3 Application of Tissue Engineering in Medicine............................ 327
8.3.1 Experimental Evaluations of Nanoengineered
Tissue Scaffolding................................................................. 328
8.3.2 Smart Materials: Adaptive Nanostructured
Materials for Medical Applications—The Future............ 332
8.3.3 Translation of Nanoengineered Biomaterials into
Clinical Applications............................................................ 332
8.3.3.1 Nanoparticle Materials for Wound Healing.... 332
8.3.3.2 Nanomaterials in Tissue Scaffolding for
Cartilage and Bone................................................ 333
8.3.4 Nanotechnology for Cardiac and Vascular Tissue
Repair......................................................................................... 336
8.3.5 Nanoengineered Encapsulation and Implantation
of Cells and Tissues.............................................................. 337
8.3.5.1 Encapsulation and Implantation
Techniques.. .................................................... 338
8.4 Nanotechnology and Prosthetics.....................................................340
8.4.1 Neuronal Stimulation and Monitoring.............................340
8.4.1.1 Neurostimulation for Pain and Nervous
Disorders................................................................ 341
8.4.2 Neuroprosthetics..................................................................342
8.4.3 Assistive Devices..................................................................342
8.4.4 Types of Neural Prostheses.................................................342
8.4.4.1 Motor Neuroprostheses........................................343
8.4.4.2 Leg, Knee, and Foot Prostheses..........................344
8.4.4.3 Hand Prostheses....................................................345
8.4.5 Brain–Machine Interface...................................................... 347
8.4.5.1 Motor and Sensory Interfaces.............................. 347
8.4.5.2 Promising Breakthroughs in
Brain–Machine Prostheses................................... 347
8.4.5.3 Challenges to Be Overcome................................. 347
8.4.5.4 Design of Control Algorithms.............................348
8.4.5.5 Adaptive Coding and Training........................... 349
8.4.5.6 Distributed Control Networks of
Nanocomputers..................................................... 349
8.4.5.7 Noninvasive Brain–Machine Interfaces............. 350
xiv Contents

8.4.6 Magnetic Neural Stimulation and Monitoring................ 351

8.4.6.1 Basic Principles...................................................... 351
8.4.6.2 Magnetic Stimulation........................................... 351
8.4.6.3 Development of Medical Applications............... 352
8.4.6.4 Magnetic Monitoring............................................ 352
8.4.6.5 Devices for Magnetic Stimulation
and Monitoring...................................................... 353
8.4.6.6 Nanotechnology-Based Advances
in Magnetic Sensor Design..................................354
8.4.6.7 Future Opportunities in Medical Magnetic
Sensing.................................................................... 356
8.4.7 Sensory Neuroprosthetics: Haptics.................................... 356
8.4.8 Cognitive Prosthetics........................................................... 357
8.4.9 Future Directions for Brain–Machine Interfaces.............. 357
8.4.10 Neuroprosthetics for the Ear............................................... 358
8.4.10.1 Neuroprosthesis for Balance............................... 359
8.4.10.2 Neuroprosthesis for Tinnitus.............................. 360
8.4.10.3 Anatomy of the Ear............................................... 360
8.4.10.4 Design of Cochlear Implants............................... 361
8.4.11 Vision Prosthetics................................................................. 362
8.4.11.1 The Retina.............................................................. 363
8.4.11.2 Fovea....................................................................... 363
8.4.11.3 Bypassing the Retina............................................364
8.4.11.4 Artificial Retinas...................................................364
8.4.11.5 Other Research on Vision Prosthetics................ 366
8.5 Summary of Nanoengineered Restorative Tissue
Engineering and Prosthetics............................................................ 367
References...................................................................................................... 367

9. Diagnosis: Nanosensors in Diagnosis and Medical Monitoring...... 387

9.1 Introduction........................................................................................ 387
9.2 Overview............................................................................................. 387
9.3 Sensors: Nanotechnology-Driven Advances in Diagnostic
and Monitoring Technology............................................................. 388
9.3.1 Examples of Nanosensors.................................................... 389
9.3.1.1 Cantilever Sensors................................................. 389
9.3.1.2 Active Cantilever Sensors.................................... 390
9.3.1.3 Passive Cantilever Sensors................................... 391
9.3.1.4 Surface Effects on Nanocantilevers.................... 391
9.3.1.5 Steric Effects........................................................... 392
9.3.1.6 Micro- and Nanosensors and Applications...... 392
9.3.1.7 Biomedical Cantilever Applications................... 392
9.3.1.8 Surface Plasmon Nanosensors............................ 393
Contents xv

9.3.2 Nanosensor Technologies.................................................... 394

9.3.2.1 Nanosensor Fabrication........................................ 394
9.3.2.2 An Example of Sensor Protection by
Nanofabrication..................................................... 394
9.3.2.3 Making Sensors Bio-Specific: Antibodies,
Antigens, Templates, and Aptamers.................. 397
9.3.2.4 Sensors for Physiological Parameters................. 399
9.3.2.5 Sensors for Nerve Activity...................................400
9.3.3 Integrated Nanosensor Technologies................................ 401
9.3.3.1 Integration of Nanosensors with Fiber
Optics................................................................... 401
9.3.3.2 BioMEMS for Integration with Sensors............. 402
9.3.3.3 Microfluidics and Nanofluidics........................... 402
9.3.3.4 Manipulation and Imaging of Cells,
Particles, and Fluids.............................................. 403
9.3.3.5 Dielectrophoresis................................................... 403
9.3.3.6 Optical Tweezers and Photonic Vortex Traps....... 404
9.3.3.7 Electrokinetics on Hydrophobic Surfaces..........404
9.3.3.8 Microfluidics and Nanotechnology in Mass
Spectrometry..........................................................405
9.3.3.9 Mass Spectrometry Imaging............................... 406
9.3.3.10 Imaging with Functional MRI............................ 406
9.3.4 Summary: From Separate Sensors to Labs on Chips....... 408
9.4 Technologies for Genomics and Proteomics.................................. 408
9.4.1 Genomics, Proteomics, and Personalized Medicine........ 408
9.4.1.1 Gene Amplification—A Basic Technique
for DNA Measurement.........................................409
9.4.1.2 Technology for DNA Sequencing....................... 411
9.4.1.3 Genetic Screening and Genomic Medicine....... 413
9.4.2 Analyzing the Proteome...................................................... 414
9.4.2.1 Protein Analysis by Mass Spectrometry........... 415
9.4.2.2 Protein Analysis Array BioChips........................ 415
9.4.3 The Metabolome: The Emerging Concept of
Metabolomics........................................................................ 416
9.5 Applied Genomics and Proteomics: From Personalized
Medicine to Global Epidemiology................................................... 417
9.5.1 Systems Biology.................................................................... 418
9.5.2 Genomics, Proteomics, and Cancer.................................... 418
9.5.3 Genomics, Proteomics, and Immunology......................... 419
9.5.4 Personalized Medicine for Complex Multigenomic
Disorders................................................................................ 420
9.5.5 Monitoring for Disease........................................................ 421
9.6 Real-Time and In Vivo Medical Monitoring.................................. 421
9.6.1 Patient Monitoring in Clinic and Hospital........................422
xvi Contents

9.6.2 Personal Monitoring.............................................................422

9.7 Conclusion...........................................................................................423
References...................................................................................................... 423

Part III Future Directions and Transformations

10. Thesis, Antithesis, Synthesis: Integrated Biomolecular

Nanoscience.................................................................................................. 455
10.1 Maturation of Medical Nanotechnologies...................................... 455
10.2 Continued Impacts of Nanotechnology- Driven Capabilities...... 455
10.3 Nanotechnologies in Translation from Research.......................... 456
10.4 Indirect Impacts of Nanotechnology-Enabled Systems
on Practice........................................................................................... 457
10.5 Translation of Medical Nanotechnologies into Clinical
Practice................................................................................................. 458
References...................................................................................................... 459

11. Challenging Boundaries: Life and Material, Self and

Environment................................................................................................. 461
11.1 Nanotechnology and Medicine: A Powerful Confluence............ 461
11.2 Historical Origins of Medical Traditions........................................ 462
11.3 Knowledge of the Genome...............................................................464
11.3.1 Should an Individual Have the Right Not to Know
Their Genome: The “Right to Ignorance”?........................464
11.3.2 Cultural Diversity in Attitudes toward Personal
Control....................................................................................464
11.4 Replacement Parts for the Body.......................................................464
11.5 Augmentation of Human Characteristics and Abilities...............464
11.6 Extension of Life................................................................................. 465
11.7 Issues with Transplanted Cells for Regeneration.......................... 466
11.8 Medicalization of Normal Conditions............................................ 466
11.9 Other Boundaries Yet More Weird.................................................. 466
11.10 Summary............................................................................................. 467
References...................................................................................................... 467

12. Sustainability and Future Choices for Societies................................... 473

12.1 Nanotechnology and Medicine as a Socioeconomic
Activity...................................................................................... 473
12.2 Questions of Change......................................................................... 473
12.2.1 Disruptive Technology......................................................... 474
12.2.2 Impacts on Medical Practice............................................... 475
12.2.3 Impact of Technological Developments on Personal
Healthcare.............................................................................. 475
Contents xvii

12.2.3.1 Evolution of Choice in Healthcare...................... 476

12.2.3.2 Standardization of Care and Mass
Production of Drugs............................................. 477
12.2.3.3 New Needs of Personalized Medicine
in Cancer and Infectious Disease....................... 477
12.2.4 Distribution and Extension of Healthcare
by Telecommunications and Nanosensors....................... 478
12.2.5 Synergistic Economic Impact of Nanomedicines
with Biotechnology and Genomics.................................... 478
12.2.6 Restorative and Regenerative Medicine............................ 479
12.2.7 Global Divide......................................................................... 479
12.2.8 The Threat of Grey Goo.......................................................480
12.3 Conclusion........................................................................................... 481
References...................................................................................................... 481
Index......................................................................................................................485
Foreword

This book, Medical Nanotechnology and Nanomedicine, is an introduction to

nanoscience and nanotechnology for those with medical backgrounds and
interests. It is an overview and guide, with references and keywords for fur-
ther pursuit into the rapidly growing fields of medical nanotechnology and
nanomedicine. It is meant for the layperson, in the sense of both the non-
medical specialist and the nontechnical healthcare professional.
The currently available literature as well as various media sources on nano-
technology contain a number of differing views of the impact of nanotech-
nology on the future of medicine. This book gives an overview of the many
alternative and sometimes conflicting concepts proposed for the application
of nanotechnology to medicine, along with a review of some recent research
and development, illustrating the accomplishments and possibilities for the
application of nanoscience to medicine.
Just as with nanotechnology in general, popularized presentations of nano-
medicine have included a variety of viewpoints, from futuristic and specula-
tive visions to rather straightforward applications of existing techniques on a
limited scale. But nanomedicine and medical nanotechnology are taking an
interesting and promising direction. The terms “nanomedicine” and “medi-
cal nanotechnology” have been formally established since their adoption into
major program initiatives by the National Institutes of Health and other lead-
ing medical bodies worldwide. Leading pharmaceutical and medical device
companies have set up their own departments focused on nanomedicine and
have been joined by a number of start-up enterprises, backed, in some cases,
by investment groups focused on medical nanotechnology ventures.
In an environment full of news about nanotechnology, the general reader
(including the medical professional not particularly familiar with nanotech-
nology) will do well to get started with an introduction to nanomedicine
and its evolving organizational infrastructure, both available and proposed.
An exhaustive, technical coverage of nanotechnology applied to biomedical
areas does not serve the purpose as an introduction, nor do futuristic projec-
tions that have little to do with actual medical practice. This book intends
to provide a practical guide about nanomedicine for the interested, curious,
or perplexed individual. It is intended for laypersons, patients, and medical
practitioners and professionals who are looking for a clear understanding
of the rapidly developing nanotechnology revolution impacting their field
of work. Medical professionals are used to rapid and sometimes transfor-
mational advances in technology and practices. Planning, investment, and
continuing medical education are directed at constantly moving targets.
Although conservative and skeptical of new claims, the medical profession
is constantly seeking to evaluate new possibilities for breakthroughs.

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