Nanoscience and Nanotechnology for Human Health E-Book
151,99 €
Mehr erfahren.
- Herausgeber: Wiley-VCH Verlag GmbH & Co. KGaA
- Kategorie: Fachliteratur
- Serie: Nanotechnology Innovation & Applications
- Sprache: Englisch
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.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 788
Veröffentlichungsjahr: 2016
Ähnliche
Contents
Cover
Series Page
Title Page
Copyright
Dedication
Series Editor Preface
About the Series Editor
Nanomedicine: Present Accomplishments and Far-Reaching Promises
Part One: Introduction to Nanoscience in Medicine of the Twenty-First Century
Chapter 1: Challenges and Opportunities of Nanotechnology for Human Health
References
Chapter 2: Nanoscience and Nanotechnology and the Armory for the Twenty-First Century Health Care
2.1 Conceptual Dream
2.2 A Real World Encounter
2.3 Mapping the Microcosm of Disease
2.4 Delivery at the Clinical “Coal Face”
2.5 A High Precision Aim for Disease Targets
2.6 A Materials Revolution for Clinical Care
2.7 Robotics for Microrepair and Healing
2.8 A Dialog with Cells
2.9 Stealth Materials for a More Potent Delivery
2.10 Improved Biointerrogation for a Better Understanding
2.11 Crossing the Structure–Function Threshold
2.12 Living Implants for a Living Matrix
2.13 Taming the Nanointerface
2.14 Where are We Now?
2.15 Where will the Revolution Take Us?
2.16 Conclusions
References
Chapter 3: Nanomedicine Activities in the United States and Worldwide
3.1 Drug Delivery
3.2 Diagnostics
3.3 Scaffolds
3.4 Clinically Approved Nanoproducts
References
Part Two: Leading Cause of Death: Cardiovascular Diseases
Chapter 4: Challenges in Cardiovascular Treatments Using Nanotechnology-Based Approaches
4.1 Introduction
4.2 Unmet Needs in Cardiology
4.3 Nanoparticles for Treatment of CVD
4.4 Nanotherapeutics in Surgical Interventions
4.5 Conclusions
References
Chapter 5: Smart Container for Targeted Drug Delivery
5.1 Introduction
5.2 Liposomes
5.3 Shear Forces and Vesicles
5.4 Conclusions
References
Chapter 6: Human Nano-Vesicles in Physiology and Pathology
6.1 Introduction
6.2 Nomenclature and Definition
6.3 Stimulus for Vesicle Release
6.4 Overview of Extracellular Vesicle Biology
6.5 NVs of Polymorphonuclear Leukocytes
6.6 Erythrocyte NVs
6.7 Platelet NVs
6.8 Conclusions
Acknowledgment
References
Chapter 7: Challenges and Risks of Nanotechnology in Medicine: An Immunologist's Point of View
7.1 Introduction
7.2 The Immune Stimulatory Vicious Cycle
7.3 The Cause of Immune Recognition of Nanomedicines: Similarity to Viruses
7.4 Processes in the Immune Stimulatory Vicious Cycle
7.5 Particle Features Influencing the Immune Side Effects of Nanomedicines
7.6 Experimental Analysis of the Adverse Immune Effects of Nanomedicines
7.7 Decision Tree to Guide the Evaluation of the CARPAgenic Potential of Nanomedicines
7.8 Outlook
References
Part Three: Second Most Common Cause of Death: Cancer
Chapter 8: Challenges of Applying Targeted Nanostructures with Multifunctional Properties in Cancer Treatments
8.1 Introduction
8.2 Enhanced Permeability and Retention Effect
8.3 Physicochemical Factors that Influence NP Passive Properties
8.4 Targeted NPs
8.5 Conclusions
Acknowledgments
References
Chapter 9: Highly Conformal Radiotherapy Using Protons
9.1 Introduction
9.2 Proton Physics
9.3 Delivering Proton Therapy
9.4 Clinical Applications
9.5 The Future of Proton Therapy
9.6 Is There a Role for Nanotechnology in Proton Therapy?
References
Chapter 10: Self-Organization on a Chip: From Nanoscale Actin Assemblies to Tumor Spheroids
10.1 Introduction
10.2 Microfluidic Cell Culture
10.3 Self-Regulated Loading of Cells into Microchambers
10.4 2D Cell Culture in Microfluidics
10.5 Expanding Microfluidic Cell Culture to the Third Dimension
10.6 Microfluidic Biomimetic Models of Cancer
10.7 Future Perspectives
Acknowledgments
References
Chapter 11: The Nanomechanical Signature of Tissues in Health and Disease
11.1 Summary
11.2 Tissue Mechanics Across Length Scales
11.3 Atomic Force Microscopy (AFM) in Cell and Tissue Biology
11.4 The Nanomechanical Signature of Articular Cartilage
11.5 The Nanomechanical Signature of Mammary Tissues
11.6 AFM – The Diagnostic and Prognostic Tool of the Future
Acknowledgments
Competing Financial Interests
References
Part Four: Most Common Diseases: Caries, Musculoskeletal Diseases, Incontinence, Allergies
Chapter 12: Revealing the Nano-Architecture of Human Hard and Soft Tissues by Spatially Resolved Hard X-Ray Scattering
12.1 Introduction
12.2 Spatially Resolved Hard X-Ray Scattering
12.3 Nanoanatomy of Human Hard and Soft Tissues
12.4 Conclusions and Outlook
References
Chapter 13: Regenerative Dentistry Using Stem Cells and Nanotechnology
13.1 Introduction
13.2 Repair of Dental Tissues
13.3 Dental Stem Cells and Their Regenerative Potential
13.4 Regenerative Dentistry
13.5 Nanotechnology in Dentistry
13.6 Nanoscale Surface Modifications of Dental Biomaterials
13.7 Concluding Remarks
Acknowledgments
References
Chapter 14: Nanostructured Polymers for Medical Applications
14.1 Introduction
14.2 Applications of Nanostructures
14.3 Processes for Generation of Nanotopographies
14.4 Surface Patterning of Microcantilevers Using Mold Inlays
14.5 Surface Patterning Using Plasma Etching
14.6 Cell Response to Surface Patterning
14.7 Conclusion
References
Chapter 15: Nanotechnology in the Treatment of Incontinence
15.1 Urinary Incontinence
15.2 Fecal Incontinence
References
Chapter 16: Nanomedicine in Dermatology: Nanotechnology in Prevention, Diagnosis, and Therapy
16.1 Introduction
16.2 Nature of Nanoparticles
16.3 Absorption of Nanoparticles through Skin
16.4 Nanoparticles in Prevention, Diagnosis, and Therapy
16.5 Regulatory Issues
16.6 Public Perception of Nanoparticles in Topicals
16.7 Conclusions and Future Perspectives
References
Part Five: Benefiting Patients
Chapter 17: Therapeutic Development and the Evolution of Precision Medicine
17.1 Origins of Nanomedicine
17.2 Global Nanomedicine Market
17.3 Nanomedicine Cabinet
17.4 Application of Nanomedicine – A Paradigm Shift
17.5 Targeted Drug Discovery and the Human Kinome
17.6 Translation from Discovery to the Clinic
17.7 Evolution of Kinase Inhibitors
17.8 Nanoparticle Delivery
17.9 Conclusions
References
Chapter 18: Benefit from Nanoscience and Nanotechnology: Benefitting Patients
Index
End User License Agreement
List of Tables
Table 6.1
Table 7.1
Table 7.2
Table 7.3
Table 7.4
Table 8.1
Table 11.1
Table 14.1
Table 15.1
Table 15.2
Table 15.3
List of Illustrations
Figure 3.1
Figure 3.2
Figure 3.3
Figure 4.1
Figure 4.2
Figure 4.3
Figure 4.4
Figure 4.5
Figure 5.1
Figure 5.2
Figure 5.3
Figure 5.4
Figure 5.5
Figure 6.1
Figure 6.2
Figure 6.3
Figure 6.4
Figure 7.1
Figure 7.2
Figure 7.3
Figure 7.4
Figure 7.5
Figure 7.6
Figure 7.7
Figure 8.1
Figure 8.2
Figure 8.3
Figure 9.1
Figure 9.2
Figure 9.3
Figure 9.4
Figure 9.5
Figure 9.6
Figure 9.7
Figure 9.8
Figure 9.9
Figure 10.1
Figure 10.2
Figure 10.3
Figure 10.4
Figure 10.5
Figure 10.6
Figure 10.7
Figure 10.8
Figure 10.9
Figure 10.10
Figure 11.1
Figure 11.2
Figure 11.3
Figure 11.4
Figure 11.5
Figure 11.6
Figure 11.7
Figure 11.8
Figure 11.9
Figure 11.10
Figure 11.11
Figure 11.12
Figure 11.13
Figure 12.1
Figure 12.2
Figure 12.3
Figure 12.4
Figure 12.5
Figure 12.6
Figure 12.7
Figure 12.8
Figure 12.9
Figure 12.10
Figure 12.11
Figure 12.12
Figure 13.1
Figure 13.2
Figure 13.3
Figure 13.4
Figure 13.5
Figure 14.1
Figure 14.2
Figure 14.3
Figure 14.4
Figure 14.5
Figure 14.6
Figure 14.7
Figure 14.8
Figure 14.9
Figure 14.10
Figure 14.11
Figure 14.12
Figure 14.13
Figure 15.1
Figure 15.2
Figure 15.3
Figure 15.4
Figure 16.1
Figure 16.2
Figure 16.3
Figure 17.1
Figure 17.2
Figure 17.3
Figure 17.4
Guide
Cover
Table of Contents
Begin Reading
Part 1
Chapter 1
Pages
i
ii
iii
iv
v
vi
vii
viii
ix
x
xxi
xxii
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
Further Volumes of the Series “Nanotechnology Innovation & Applications”
Axelos, M. A. V. and Van de Voorde, M. (eds.)
Nanotechnology in Agriculture and Food Science
2017
Print ISBN: 9783527339891
Cornier, J., Kwade, A., Owen, A., Van de Voorde, M. (eds.)
Pharmaceutical Nanotechnology
Innovation and Production
2017
Print ISBN: 9783527340545
Fermon, C. and Van de Voorde, M. (eds.)
Nanomagnetism
Applications and Perspectives
2017
Print ISBN: 9783527339853
Mansfield, E., Kaiser, D. L., Fujita, D., Van de Voorde, M. (eds.)
Metrology and Standardization for Nanotechnology
Protocols and Industrial Innovations
2017
Print ISBN: 9783527340392
Meyrueis, P., Sakoda, K., Van de Voorde, M. (eds.)
Micro- and Nanophotonic Technologies
2017
Print ISBN: 9783527340378
Puers, R., Baldi, L., van Nooten, S. E., Van de Voorde, M. (eds.)
Nanoelectronics
Materials, Devices, Applications
2017
Print ISBN: 9783527340538
Raj, B., Van de Voorde, M., Mahajan, Y. (eds.)
Nanotechnology for Energy Sustainability
2017
Print ISBN: 9783527340149
Sels, B. and Van de Voorde, M. (eds.)
Nanotechnology in Catalysis
Applications in the Chemical Industry, Energy Development, and Environment Protection
2017
Print ISBN: 9783527339143
Edited by Bert Müller and Marcel Van de Voorde
Nanoscience and Nanotechnology for Human Health
All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.
Library of Congress Card No.: applied for
British Library Cataloguing-in-Publication DataA catalogue record for this book is available from the British Library.
Bibliographic information published by the Deutsche NationalbibliothekThe Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.d-nb.de.
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany
All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.
Print ISBN: 978-3-527-33860-3ePDF ISBN: 978-3-527-69204-0ePub ISBN: 978-3-527-69206-4Mobi ISBN: 978-3-527-69207-1oBook ISBN: 978-3-527-69205-7
Thanks to my wife for her patience with me spending many hours working on the book series through the nights and over weekends. The assistance of my son Marc Philip related to the complex and large computer files with many sophisticated scientific figures is also greatly appreciated.
Marcel Van de Voorde
Series Editor Preface
Since years, nanoscience and nanotechnology have become particularly important technology areas worldwide. As a result, there are many universities that offer courses as well as degrees in nanotechnology. Many governments including European institutions and research agencies have vast nanotechnology programmes and many companies file nanotechnology-related patents to protect their innovations. In short, nanoscience is a hot topic!
Nanoscience started in the physics field with electronics as a forerunner, quickly followed by the chemical and pharmacy industries. Today, nanotechnology finds interests in all branches of research and industry worldwide. In addition, governments and consumers are also keen to follow the developments, particularly from a safety and security point of view.
This books series fills the gap between books that are available on various specific topics and the encyclopedias on nanoscience. This well-selected series of books consists of volumes that are all edited by experts in the field from all over the world and assemble top-class contributions. The topical scope of the book is broad, ranging from nanoelectronics and nanocatalysis to nanometrology. Common to all the books in the series is that they represent top-notch research and are highly application-oriented, innovative, and relevant for industry.
The titles of the volumes in the series are as follows:
Human-related nanoscience and nanotechnology
Nanoscience and Nanotechnology for Human Health
Pharmaceutical Nanotechnology
Nanotechnology in Agriculture and Food Science
Nanoscience and nanotechnology in information and communication
Nanoelectronics
Micro- and Nanophotonic Technologies
Nanomagnetism: Perspectives and Applications
Nanoscience and nanotechnology in industry
Nanotechnology for Energy Sustainability
Metrology and Standardization of Nanomaterials
Nanotechnology in Catalysis: Applications in the Chemical Industry, Energy Development, and Environmental Protection
The book series appeals to a wide range of readers with backgrounds in physics, chemistry, biology, and medicine, from students at universities to scientists at institutes, in industrial companies and government agencies and ministries.
Ever since nanoscience was introduced many years ago, it has greatly changed our lives – and will continue to do so!
March 2016 Marcel Van de Voorde
About the Series Editor
Marcel Van de Voorde, Prof. Dr. ir. Ing. Dr. h.c., has 40 years' experience in European Research Organisations, including CERN-Geneva and the European Commission, with 10 years at the Max Planck Institute for Metals Research, Stuttgart. For many years, he was involved in research and research strategies, policy, and management, especially in European research institutions.
He has been a member of many Research Councils and Governing Boards of research institutions across Europe, the United States, and Japan. In addition to his Professorship at the University of Technology in Delft, the Netherlands, he holds multiple visiting professorships in Europe and worldwide. He holds a doctor honoris causa and various honorary professorships.
He is a senator of the European Academy for Sciences and Arts, Salzburg, and Fellow of the World Academy for Sciences. He is a member of the Science Council of the French Senate/National Assembly in Paris. He has also provided executive advisory services to presidents, ministers of science policy, rectors of Universities, and CEOs of technology institutions, for example, to the president and CEO of IMEC, Technology Centre in Leuven, Belgium. He is also a Fellow of various scientific societies. He has been honored by the Belgian King and European authorities, for example, he received an award for European merits in Luxemburg given by the former President of the European Commission. He is author of multiple scientific and technical publications and has coedited multiple books, especially in the field of nanoscience and nanotechnology.
Nanomedicine: Present Accomplishments and Far-Reaching Promises
The symbolic dawn of nanotechnology is often ascribed to Richard Feynman's address to the American Physical Society in 1959: “There is plenty of room at the bottom..” Possible applications to medicine rapidly appeared as of major importance encompassing in vitro diagnosis, in vivo imaging, and therapeutics. It has been, however, necessary to wait until 1995 to have the first nanodrug approved by the US Food and Drug Administration – a liposomal formulation of doxorubicin termed Doxil®. At present, there are over 300 nanodrugs in various stages of clinical development. All of them, that have been already approved, rely on passive targeting: These compounds are accumulated in tumor tissue due to the existence of leaky, abnormally fenestrated blood vessels and also due to altered lymphatic circulation (EPR (enhanced permeability and retention effect)). Nanocarriers conjugated with antibodies or physiological ligands and thus specifically targeted to cells expressing the corresponding markers are the next step in the development of nanotherapeutics. Such drugs are expected to display a markedly increased therapeutic index, that is, increased effect on tumor tissue and decreased general toxicity. Several of them are now in the late stages of clinical studies and should become available soon. Future developments include theranostics and personalized nanomedicine. Theranostics consist in the presence of therapeutic and imaging compounds in the same carriers specifically targeted to tumor cells. A major advantage of this technology would be the possibility of noninvasive monitoring of early response to therapy and thus to rapid adaptation of the treatment. Personalized nanomedicine will allow the selection of nanodrugs specifically for each patient according to molecular markers (“-omics” data). In this respect, RNA interference seems a promising approach. In parallel to this progress, in diagnostics and therapy, it will be necessary to develop toxicology. The toxicity of a compound changes markedly when the latter is reduced at the nanometer scale. Besides toxicity, due to their shape – “asbestos-like” properties of carbon nanotubes – nanoparticle detrimental effects derive from generation of reactive oxygen species, cellular structure disruption, and immunological reactions. A great progress in the clinical development of nanodrugs would be the availability of in vitro assays able to predict in vivo toxicity.
Nanoparticles are rapidly extending their use in industry: paints, electronics, tires, sport equipment, sunscreens, and so on. The possible toxicity of these compounds present in our environment should be examined. We should also keep in mind and try to prevent the possibility of most dreadful developments: the weaponization of the processes and compounds. The future of nanomedicine is obviously bright. It is bound to become one of our most important tools for diagnosis and therapy.
Member of the French Academy of Medicine Edwin Milgrom
Part OneIntroduction to Nanoscience in Medicine of the Twenty-First Century
1Challenges and Opportunities of Nanotechnology for Human Health
Bert Müller
University of Basel, Department of Biomedical Engineering, Biomaterials Science Center, Gewerbestrasse 14, 4123 Allschwil, Switzerland
Medical doctors have a wide variety of experiences with patients. Therefore, they are generally fast in the evaluation of the entire human body. For example, looking at the morphology of the human body, they can identify the chronic inflammatory disease of the axial skeleton, termed ankylosing spondylitis, previously known as Bekhterev's disease. For many natural scientists and engineers, these abilities are fascinating and surprising, at once.
For the diagnosis of an increasing number of diseases, however, a more detailed evaluation, for example, on the basis of radiological data, is necessary. The amount of high-resolution data obtained is huge and usually overburdens the medical experts. Interdisciplinary cooperation with computer scientists to (semi)automatically analyze the imaging data becomes more and more common. These assessments are often expensive and time-consuming. Nonetheless, the available clinical imaging modalities even with the best spatial resolution do not reach the resolution needed to visualize individual biological cells with sizes of about 10 µm. To this end, it appears dubious, why patients can benefit from nanotechnology.
Reading the instruction leaflets of currently available sun crèmes or sensitive toothpastes, we realize, however, that nanotechnology has reached our daily routine. This book will hardly deal with these well-established, systemic applications, we have known from pharmacy for decades, but with the impact of nanotechnology on dedicated future therapies for the most important diseases.
The leading cause of death in our society relates to cardiovascular diseases [1]. Therefore, the first part of this book, which consists of four chapters from medical experts, that is, cardiologist, internist, immunologist, and natural scientists, targets current research activities toward nonsystemic treatments. For example, nitroglycerin is currently administered to widen the constricted atherosclerotic arteries in a systemic fashion. The vasodilator widens all arteries and veins with serious side effects, including a drastic blood pressure drop. Therefore, the nitroglycerin dose has to be kept limited. Specific biomarkers for this prevalent inflammation do not exist. Consequently, researchers proposed to exploit the wall shear stress increased at constricted arteries with respect to the healthy parts as purely physical trigger to release drugs from mechanosensitive containers or particles of nanometer size [2,3]. These nanotechnology-based innovations are sweeping the established cardiovascular treatments, especially before the patients reach the operating room and endovascular devices for intra-arterial clot lysis, stent implantation, or arterial balloon dilatation could become effective [4].
Second most common cause of death is cancer. It is, therefore, not surprising that the second part of the book is dedicated to alternative diagnoses and treatments of cancer. Although one can cleverly combine pharmaceutical, surgical, and radiation treatments to heal patients, alternative strategies to fight against cancer are more than desirable. The four related chapters depict how contemporary methods and sophisticated materials can contribute to a reliable diagnosis and, more important, to powerful treatments of cancerous tissues even deeply inside the human body difficult to reach. Here, the deep understanding of the physical interactions between the probes such as photons or protons and the biological matter is essential for the selection and the future development of treatment strategies for the general public.
The third part of the book relates to the most common diseases, which are caries, musculoskeletal diseases, incontinence, and allergies. Although they often do not result in death, they massively influence our quality of life.
Caries is the most common infectious bacterial diseases in the world [5]. The disease first destroys the human enamel, which is a unique biologically ordered material with hydroxyapatite crystallites being organized into a fibrous continuum. In healthy state, it remains stable for decades and centuries or even millennia. Currently, no engineering process exists to biomimetically repair this unique biological material with a well-defined nanostructural organization. Therefore, the burden of dental caries lasts for a lifetime. Once the tooth structure is destroyed, it will usually need restoration and additional maintenance throughout life. In addition, the economic impact of such therapeutic approaches is enormous. The World Health Organization estimated that the dental treatment costs accounted for 5–10% of healthcare budgets in industrialized countries and additional costs are caused through absences from work [6,7]. So far, treatments rely on mechanical replacement of decayed tissue by inert biomaterials such as isotropic polymers or composites. Recently, the analysis of the healthy and diseased crowns down to the nanometer scale has led to the necessary anatomical knowledge to develop biomimetic dental fillings, which contain elongated nanostructures with the orientations present in dentin and enamel [8]. Furthermore, the detailed analysis of the caries pathology using X-ray scattering has shown that while bacterial processes dissolve the minerals in enamel and dentin, the dentinal collagen network remains unaffected, enabling the development of treatments to remineralize the dentin [9,10].
The musculoskeletal system demands increasingly frequent treatments with metallic load-bearing implants, which include artificial hips, knees, and dental implants. In general, these metals integrate well into the bone because the sandblasted and etched oxide surface contains a multiplicity of features on the micro- and nanometer scale, which exhibit similarities to the nanometer-size minerals in bone. Therefore, it has been stated that the morphology of the implant's surface tends to have a greater effect than chemical patterns, when both chemical patterns and topographic ones are offered to biological cells [11]. The vital role of the nanostructures in avoiding inflammatory reactions and in reaching cytocompatibility was demonstrated using nanopyramids naturally formed in heteroepitaxy of semiconductors [12,13]. In contrast to metals, high-performance polymers are radiolucent and magnetic resonance imaging compatible, which allow the diagnostic examination of tissues in implant's vicinity. Only recently, the systematic polymer structuring on the nanometer scale for centimeter-size implants was explored [14]. It is relatively easy to produce micro- and nanostructures with a preferential orientation, which better mimic the anisotropy of the bony tissues within our body [15]. Therefore, one can reasonably expect that polymeric load-bearing implants will be employed in near future at least for dedicated cases.
The aging of our society has led to the increasing prevalence of social and economic burdening by age-related diseases, including urinary and fecal incontinence. In comparatively simple cases, conservative therapy is successful. Surgical therapy is advisable for more complex cases, where the extent of surgery depends on the severity. In severe cases, artificial sphincter systems are applied, which currently rely on fluid-filled cuffs. So far, they are not part of everyday surgical treatments owing to the large number of complications, including wound infection, postoperative pain, and consecutive resurgeries. One of the main drawbacks is the constant pressure acting on the hollow organ. The natural counterpart, however, adapts to external factors such as climbing stairs or resting in bed, so that the function is guaranteed and the tissue can regenerate. Hence, sensor-controlled devices with the necessary time response have to be developed [16]. As dielectric elastomer actuators (*.xhtml) not only provide the necessary forces, strains, and response time but can also simultaneously be operated as sensors, these artificial muscles have a huge potential to become the basis of future active implants [17]. There are, however, several challenges to be solved, mainly related to the high voltages required to drive micrometer-thin DEA. Sandwiched nanometer-thin elastomer films with ultrathin compliant electrodes have to be made available to fabricate biomimetic artificial sphincters and finally to successfully treat incontinence.
The book Nanotechnology for Human Health should promote the prosperous use of nanotechnology in prevention, diagnosis, and therapy of the most relevant diseases of our century. It should comparably become a tool for research-interested medical doctors as well as natural scientists and engineers with a strong affinity to support curing patients [18,19]. In this manner, patients concerned will benefit from this collaborative initiative of an interdisciplinary team of researchers.
References
1
Lloyd-Jones, D., Adams, R., Carnethon, M., Simone, G.D., Ferguson, T.B., Flegal, K., Ford, E., Furie, K., Go, A., Greenlund, K., Haase, N., Hailpern, S., Ho, M., Howard, V., Kissela, B., Kittner, S., Lackland, D., Lisabeth, L., Marelli, A., McDermott, M., Meigs, J., Mozaffarian, D., Nichol, G., O'Donnell, C., Roger, V., Rosamond, W., Sacco, R., Sorlie, P., Stafford, R., Steinberger, J., Thom, T., Wasserthiel-Smoller, S., Wong, N., Wylie-Rosett, J., and Hong, Y. (2009) Heart disease and stroke statistics – 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.
Circulation
,
119
(3), e21–e181.
2
Holme, M.N., Fedotenko, I.A., Abegg, D., Althaus, J., Babel, L., Favarger, F., Reiter, R., Tanasescu, R., Zaffalon, P.-L., Ziegler, A., Müller, B., Saxer, T., and Zumbuehl, A. (2012) Shear-stress sensitive lenticular vesicles for targeted drug delivery.
Nat. Nanotechnol.
,
7
(8), 536–543.
3
Korin, N., Kanapathipillai, M., Matthews, B.D., Crescente, M., Brill, A., Mammoto, T., Ghosh, K., Jurek, S., Bencherif, S.A., Bhatta, D., Coskun, A.U., Feldman, C.L., Wagner, D.D., and Ingber, D.E. (2012) Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels.
Supramol. Sci.
,
337
(6095), 738–742.
4
Saxer, T., Zumbuehl, A., and Müller, B. (2013) The use of shear stress for targeted drug delivery.
Cardiovasc. Res.
,
99
, 328–333.
5
Marcenes, W., Kassebaum, N.J., Bernabé, E., Flaxman, A., Naghavi, M., Lopez, A., and Murray, C.J.L. (2013) Global burden of oral conditions in 1990–2010: a systematic analysis.
J. Dent. Res.
,
92
(7), 592–597.
6
Petersen, P.E. (2008) World Health Organization global policy for improvement of oral health: World Health Assembly 2007.
Int. Dent. J.
,
58
(3), 115–121.
7
Petersen, P.E. (2009) Global policy for improvement of oral health in the 21st century: implications to oral health research of World Health Assembly 2007, World Health Organization.
Community Dent. Oral Epidemiol.
,
37
(1), 1–8.
8
Deyhle, H., Bunk, O., Buser, S., Krastl, G., Zitzmann, N., Ilgenstein, B., Beckmann, F., Pfeiffer, F., Weiger, R., and Müller, B. (2009) Bio-inspired dental fillings.
Proc. SPIE
,
7401
, 74010E.
9
Deyhle, H., Bunk, O., and Müller, B. (2011) Nanostructure of healthy and caries-affected human teeth.
Nanomedicine
,
7
(6), 694–701.
10
Gaiser, S., Deyhle, H., Bunk, O., White, S.N., and Müller, B. (2012) Understanding nano-anatomy of healthy and carious human teeth: a prerequisite for nanodentistry.
Biointerphases
,
7
(4), 14.
11
Curtis, A. and Wilkinson, C. (1999) New depths in cell behaviour: reactions of cells to nanotopography.
Biochem. Soc. Symp.
,
65
, 15–26.
12
Müller, B. (2001) Natural formation of nanostructures: from fundamentals in metal heteroepitaxy to applications in optics and biomaterials sciences.
Surf. Rev. Lett.
,
8
(1 and 2), 169–228.
13
Müller, B., Riedel, M., Michel, R., De Paul, S.M., Hofer, R., Heger, D., and Grutzmacher, D. (2001) Impact of nanometer-scale roughness on contact-angle hysteresis and globulin adsorption.
J. Vac. Sci. Technol. B
,
19
(5), 1715–1720.
14
Althaus, J., Padeste, C., Köser, J., Pieles, U., Peters, K., and Müller, B. (2012) Nanostructuring polyetheretherketone for medical implants.
Eur. J. Nanomed.
,
4
(1), 7–15.
15
Althaus, J., Urwyler, P., Padeste, C., Heuberger, R., Deyhle, H., Schift, H., Gobrecht, J., Pieles, U., Scharnweber, D., Peters, K., and Müller, B. (2012) Micro- and nanostructured polymer substrates for biomedical applications.
Proc. SPIE
,
8339
, 83390Q.
16
Fattorini, E., Brusa, T., Gingert, C., Hieber, S.E., Leung, V., Osmani, B., Dominietto, M.D., Büchler, P., Hetzer, F., and Müller, B. (2016) Artificial muscle devices: Innovations and prospects for fecal incontinence treatment.
Ann. Biomed Engin.
,
44
, 1355–1369.
17
Müller, B., Deyhle, H., Mushkolaj, S., and Wieland, M. (2009) The challenges in artificial muscle research to treat incontinence.
Swiss Med. Wkly.
,
139
(41–42), 591–595.
18
Müller, B., Zumbuehl, A., Walter, M.A., Pfohl, T., Cattin, P.C., Huwyler, J., and Hieber, S.E. (2015)
Translational Medicine: Nanoscience and Nanotechnology to Improve Patient Care
, Wiley-VCH Verlag GmbH, Weinheim, p. 15.
19
Müller, B. (2010) Tailoring biocompatibility: benefitting patients.
Mater. Today
,
13
(4), 58.
2Nanoscience and Nanotechnology and the Armory for the Twenty-First Century Health Care
Marcel Van de Voorde1 and Pankaj Vadgama2
1Assembly, Paris, Rue du Rhodania, 5, BRISTOL A, Appartement 31, 3963 Crans-Montana, Switzerland
2Queen Mary University, Centre for Materials Research, Mile end Road, London E1 4NS, UK
2.1 Conceptual Dream
The discovery of atomic structure in solids initiated the development of man-made materials and now allows us to exquisite control over their properties and functions. Similarly, our understanding of molecular and chemical processes has allowed us to better understand and predict chemical reactions. Perhaps, the seminal moment came with Feynman's lecture to the American Physical Society in 1959: “There is plenty of room at the bottom.” The prospects for uptake of the nanoscale paradigm in medicine have galvanized interest, both in academia and industry [1–10].
2.2 A Real World Encounter
Accelerating advances encompassing the nanoscale have enabled us to design therapeutic agents with ever-increased likelihood of clinical effectiveness [2] and our understanding of the pathophysiology of disease has also been enhanced. In the context of cell and tissue organization, such knowledge, coupled with our understanding of macro- and microanatomy has opened a path to the emerging field of nanoanatomy. Our newly found nanodomain bridges the gap between the molecular and the “macro,” and it will be of crucial importance in the future, given that biology uses supramolecular entities, that is, nanostructures, as key engines of control and management of the cellular world [11,12]. With better understanding of the nanoscale we will be better equipped to create nanomaterials to augment our current armory of diagnostic and therapeutic systems. Furthermore, a thorough structural characterization of the subcellular/supramolecular will give us considerably greater mechanistic understanding. This will have an impact on internal medicine, but is already seeing application in cardiovascular and regenerative medicine along with a broader refining of targeted therapies. Structure–function relationships at the nanoscale also has huge implications for complex biomimetics, for example, in the reproduction of multifunction sensing and organ systems to hard tissue design in dentistry and orthopedics [2,13].
2.3 Mapping the Microcosm of Disease
Nanomedicine delivers nanotechnology and nanoscience to practical health care with unprecedented precision. It exploits the often improved, and often unexpected physical, chemical, and biological properties of materials at this extreme length scale. Here, man-made structures match the length scale of many natural functional units in living organisms, allowing scale-matched interactions [2,14].
As the population ages, in developed nations, and those in developing countries become more subject to environmental threats and infectious agents, medicine is confronted with exceptional health care challenges. Early diagnosis and therapy is now of vital importance [15].
By building up strength in nanoscience and nanotechnology, early disease detection, preventative measures, and targeted therapies can be developed that will benefit all mankind.
2.4 Delivery at the Clinical “Coal Face”
The immediate practical outcome will be to complement, and indeed augment, existing therapies [1,16–18]. Nowhere is this more obvious than in the tailoring of therapeutic carriers to deliver antibiotics in innovative ways to increasingly resistant microorganisms. In this way, many antibiotic agents that are currently considered to be coming to the end of their useful lifetimes could see resurgent use, reducing the demand for expensive de novo drug development. The quality of life is as important as its longevity, and here also the nanoscale can offer solutions. With failing cellular and tissue structures, it may be possible to supply nanoscale substitutes in the way that traditional biomaterials are being used for macrostructures [19,20]. Thus, while say an osteoporotic fracture is seen as a macroscale failure, in reality it is a failure of organization at the nanoscale, and is therefore amenable to management at this scale.
2.5 A High Precision Aim for Disease Targets
Scientific discoveries in nanomedicine will have to pass through time-consuming development stages, including preclinical and clinical studies, to reach commercialization. However, reengineered agents are emerging and have been targeted variously to cancer treatment, hepatitis and other infectious diseases, anesthesia, cardiac/vascular disorders, inflammatory and immune disorders, endocrine and exocrine disorders, degenerative disorders, and so on [1,4,21–25]. Perhaps the major part of current research effort is focused on cancer treatment. We now have high-impact interventions built on nanoscale medicines and nanocarriers. Preliminary exploitation was applied to imaging agents and now targeting of drugs and even remotely trackable agents is becoming feasible [18,26–28].
2.6 A Materials Revolution for Clinical Care
Earlier research, developed model systems, laid the foundation for nano materials and showed the potential for revolutionizing medicine. Preliminary evidence was provided of reconfigured bulk and surface properties afforded by nanostructures and how these could be harnessed for better ways of detecting and managing diseases, and in some cases even preventing them. In parallel, manipulative and analytical tools have been devised that offer the underpinning infrastructure. These addressing the unique imaging, manipulation, and interrogation needs of such materials [29–31]. The same, of course, applies to their natural biological counterparts. The scene is set to apply our knowhow to advance soft nano-objects based around proteins and other biopolymers. Through this strategy we may also have a better understanding of how biology achieves supramolecular systems. We certainly have a fix on structure, such as that of the elegant ribosomal machine (Nobel Prize Chemistry, 2009), and a full functional understanding may come within reach. An extreme challenge would be how chromosomal DNA is exposed and read in real time [32].
Artificial nanostructures able to interfere with such complex, self-assembly nanosystems may allow for the manipulation of these processes to deliver therapeutic outcomes, for example, via gene silencing and gene amplification. Without experimentally interacting with biology at the nanoscale in the first place, we will not be able to understand this all important nanobiology realm.
A combination of advanced tailored nanomaterials and monitoring tools will provide us with closer information on the dynamics of nano–bio interactions. We are well placed to delve into even the most elusive of natural nanostructures [33,34]. A practical advance could be a reinvention of the current surgery paradigm, where selective addition and removal of components at the cellular level are affected. A potent exemplar is in neurointervention, where techniques for neuronal repair and nano scaffolds for axonal growth already seem feasible for clinical use. Future extended neuronal lifespan and control of nanoaggregate formation may provide resolution of age-related neurodegenerative disease, most notably dementia.
2.7 Robotics for Microrepair and Healing
Future possibilities lie in the use of so-called nanorobots introduced through the vascular system but having the capability of reaching a specific cell type to undertake a preset surgical maneuver [35,36]. Already femtosecond lasers perform 100 nm incisions in eye surgery and in regard to materials we have hemostasis peptides that can self-assemble as nanoscale protective barriers for sealing up wounds.
Cross-referencing of the diseased and normal at the nanoscale will also provide deeper insights. This text provides some representative examples of nanotechnology-based tools, materials, and systems that are set to have an impact on both biology and medicine.
2.8 A Dialog with Cells
Our ability to transport materials to the cell is essentially a function of length scale [37,38]. Nanoscale devices might be developed to achieve this for us automatically. While being a hundred or thousand times smaller than a cell and on a par with biomacromolecules such as enzymes and cell receptors, they might have a built-in smartness that allows targeting and recognition. The scales for such machines are already evident with sophisticated, interactive structures such as hemoglobin at 5 nm, DNA 2.5 nm, and quantum dots 10 nm. In principle, a nanostructure of 50 nm size could enter the cell, and one of 20 nm size could traverse a capillary bed. Surface charge, shape, and polarity will modulate these properties. For the innovative nanoengineer, a combination of surface design, bulk reactivity, and payload release are all open for massive exploitation and development. Viruses already achieve such desired combinations, with their unique negotiation of cell receptors. A progression of this natural technology to achieve the same with artificial constructs would pay major dividends without the health risks. Gene therapy, for example, need not take the risky route of natural viral carriers.
Nanolayers might be usable for masking or protection of cellular surfaces such as vascular endothelial cells in order to manipulate vascular access. Masking, however, is a far greater challenge for the artificial particle introduced into the body, susceptible to all that the body can throw at it by way of masking and rejection with inevitable loss of efficacy.
The payoff of targeted therapy is a huge one. There is now major analysis of cancer/patient genomes to tailor therapeutic agents for individual patients. Anything that diminishes toxic drug effects while maintaining potency is a magnet for research, also presenting is a distinct opportunity for big pharma to advance our drugs concepts.
2.9 Stealth Materials for a More Potent Delivery
Nanostructures to package proteins and other biodegradable agents could be given orally as opposed to the intravenous or tissue injection route. Complex nanoengineering is required to both protect such agents from degradation and make them available for intestinal uptake and onward transmission. The dual need is for protection against chemical defense while allowing for effective penetration of physical barriers. The barrier problem is at its most extreme at the blood–brain barrier and intact skin. Assistive technologies such as electroporation and electrical fields gradients are showing great promise, for example, for melanoma, and with a nanotechnology synergy the effects will surely be dramatic. Beyond this surely there may be the opportunity to fine-tune delivery to reach specific subcellular, including nuclear, subcomponents. At close range weak magnetic and dielectric properties might well serve as strong field manipulative tools. The challenge is the design. Magnetic liposomes and binary shell polyferrofluids have already provided better particle loading and tissue localization through external magnetic fields [24,26,39].
In an era where the drug pipeline is no longer guaranteed, a standard drug injected into tissue or given intravenously can be made to profoundly alter its pharmacodynamics without any change in chemistry, simply by associating it with a nanocarrier. So, there are likely to be drug advances made without the need for always discovering completely new therapeutic agents. Beyond and major cost savings in drug development would be a timely development when we need so many antimicrobials to fit for an era of resistant superorganisms.
The vascular compartment is itself a disease focus. The high incidence of cardiovascular disease has profound healthcare implications [6]. Thus, carrier nanoparticles for dealing with atherosclerotic plaques and inflammatory cardiovascular disease would revolutionize cardiac medicine. Heart tissue regeneration via nano particles, for example, releasing tissue regenerative agents just where they are needed could pay the way for treating more dramatic diseases such as myocardial infarction and stroke.
2.10 Improved Biointerrogation for a Better Understanding
Many diseases, including cancer, originate from mutations with alterations in cellular regulatory and metabolic pathways. Early sensitive diagnosis has been constrained by the lack of biosensors and probes capable of reaching the local diseased compartment as opposed to, say, the signals coming from that zone, such as circulating biomarkers. Nanomaterials interacting with specific intracellular signals with some form of optical, magnetic, or electrical relays could provide early alert for disease [26,35]. In this context, in vivo nanodiagnostics will be a major challenge combining the need for device biocompatibility with the IT element of remote interrogation. Loaded nanoparticles with an indicator function offer some glimpse of what is possible here. Extension of this concept to the intact organism or tissue would be a further, major step forward.
The greater emphasis on point-of-care and self-testing for rapid and early diagnosis also means the diagnostics have to be operationally simple. There is also a premium on multiparameter testing. Using nanostructures and nanosensing surfaces allows for a sensing system that has exceptional redundancy, providing robust and fast results. A true “lab-on-a-chip” could be realized using nanoscale sample handling, and coupling with extreme miniaturization of optical, electrochemical, and other platforms becomes feasible [2,40]. The patient then becomes empowered to track their own health status. A further attribute of nanotechnology would be the provision of nanoporous membrane structures for scaling down of surface interaction, down to the molecular level. Nanoporous liquid membranes are already under development for DNA sequence identification.
Nanoendoscopy is a further diagnostic method that has its precursor in the Pill Cam capsule endoscope. Here, peristaltic movement of a videocamera capsule down the gut yields intermittent imaging of the small intestine. A pill-sized camera with nanocomponents could be used to replace existing, more invasive, colonoscopy.
The key strength of nanodevices for sensing is their nonintrusive nature. This has the added advantage of provoking less biorejection, avoiding tissue disruption in the patient. Again, disease alerts could be provided earlier, for example, for those with coronary artery disease to ensure that the cardiac cells are not under hypoxic stress or in glaucoma through real time intraocular pressure monitoring with a contact system. In the case of both the central and peripheral nervous system, nanoneuroprostheses might well be designed for intelligent functional electrical stimulation (FES) with high spatial resolution.
Nanotechnology could accelerate the move away from laboratory testing. At the wider societal level the nonintrusiveness could allow use in medical surveillance for preventative medicine in whole populations.
2.11 Crossing the Structure–Function Threshold
Structural and functional imaging such as PET is advancing, but there is an even greater need for better spatial resolution to image intralesion heterogeneity, tissue viability, and delineation of disease margins. Nanostructures, here as imaging beacons, offer huge advantages [7,26]. Already, superparamagnetic particles have been used to effect imaging, but such systems able to respond to local chemistry could create a revolution in functional imaging. While complex and potentially expensive, better disease management would bring down overall health care costs. Recent progress in multifunctional contrast agents using compounds responsive to biological activity suggests the capability is on the horizon.
2.12 Living Implants for a Living Matrix
Traditional implant materials have made major headway in therapy. Their limited surface bio/hemocompatibility, however, compromises their long-term function. Surface nanostructuring and triggering of desirable, as opposed to adverse tissue/blood responses, could radically change the device, and patient's, lifetime. Such design could include chemical functionalization with the presentation of sophisticated motifs and subtle types of environmental responsiveness and remodeling [10,14,41]. Cells react to both surface chemistry and topography, so engineering of such nanomotifs has decided advantages. In dentistry, dental implants with nanostructured surfaces might enhance osteoblast adhesion, esthetic presentation, and provide for on-going drug release and treatment of periodontal disease.
Tissue engineering uses artificial scaffolds to direct and differentiate cells. With nanoscale fibers, pores, and decoration, spatial organization and differentiation would enter a quite unprecedented order of control [2,42]. Eventual tissue mimicry is possible, not just of homogeneous tissue such as cartilage, but of the refined mesoarchitecture of large organs. Parallel developments in stem cell research will provide previously unimaginated types of cell composite, with more elegant nanoarchitectures now able to engineer the local cell environment for high precision cellular cues for differentiation.
2.13 Taming the Nanointerface
The properties that make nanomaterials so attractive may also make them hazardous to cells and tissues [38]. Concerns have been raised about unintentional health and environmental impacts. For instance, metal oxide-based nanoparticles (TiO2, ZnO, Fe3O4, Al2O3, and Cr2O3) and quantum dots have a core made up of relatively toxic metals (Cd, Se, etc.). So nontoxic analogues are a vital next step. This again brings in the fundamentals of materials science. Particle residence times in the human body, may also be a factor, so it will be necessary to be clear, as with standard drug agents, as to the pathways taken by nanomaterials in the body over time: how they accumulate, break-down and are excreted, and the degree to which they cause oxidative stress to the tissues that they contact.
The bystander effect relates to the widening action of radiation on tissues through cell signaling. Nanobeams, targeting individual organelles of a cell have been useful tools for studying such communication and also trigger mechanisms, for example, for DNA. While nanoparticles could also be used in an analogous way, this also highlights their potency and potential for causing damage if not properly designed.
Metal ions play a role in cell regulatory processes but can also provoke disease states through deficiency or excess. They are known to play a part in some cancers and in neurodegenerative disease like Alzheimer's. Therefore, where nanoscale metallized components are in cell contact, it becomes necessary to understand the dynamics of ion release and microenvironmental effects. In parallel, agents for ion removal may allow therapeutic modulation where ion release is for therapeutic purposes.
The effect of nanostructures on the aggregation of fibrous proteins such as amyloid may also be of importance. Not only might they promote neurodegeneration pathways, but also a better understanding of aggregation processes may emerge of natural peptides and mitigation strategies may be of value for the design of selforganized structures for therapies [27].
2.14 Where are We Now?
Over the past decade, nanomedicine and nanobiology have undergone radical transformation from fantasy to real science. The days of discussing advances in this area in the context of nanobots are over, and systems and nanomaterials have emerged that provide realistic analytical and therapeutic advantages over conventional approaches. We now know that much of biology is executed at the nanoscale, but our understanding resides at the extreme molecular and macro levels. Nanostructures used alone, or coupled with active payloads, along with advanced manipulative tools are the missing bridge between these two worlds. We are moving from just creating nanostructures to a systems approach where the nanostructures are spatially positioned. The potential aim of this 3D organization is to mimic environments that can be seen as natural by tissue, and through this to accelerate replacement and repair [41]. At the other extreme, we are learning to design nanostructures that can survive and operate under hostile in vivo conditions.
Some of the foundations have been led to nanostructured scaffolds for the growth of human dermal fibroblasts, for example, for chronic diabetic wounds and burns, nanosilver-loaded wound dressings for broad-spectrum antimicrobial action, image enhancers in radiology. Associated analytical tools for imaging and manipulation of both particles and biological structures are now advanced in ways that would have been viewed as science fiction a few years ago.
In the next phase of development, we need to unravel the complexities of the biointeractions and through this to translate a technological revolution from the laboratory to the patient.
2.15 Where will the Revolution Take Us?
Innovations are likely to shift toward those associated with overall systems and their applications. It is this shift that will impact on medicine. We will see uses in both general medicine and surgery. Increasing attention will be toward complex functional replacement of tissues that are either not capable of regeneration or that have sophisticated structures involving multiple cell types. Such structures have to be spatially and functionally integrated in a way that does not oversimplify what we have in the natural tissue. The use of nanoarchitectures will progressively reduce the need for artificial macrostructures and emphasis materials at the nanoscale. The latter should also allow for greater convergence of diverse material types into a single monolithic entity. In cancer, we need to identify tumor margins, micrometastases, and the residuum of tumor burden to a higher level of sensitivity than is currently possible. In tissue engineering, we need nanomaterials as the extracellular chaperone for cell guidance, a kind of artificial extracellular matrix. We need to learn the relation between natural healing and regeneration and the artificial nanophases we will create, answering such questions as material degradation rates, surface adsorption/adhesion, and nutrient transport and its anisotropy. Nanocarrier-aided targeted delivery will need to be designed in a way that losses in the reticuloendothelial system are not so great as to make therapy ineffective. This brings nanoscience into mainstream biology and the processes of phagocytosis and particle membrane interactions. Cardiovascular science may well show the earliest advances with nanofiber-based scaffolds for vascular grafts, nanostructured drug-eluting stents, and thromboresistive surfaces.
A key justification is that nanotechnology will aid doctors to address currently unsolvable problems, for example, sight-restoration in retinal degenerative disease. In dentistry, orthodontic manipulative nanostructures could manipulate periodontal tissues, and even the use of nanotechnology-based drug release agents could degrade organic compounds into harmless odorless structures and also break down calculi.
Despite the ultimate value of in vivo monitoring with nonintrusive nanostructures, the more accessible, and rapid advances are likely to be seen in in vitro diagnostics. In vivo toxicity is not a concern here and the diagnostic industry is capable of building on existing platforms. Improved diagnostics, lower cost, and a reduced materials burden will widen uptake and act as a further vehicle for stratified medicine.
All of the above will need to combine engineering advances with strategies for handling the biological environment, both for the benefit of the nanostructure and the host environment. To facilitate this, it will be necessary to implement alternative manufacturing approaches. New products, however, will need to address stringent safety and environmental compatibility standards. The more potent the action, the more likely is the undesirable effect. Lifecycle outcomes will also need to be addressed: nanoparticle use means a greater surface activity and subsequent impact on the environment, making it paramount to develop appropriate destruction and disposal capabilities in parallel.
2.16 Conclusions
Our understanding of the molecular world with regards to medicine has seen an astonishing development. Through this development we recognize that the spatial orientation and arrangement of this world is also important. Biology is chiral, directional, spatially alert, and embodies complex anisotropies. The supramolecular domain represents the stuff of nanomedicine with the emerging understanding of the solid states. We are now on the threshold of converging the formalism of solid-state physics with soft matter. This is not just a scientific refinement but a potential scientific revolution. There are practical implications for our greater understanding of disease states and through this a better design of therapeutic agents.
A medical future without nanotechnology would have a reduced toolkit to tackle intractable conditions. Hospitals will not sustain the even escalating success of the past without the input from new methodologies. Nanotechnology offers readily available solutions. It may be that traditional specialties will undergo a refinement with the advent of nanotherapeutics. Without the nanoinput, imaging and diagnostics would not keep pace with the escalating need for high structural resolution and sensitivity. This quality of diagnostic tools is indispensable, if we are to tackle disease at the earliest stage and to identify aberrations that allow for preventative steps – the target of population preventative medicine. Degenerative conditions, associated with the aging population, especially, will remain only partially manageable. Modern medicine will initially apply nanoconstructs and nanoparticles to Cinderella areas where no alternative exists but with improved engineering of materials the scope will widen. Any extension, however, needs also to take into account a wider societal and cultural stance on nanotechnologies, which if not succeeding will create a resistance to uptake to the detriment of those who need the technology the most. This is where beyond the science arena societal engagement will be vital and objective assessments vital as with any trial data used to move to new treatments in the evidence-based way. A clue to the future comes from our past and the way we have accommodated the toxic and damaging part of radiology, radiotherapy, and therapeutics in order to benefit from their benefits. The nanotechnology will make no difference. As a label nanotechnology has been highly beneficial in our better understanding of matter, but the message now to government and funders should be that of funding nanotechnology not as an isolated entity, but as a vital bridge between the molecular and structural that will help better understand our external and internal environment.
This book with the selected topics on nanomedicine will fuel the creativity of medical doctors, natural scientists, and engineers in analyzing the human body and developing nanotechnology-based treatments to improve human health.
References
1
Aleassa, E.M., Xing, M., and Keijzer, R. (2015) Nanomedicine as an innovative therapeutic strategy for pediatric cancer.
Pediatr. Surg. Int.
,
31
(7), 611–616.
2
Jesion, I., Skibniewski, M., Skibniewska, E., Strupinski, W., Szulc-Dabrowska, L., Krajewska, A., Pasternak, I., Kowalczyk, P., and Pinkowski, R. (2015) Graphene and carbon nanocompounds: biofunctionalization and applications in tissue engineering.
Biotechnol. Biotec. Eq.
,
29
(3), 415–422.
3
Pelipenko, J., Kocbek, P., and Kristl, J. (2015) Critical attributes of nanofibers: preparation, drug loading, and tissue regeneration.
Int. J. Pharm.
,
484
(1–2), 57–74.
4
Gregori, M., Masserini, M., and Mancini, S. (2015) Nanomedicine for the treatment of Alzheimer's disease.
Nanomedicine
,
10
(7), 1203–1218.
5
Peer, D., Karp, J.M., Hong, S.P.
et al.
(2007) Nanocarriers as an emerging platform for cancer therapy.
Nat. Nanotechnol.
,
2
(12), 751–760.
6
Bawarski, W.E., Chidlowsky, E., Bharali, D.J.
et al.
(2008) Emerging nanopharmaceuticals.
Nanomed. Nanotech. Biol. Med.
,
4
(4), 273–282.
7
Kingsley, J.D., Dou, H., Morehead, J.
et al.
(2006) Nanotechnology: a focus on nanoparticles as a drug delivery system.
J. Neuroimmune Pharmacol.
,
1
(3), 340–350.
8
Pison, U., Welte, T., Giersig, M.
et al.
(2006) Nanomedicine for respiratory diseases.
Eur. J. Pharmacol.
,
533
(1–3), 341–350.
9
Freitas, R.A. (1999)
Nanomedicine
, Volume I: Basic Capabilities, CRC Press, ISBN-13: 978-1570596803 ISBN-10: 1570596808.
10
Webster, T. (ed.) (2012)
Nanomedicine
, Woodhead PublishingPrint Book, ISBN: 97808570.
11
Baharvand, H. (2015)
Stem Cell Nanoengineering
, Wiley-Blackwell, ISBN: 978-1-118-54061-9, 432 p.
12
Milane, L., Trivedi, M., Singh, A., Talekar, M., and Amiji, M. (2015) Mitochondrial biology, targets, and drug delivery.
J. Control. Release
,
207
, 40–58.
13
Jain, K.K. (2008)
The Handbook of Nanomedicine
, Springer, ISBN: 978-1-603-27318-3.
14
Ruiz-Molina, D., Novio, F., Roscini, C., and Mano, J.F. (2014)
Bio- and Bioinspired Nanomaterials
, Wiley-VCH Verlag GmbH & Co. KGaA, ISBN: 978-3-527-33581-7.
15
Prasad, P.N. (2012)
Introduction to Nanomedicine and Nanobioengineering
, John Wiley & Sons, Inc., ISBN 978-1-118-09343-6, 608 p.
16
Li, J., Wang, Y., Liang, R.
et al.
(2015) Recent advances in targeted nanoparticles drug delivery to melanoma.
Nanomed. Nanotech. Biol. Med.
,
11
(3), 769–794.
17
Nguyen-Ngoc, T. and Raymond, E. (2015) Reinvention of chemotherapy: drug conjugates and nanoparticles.
Curr. Opin. Oncol.
,
27
(3), 232–242.
18
Mura, S., Bui, D.T., Couvreur, P., and Nicolas, J. (2015) Lipid prodrug nanocarriers in cancer therapy.
J. Control. Release
,
208
, 25–41.
19
Ding, H.M. and Ma, Y.Q. (2015) Theoretical and computational investigations of nanoparticle-biomembrane interactions in cellular delivery.
Small
,
11
(9–10), 1055–1071.
20
Lee, W.H., Loo, C.Y., Traini, D., and Young, P.M. (2015) Nano- and micro-based inhaled drug delivery systems for targeting alveolar macrophages.
Expert Opin. Drug Deliv.
,
12
(6), 1009–1026.
21
Medintz, I.L., Uyeda, H.T., Goldman, E.R.
et al.
(2005) Quantum dot bioconjugates for imaging, labelling and sensing.
Nat. Mater.
,
4
(6), 435–446.
22
Kesharwani, P. and Lyer, A.K. (2015) Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery.
Drug Discov. Today
,
20
(5), 536–547.
23
