Nanoscience and Nanotechnology for Human Health (E-Book) von Bert Müller

Nanomedicine: Present Accomplishments and Far-Reaching Promises XXI

Part One Introduction to Nanoscience in Medicine of the Twenty-First Century 1

1 Challenges and Opportunities of Nanotechnology for Human Health 3
Bert Müller

References 6

2 Nanoscience and Nanotechnology and the Armory for the Twenty-First Century Health Care 9
Marcel Van de Voorde and Pankaj Vadgama

2.1 Conceptual Dream 9

2.2 A Real World Encounter 9

2.3 Mapping the Microcosm of Disease 10

2.4 Delivery at the Clinical Coal Face 10

2.5 A High Precision Aim for Disease Targets 10

2.6 A Materials Revolution for Clinical Care 11

2.7 Robotics for Microrepair and Healing 12

2.8 A Dialog with Cells 12

2.9 Stealth Materials for a More Potent Delivery 13

2.10 Improved Biointerrogation for a Better Understanding 13

2.11 Crossing the StructureFunction Threshold 14

2.12 Living Implants for a Living Matrix 15

2.13 Taming the Nanointerface 15

2.14 Where are We Now? 16

2.15 Where will the Revolution Take Us? 16

2.16 Conclusions 17

References 18

3 Nanomedicine Activities in the United States and Worldwide 21
Carlotta Borsoi, Joy Wolfram, and Mauro Ferrari

3.1 Drug Delivery 22

3.2 Diagnostics 31

3.3 Scaffolds 33

3.4 Clinically Approved Nanoproducts 37

References 39

Part Two Leading Cause of Death: Cardiovascular Diseases 51

4 Challenges in Cardiovascular Treatments Using Nanotechnology-Based Approaches 53
Till Saxer and Margaret N. Holme

4.1 Introduction 53

4.2 Unmet Needs in Cardiology 54

4.3 Nanoparticles for Treatment of CVD 58

4.4 Nanotherapeutics in Surgical Interventions 62

4.5 Conclusions 65

References 66

5 Smart Container for Targeted Drug Delivery 71
Andreas Zumbuehl

5.1 Introduction 71

5.2 Liposomes 72

5.3 Shear Forces and Vesicles 76

5.4 Conclusions 79

References 79

6 Human Nano-Vesicles in Physiology and Pathology 83
Arun Cumpelik and Jürg A. Schifferli

6.1 Introduction 83

6.2 Nomenclature and Definition 84

6.3 Stimulus for Vesicle Release 85

6.4 Overview of Extracellular Vesicle Biology 86

6.5 NVs of Polymorphonuclear Leukocytes 88

6.6 Erythrocyte NVs 89

6.7 Platelet NVs 91

6.8 Conclusions 92

Acknowledgment 93

References 93

7 Challenges and Risks of Nanotechnology in Medicine: An Immunologists Point of View 97
János Szebeni

7.1 Introduction 97

7.2 The Immune Stimulatory Vicious Cycle 98

7.3 The Cause of Immune Recognition of Nanomedicines: Similarity to Viruses 100

7.4 Processes in the Immune Stimulatory Vicious Cycle 101

7.5 Particle Features Influencing the Immune Side Effects of Nanomedicines 109

7.6 Experimental Analysis of the Adverse Immune Effects of Nanomedicines 110

7.7 Decision Tree to Guide the Evaluation of the CARPAgenic Potential of Nanomedicines 113

7.8 Outlook 114

References 114

Part Three Second Most Common Cause of Death: Cancer 125

8 Challenges of Applying Targeted Nanostructures with Multifunctional Properties in Cancer Treatments 127
Jean-Luc Coll and Jungyoon Choi

8.1 Introduction 127

8.2 Enhanced Permeability and Retention Effect 128

8.3 Physicochemical Factors that Influence NP Passive Properties 129

8.4 Targeted NPs 134

8.5 Conclusions 143

Acknowledgments 144

References 145

9 Highly Conformal Radiotherapy Using Protons 157
Antony John Lomax

9.1 Introduction 157

9.2 Proton Physics 161

9.3 Delivering Proton Therapy 165

9.4 Clinical Applications 172

9.5 The Future of Proton Therapy 177

9.6 Is There a Role for Nanotechnology in Proton Therapy? 183

References 186

10 Self-Organization on a Chip: From Nanoscale Actin Assemblies to Tumor Spheroids 191
Cora-Ann Schoenenberger and Thomas Pfohl

10.1 Introduction 192

10.2 Microfluidic Cell Culture 197

10.3 Self-Regulated Loading of Cells into Microchambers 197

10.4 2D Cell Culture in Microfluidics 200

10.5 Expanding Microfluidic Cell Culture to the Third Dimension 200

10.6 Microfluidic Biomimetic Models of Cancer 204

10.7 Future Perspectives 204

Acknowledgments 205

References 205

11 The Nanomechanical Signature of Tissues in Health and Disease 209
Daphne O. Asgeirsson, Philipp Oertle, Marko Loparic, and Marija Plodinec

11.1 Summary 209

11.2 Tissue Mechanics Across Length Scales 210

11.3 Atomic Force Microscopy (AFM) in Cell and Tissue Biology 211

11.4 The Nanomechanical Signature of Articular Cartilage 218

11.5 The Nanomechanical Signature of Mammary Tissues 224

11.6 AFM The Diagnostic and Prognostic Tool of the Future 229

Acknowledgments 232

Competing Financial Interests 232

References 232

Part Four Most Common Diseases: Caries, Musculoskeletal Diseases, Incontinence, Allergies 241

12 Revealing the Nano-Architecture of Human Hard and Soft Tissues by Spatially Resolved Hard X-Ray Scattering 243
Hans Deyhle and Bert Müller

12.1 Introduction 243

12.2 Spatially Resolved Hard X-Ray Scattering 244

12.3 Nanoanatomy of Human Hard and Soft Tissues 251

12.4 Conclusions and Outlook 259

References 259

13 Regenerative Dentistry Using Stem Cells and Nanotechnology 263
Thimios A. Mitsiadis and Giovanna Orsini

13.1 Introduction 263

13.2 Repair of Dental Tissues 264

13.3 Dental Stem Cells and Their Regenerative Potential 265

13.4 Regenerative Dentistry 267

13.5 Nanotechnology in Dentistry 269

13.6 Nanoscale Surface Modifications of Dental Biomaterials 270

13.7 Concluding Remarks 279

Acknowledgments 280

References 280

14 Nanostructured Polymers for Medical Applications 293
Prabitha Urwyler and Helmut Schift

14.1 Introduction 293

14.2 Applications of Nanostructures 295

14.3 Processes for Generation of Nanotopographies 301

14.4 Surface Patterning of Microcantilevers Using Mold Inlays 303

14.5 Surface Patterning Using Plasma Etching 306

14.6 Cell Response to Surface Patterning 308

14.7 Conclusion 309

References 310

15 Nanotechnology in the Treatment of Incontinence 315
Vanessa Leung and Christian Gingert

15.1 Urinary Incontinence 316

15.2 Fecal Incontinence 321

References 327

16 Nanomedicine in Dermatology: Nanotechnology in Prevention, Diagnosis, and Therapy 329
Kathrin Scherer Hofmeier and Christian Surber

16.1 Introduction 329

16.2 Nature of Nanoparticles 330

16.3 Absorption of Nanoparticles through Skin 333

16.4 Nanoparticles in Prevention, Diagnosis, and Therapy 336

16.5 Regulatory Issues 344

16.6 Public Perception of Nanoparticles in Topicals 344

16.7 Conclusions and Future Perspectives 345

References 347

Part Five Benefiting Patients 357

17 Therapeutic Development and the Evolution of Precision Medicine 359
Gareth D. Healey and R. Steven Conlan

17.1 Origins of Nanomedicine 359

17.2 Global Nanomedicine Market 360

17.3 Nanomedicine Cabinet 361

17.4 Application of Nanomedicine A Paradigm Shift 365

17.5 Targeted Drug Discovery and the Human Kinome 367

17.6 Translation from Discovery to the Clinic 369

17.7 Evolution of Kinase Inhibitors 370

17.8 Nanoparticle Delivery 372

17.9 Conclusions 374

References 374

18 Benefit from Nanoscience and Nanotechnology: Benefitting Patients 379
Bert Müller and Marcel H. Van de Voorde

Index 383

Unique in combining the expertise of practitioners from university hospitals and that of academic researchers, this timely monograph presents selected topics catering specifically to the needs and interests of natural scientists and engineers as well as physicians who are concerned with developing nanotechnology-based treatments to improve human health.

To this end, the book cover the materials aspects of nanomedicine, such as the hierarchical structure of biological materials, the imaging of hard and soft tissues and, in particular, concrete examples of nanotechnology-based approaches in modern medical treatments. The whole is rounded off by a discussion of the opportunities and risks of using nanotechnology and nanomaterials in medicine, backed by case studies taken from real life.

Bert Muller is Professor for Materials Science in Medicine at the University of Basel and teaches physics at ETH Zurich. He received a diploma in mechanical engineering, followed by M.Sc. degrees in Physics and English from the Dresden University of Technology, and obtained a PhD in experimental physics from the University of Hannover, Germany. For his achievements he was granted with the Morton M. Traum Award of the American Vacuum Society. Afterwards, he worked as researcher at the Paderborn University, Germany, as Feodor Lynen Fellow and research associate at the EPF Lausanne and as team leader at ETH Zurich. He has become a faculty member of the Physics Department at ETH Zurich. Ten years ago he has founded the Biomaterials Science Center. Currently, this center has more than twenty researchers dealing with nanotechnology-based artificial muscles for incontinence treatment, smart nano-containers to treat cardiovascular diseases, high-resolution X-ray imaging to visualize the human body down to the molecular level, computational sciences of tissues in health and disease and other applications of physics and nanosciences in medicine and dentistry. He is Fellow of SPIE and an active member of the European Academy of Sciences and Arts.

Marcel Van de Voorde has 40 years` experience in European Research Organisations including CERN-Geneva, European Commission, with 10 years at the Max Planck Institute in Stuttgart, Germany. For many years, he was involved in research and research strategies, policy and management, especially in European research institutions. He holds a Professorship at the University of Technology in Delft, the Netherlands, as well as multiple visiting professorships in Europe and worldwide. He holds a doctor honoris causa and various honorary Professorships.
He is senator of the European Academy for Sciences and Arts, in Salzburg and Fellow of the World Academy for Sciences. He is a Fellow of various scientific societies and has been decorated by the Belgian King. He has authored of multiple scientific and technical publications and co-edited multiple books in the field of nanoscience and nanotechnology.