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ROB BURGESS<br />
UNDERSTANDING<br />
NANOMEDICINE<br />
An Introductory Textbook
Published by<br />
<strong>Pan</strong> <strong>Stanford</strong> <strong>Publishing</strong> Pte. Ltd.<br />
Penthouse Level, Suntec Tower 3<br />
8 Temasek Boulevard<br />
Singapore 038988<br />
Email: editorial@panstanford.com<br />
Web: www.panstanford.com<br />
British Library Cataloguing-in-Publication Data<br />
A catalogue record for this book is available from the British Library.<br />
Understanding Nanomedicine: An Introductory Textbook<br />
Copyright © 2012 <strong>Pan</strong> <strong>Stanford</strong> <strong>Publishing</strong> Pte. Ltd.<br />
All rights reserved. This book, or parts thereof, may not be reproduced in any form<br />
or by any means, electronic or mechanical, including photocopying, recording or<br />
any information storage and retrieval system now known or to be invented, without<br />
written permission from the publisher.<br />
For photocopying of material in this volume, please pay a copying fee through<br />
the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923,<br />
USA. In this case permission to photocopy is not required from the publisher.<br />
Cover art courtesy of United Therapeutics Corporation, The Unither Nanomedical<br />
& Telemedical Technology Conference and Christine Charboneau<br />
ISBN 978-981-4316-38-5 (Hardcover)<br />
ISBN 978-981-4303-52-1 (eBook)<br />
Printed in the USA
To<br />
my wife, Jane,<br />
daughter, Zoie,<br />
mother, Lola, and<br />
father, Bob
Contents<br />
Acknowledgment<br />
Preface to the Professor<br />
Preface to the Student<br />
Reviewers<br />
xix<br />
xxi<br />
xxvii<br />
xxix<br />
1 Fundamentals of Nanotechnology 1–44<br />
Nanotechnology and Its Origins 1<br />
The Basics of the Nanoscale 5<br />
Nanomaterials and Nanoparticles 7<br />
Fullerenes 7<br />
Single-Walled Carbon Nanotubes (SWNT) 12<br />
Multi-Walled Carbon Nanotubes (MWNT) 14<br />
Thermal Properties of Carbon Nanotubes 15<br />
Absorptive Properties of Carbon Nanotubes 16<br />
Perfluorocarbons 18<br />
Inorganic Nanoparticles 18<br />
Types of Biocompatible Inorganic Metal Nanoparticles 19<br />
Gold Nanoshells 19
viii<br />
CONTENTS<br />
Superparamagnetic Nanoparticles 21<br />
Silver Nanoparticles 22<br />
Other Types of Biocompatible Nanoparticles 23<br />
Dendrimers 23<br />
Micelles and Liposomes 24<br />
Nanotools 27<br />
Scanning Tunneling Microscope 27<br />
Atomic Force Microscope 29<br />
Commercial Nanotools: The nProber TM 30<br />
Current Manufacturing Research 32<br />
Top-Down Approach 33<br />
Bottom-Up Approach 33<br />
Atomically Precise Manufacturing 35<br />
Bionanotechnology 36<br />
Nucleic Acid Nanotechnology 36<br />
Nanotechnology’s Potential Impact on Medicine 38<br />
Chapter Summary 41<br />
Nanotechnology and Its Origins 41<br />
The Basics of the Nanoscale 41<br />
Nanomaterials and Nanoparticles 41<br />
Nanotools 42<br />
Current Manufacturing Research 42<br />
Bionanotechnology 42<br />
Key Terms 43<br />
Review Questions 44<br />
2 Nanoparticles and Hyperthermic Cancer<br />
Therapeutics 45–75<br />
Nanoparticles and Thermal Ablation 45<br />
Mechanisms of Action 45<br />
Metals and Light 46<br />
Metals and Radiofrequency Waves 46
CONTENTS ix<br />
Carbon Nanotubes and Radiofrequency Waves 47<br />
Carbon Nanotubes and Light 49<br />
Carbon Nanotubes, Heat and Cancer Therapeutics 50<br />
Superparamagnetic Nanoparticles, Magnetism<br />
and Mechanism of Action 51<br />
Treatable Types of Cancer 53<br />
Non-specific, Localized Use of Nanoparticles<br />
for Tumor Ablation 54<br />
Targeting Nanoparticles to Specific Sites for Tumor Ablation 54<br />
Targeting Agents 56<br />
Monoclonal Antibodies 56<br />
Small Molecules 59<br />
Aptamers 63<br />
Peptides 65<br />
Targeting Moiety Attachment 66<br />
Covalent Attachment 66<br />
Non-covalent Attachment 68<br />
In vivo Anticancer Platform Delivery 71<br />
Localized Injection 71<br />
Intravenous Injection 71<br />
Chapter Summary 73<br />
Nanoparticles and Thermal Ablation 73<br />
Non-specific, Localized Use of Nanoparticles for<br />
Tumor Ablation 73<br />
Targeting Nanoparticles to Specific Sites for Tumor Ablation 73<br />
In vivo Anticancer Platform Delivery 74<br />
Key Terms 74<br />
Review Questions 75<br />
3 Nanofiber-Based Scaffolds and Tissue Engineering 77–116<br />
Composition and Types of Nanofibers 78<br />
Natural Polymeric Nanofibers 79<br />
Collagen 79
x<br />
CONTENTS<br />
Chitosan 81<br />
Hyaluronic Acid (HA) 81<br />
Gelatin 82<br />
Silk Fibroin 83<br />
Human Protein 84<br />
Synthetic Polymeric Nanofibers 87<br />
Poly(lactic-co-glycolic acid) (PLGA) 89<br />
Synthetic Non-polymeric Nanofibers 91<br />
Carbon Nanofibers 91<br />
Techniques for the Synthesis of Nanofibers 93<br />
Electrospinning 93<br />
Self-Assembly 95<br />
Phase Separation 98<br />
Nanofiber Applications in Tissue Engineering 100<br />
Bone, Cartilage and Ligaments 100<br />
Skin 105<br />
Vasculature 106<br />
Nanofiber Applications in Controlled Drug Delivery 110<br />
Chapter Summary 113<br />
Composition and Types of Nanofibers 113<br />
Techniques for the Synthesis of Nanofibers 114<br />
Nanofiber Applications in Tissue Engineering 114<br />
Nanofiber Applications in Controlled Drug Delivery 114<br />
Key Terms 115<br />
Review Questions 115<br />
4 Nanotechnology and Neuroscience 117–154<br />
Nanomaterial Scaffolds and Neuroregeneration 118<br />
Carbon Nanotube-Based Neuronal Matrices 121<br />
Neuronal Nanotube Matrices from Other Materials 125<br />
Nanomaterials for Crossing the Blood/Brain Barrier 125<br />
Micelles 128
CONTENTS xi<br />
Liposomes 130<br />
Dendrimers 131<br />
Nanoparticles 136<br />
Nanogels 139<br />
Nanomaterials and Neuroprotection 143<br />
Nanoparticle-Based Oxides (Anti-Oxidants) 143<br />
Fullerenes 144<br />
Cells as Nanomaterial Carriers for Clinical Neuroscience 147<br />
Chapter Summary 150<br />
Nanomaterial Scaffolds and Neuroregeneration 150<br />
Nanomaterials for Crossing the Blood/Brain Barrier 150<br />
Nanomaterials and Neuroprotection 152<br />
Cells as Nanomaterial Carriers for Clinical Neuroscience 152<br />
Key Terms 152<br />
Review Questions 153<br />
5 Nanotechnology and Surgery 155–196<br />
Implant and Surgical Instrument Design 156<br />
Nanocoatings for Implants 156<br />
Nanomaterial Adsorption and Adhesion 156<br />
Nanostructured Diamond Coatings 159<br />
Nanostructured Hydroxyapatite Coatings 163<br />
Nanostructured Metalloceramic Coatings 166<br />
Nanopolymer Scaffolds 168<br />
Minimizing Surgical Damage 169<br />
Nanopulses 169<br />
Nanocoatings for Surgical Instruments 171<br />
Post-surgical and Other Wound Healing 172<br />
Point of Entry Repair 172<br />
Laser-Assisted Nanosutures 173<br />
Nanofiber-Based Bandages 173<br />
Antisepsis 176
xii<br />
CONTENTS<br />
Antibiotic Nanocoatings 177<br />
Nanosilver 179<br />
Intracellular Nanosurgery 181<br />
Laser-Based Nanosurgery 182<br />
Non-Laser-Based Intracellular Nanosurgery 190<br />
Chapter Summary 192<br />
Implant and Surgical Instrument Design 192<br />
Minimizing Surgical Damage 193<br />
Post-surgical and Other Wound Healing 193<br />
Intracellular Nanosurgery 194<br />
Key Terms 195<br />
Review Questions 196<br />
6 Nanomatrices for Cell Culture 197–232<br />
A Brief History of Tissue (Cell) Culture 198<br />
Types of Cells Cultured 200<br />
Manipulation of Cultured Cells 200<br />
2D or Not 2D 202<br />
3D Cell Culture and the Issues of Scale and Purity 203<br />
Synthetic Nanofiber Scaffolds 205<br />
Polymer-Based 205<br />
Ultra-Web® 205<br />
PLLA-Based 207<br />
Carbon Nanofiber-Based 208<br />
Natural Nanofiber Scaffolds 209<br />
Collagen-Based 210<br />
Silk Fibroin-Based 212<br />
Chitosan-Based 213<br />
Biocomposites 213<br />
Three-Dimensional Self-Assembling Peptides 215<br />
Cellularizing Nanofiber Scaffolds 219<br />
Optimizing Nanoscaffold Architecture for Cellularization 219<br />
Cell Seeding within the Nanomatrix 221
CONTENTS xiii<br />
Other Nanotechnology-Based Cell Culture Systems 224<br />
Titanium-Based Systems 224<br />
Magnetic Nanoparticle-Based Systems 226<br />
Chapter Summary 228<br />
A Brief History of Tissue (Cell) Culture 228<br />
Types of Cells Cultured 229<br />
Manipulation of Cultured Cells 229<br />
2D or Not 2D 229<br />
3D Cell Culture and the Issues of Scale and Purity 229<br />
Synthetic Nanofiber Scaffolds 230<br />
Natural Nanofiber Scaffolds 230<br />
Cellularizing Nanofiber Scaffolds 230<br />
Other Nanotechnology-Based Cell Culture Systems 231<br />
Key Terms 231<br />
Review Questions 232<br />
7 Nanoparticle-Based Drug Delivery 233–280<br />
Targeted Drug Delivery: Basic Principles 234<br />
Active Targeted Drug Delivery 235<br />
Passive Targeted Drug Delivery 237<br />
Nanoparticles for Drug Delivery: Basic Requirements 238<br />
Types of Nanoparticle-Based Systems for Drug Delivery 240<br />
Synthetic Polymer-Based Nanoparticles 240<br />
Polyethylene Glycol (PEG) 240<br />
Poly(D,L-lactic-co-glycolic) Acid (PLGA) 242<br />
Polylactic Acid (PLA) 245<br />
Polycaprolactone (PCL) 247<br />
Polyacrylate (PACA) 249<br />
Dendrimers 252<br />
Synthetic Metal-Based Nanoparticles 257<br />
Iron Oxide 257<br />
Fullerenes 259<br />
Buckyballs (C 60<br />
) 259
xiv<br />
CONTENTS<br />
Buckysomes 260<br />
Carbon Nanotubes (CNTs) 263<br />
Natural Material-Based Nanoparticles 267<br />
Liposomes 267<br />
Liposomal Nanoparticles and Targeting Inflammation 267<br />
Chitosan 269<br />
Gelatin 272<br />
Albumin 275<br />
Chapter Summary 276<br />
Targeted Drug Delivery: Basic Principles 276<br />
Nanoparticles for Drug Delivery: Basic Requirements 277<br />
Types of Nanoparticle-Based Systems for Drug Delivery 277<br />
Key Terms 279<br />
Review Questions 279<br />
8 Nanodiagnostics 281–225<br />
In vitro Nanodiagnostics 282<br />
Nanobiochips and Nanobiosensors 282<br />
Cantilever Biosensors 295<br />
Nanolaser Scanning Confocal Spectroscopy 296<br />
Mass Spectroscopy and Nanoproteomics 299<br />
Surface-Enhanced Raman Scattering Nanobiosensors 300<br />
In vivo Nanodiagnostics 304<br />
Gold Nanoparticles 304<br />
“Golden” Carbon Nanotubes 306<br />
Magnetic Nanoparticles 307<br />
Perfluorocarbons 310<br />
Quantum Dots 312<br />
Liposomes and Micelles as Diagnostic Metal<br />
Nanoparticle Carriers 315<br />
Chapter Summary 320<br />
Nanodiagnostics Technologies and Applications 320<br />
In vivo Nanodiagnostics 322
CONTENTS xv<br />
Key Terms 324<br />
Review Questions 324<br />
9 Government Influence on Nanotechnology 327–388<br />
Government Promotion of Advancements<br />
in Nanomedicine 328<br />
U.S. Government Funding and Initiatives 328<br />
U.S. Federal Funding for Nanomedicine 328<br />
U.S. Presidential Influence 328<br />
The Federal Government’s National Nanotechnology<br />
Initiative (NNI) 329<br />
The U.S. National Institutes of Health (NIH) 330<br />
The U.S. National Institute of Standards and Technology<br />
(NIST) 334<br />
The U.S. National Science Foundation (NSF) 336<br />
The U.S. National Cancer Institute (NCI) Alliance for<br />
Nanotechnology in Cancer 337<br />
U.S. Department of Defense (DOD) Defense Advanced<br />
Research Projects Agency (DARPA) 338<br />
U.S. State Funding and Initiatives 339<br />
Missouri 339<br />
New York 340<br />
Texas 341<br />
Australian Government Funding and Initiatives 343<br />
Victorian Government 344<br />
Canadian Government Funding and Initiatives 345<br />
European Funding and Initiatives 347<br />
Nano2Life 347<br />
European Technology Platform (ETP) in Nanomedicine 349<br />
Singaporean Government Funding and Initiatives 351<br />
Mexican Government Funding and Initiatives 352<br />
Global Institutional Collaborations 352<br />
Global Enterprise for Micro-Mechanics and<br />
Molecular Medicine (GEM 4 ) 353
xvi<br />
CONTENTS<br />
Government Evaluation, Policy and Regulation of Nanotechnology 355<br />
The United States Federal Oversight 356<br />
The U.S. Food and Drug Administration<br />
Nanotechnology Task Force 356<br />
The U.S. Environmental Protection Agency 359<br />
The U.S. National Science and Technology Council (NSTC) 360<br />
The U.S. National Research Council 361<br />
The U.S. Patent and Trademark Office 362<br />
The Project on Emerging Nanotechnologies 363<br />
State and Local Oversight 363<br />
California State Regulation of Carbon Nanotubes 363<br />
Berkeley, California and the Regulation of Nanoparticles 364<br />
The European Union 365<br />
The United Kingdom 366<br />
The Royal Society’s Analysis on the Safety of Nanoparticles 367<br />
The Council for Science and Technology (CST) 368<br />
Nanotechnology Engagement Group (NEG) 368<br />
The Department for Environment, Food and Rural Affairs 369<br />
British House of Lords 370<br />
The Government of the United Kingdom 371<br />
Australia 372<br />
Australian Government Department of Health<br />
and Ageing 372<br />
Monash University and Its Influence on Australia’s<br />
Regulatory Framework 373<br />
Canada 373<br />
Environment Canada 374<br />
Health Canada 374<br />
International Efforts at Nanotechnology Regulation 375<br />
The International Risk Governance Council (IRGC) 375<br />
The International Council on Nanotechnology (ICON) 376<br />
The Organization for Economic Cooperation and<br />
Development (OECD) 377
CONTENTS xvii<br />
The International Center for Technology Assessment (ICTA) 378<br />
The International Union of Food, Farm and<br />
Hotel Workers (IUF) 379<br />
US/EU Collaborative Efforts 380<br />
Chapter Summary 381<br />
Government Promotion of Advancements in Nanomedicine 381<br />
Government Evaluation, Policy and Regulation<br />
of Nanotechnology 383<br />
Key Terms 386<br />
Review Questions 387<br />
10 Future Concepts in Nanomedicine 389–426<br />
Nanorobotics and Medicine 389<br />
Nanomolecular Motors and Gears 390<br />
Rotaxane-Based Nanomotors 391<br />
Nucleic Acid-Based Nanomotors 393<br />
Nanotube-Based Nanomotors 394<br />
Nanogears 396<br />
Nanocomputers 396<br />
Electronic Nanocomputers 397<br />
Mechanical Nanocomputers 398<br />
Chemical and Biological Nanocomputers 401<br />
Quantum Nanocomputers 402<br />
Therapeutic Nanorobots 404<br />
Respirocytes 405<br />
Clottocytes 406<br />
Microbivores 407<br />
Chromallocytes 409<br />
Personalized Nanomedicine 410<br />
Nanoparticle-Based Theranostics 410<br />
Whole-Genome Diagnostics 411<br />
Nanonephrology 414
xviii<br />
CONTENTS<br />
Nanoneural Interfaces 415<br />
Optical Imaging at the Nanoscale 417<br />
Artificial Intelligence and “the Singularity” 420<br />
Chapter Summary 422<br />
Nanorobotics and Medicine 422<br />
Personalized Nanomedicine 424<br />
Key Terms 425<br />
Review Questions 425<br />
Appendixes 427–477<br />
Glossary 427<br />
Suggested Readings 460<br />
Books and Compilations 460<br />
Figure and Table Acknowledgments 479<br />
Index 481<br />
About the Author 493
Acknowledgment<br />
I would like to sincerely thank all the scientists and doctors who allowed<br />
for the reprinted publication of their research and data in this book. It is<br />
your undying and unselfish pursuit of advances in nanomedicine that will<br />
transform diagnostics and therapeutics as we know it and inspire the next<br />
generation of nanomedical researchers. My hat is off to each and every one<br />
of you.
Preface to the Professor<br />
As I researched the currently available textbooks covering the basic<br />
principles, applications and promise of nanotechnology as it applies to<br />
medicine, I noted a dearth of introductory material tailored specifically<br />
for students. While a number of comprehensive books exist outlining the<br />
promise of the nanosciences as they apply to medical applications, including<br />
most recent advances in medical research, these texts fail to properly<br />
introduce the student to nanoscience and nanotechnology as it applies first<br />
to biology and to potential therapeutics and diagnostics applications. Thus<br />
this text is devoted to the basic principles of nanotechnology, focusing<br />
on nanomaterials and nanoparticles, as with respect to the whole of<br />
nanoscience, these sectors hold the most promise for the future of medicine.<br />
It is tailored towards real-world applications of medical nanotechnologies<br />
with a heavy emphasis on specific examples from the existing literature<br />
available in this area. It is NOT (with the exception of Chapter 10) a<br />
compilation of thoughts and essays describing what may occur in the<br />
realm of nanomedicine in the distant future. The book is written at an<br />
introductory level to allow the student to have a firm grasp of the principles<br />
of nanotechnology first, followed by a discussion on the relationship<br />
between nanoscience and biology, and ending with the majority of the text<br />
outlining medical applications. As much of the content is not considered
xxii<br />
PREFACE TO THE PROFESSOR<br />
to be central scientific dogma but rather exciting yet preliminary research,<br />
the text is often written in review format, giving full credit to researchers<br />
for their published findings and citing appropriate scientific articles. As the<br />
scientific discipline of medical nanoscience advances, it is anticipated that<br />
this text will mature into a more basic and fundamental description of the<br />
field as is the case for biology or chemistry.<br />
I have organized the contents of this book to emphasize the basic<br />
principles of nanotechnology and how they might apply to the betterment<br />
of mankind through an improvement in human health. I point out that<br />
nanoscience, like all disciplines, is not an exact science, and that much of the<br />
material presented is based on hypothesis and backed up by experimental<br />
results. A great deal of emphasis is placed on the published experimental<br />
research and results of key leaders in the field. To accomplish this task, I<br />
have included:<br />
1. A comprehensive description of the basic principles and<br />
definitions of nanoscience and nanotechnology.<br />
2. A breakdown in the origins and chemical makeup of some of the<br />
most widely used nanomaterials and nanoparticles in medical<br />
research.<br />
3. A concentrated focus on detailing the relationship between<br />
nanoscience and biology.<br />
4. Descriptions of and principles behind the most high-profile<br />
nanotechnologies, nanomaterials and nanoparticles currently<br />
studied for applications in medicine.<br />
5. An extensive review of the top five areas of therapeutic focus<br />
involving nanotechnology.<br />
6. An entire section on in vivo targeting of nanoparticles utilizing<br />
cell type-specific ligands.<br />
7. A breakdown of the principles behind the use of nanoparticles<br />
in thermal ablation therapy, emphasizing the most high-profile<br />
published examples.<br />
8. An overview of the use of nanoparticles to deliver drugs in vivo<br />
9. Descriptive explanations behind the principles and detail on<br />
the use of nanomaterials and nanoparticles as contrast agents in<br />
medical diagnostic applications.
PREFACE TO THE PROFESSOR xxiii<br />
10. A glimpse into the future of nanomedicine and what the student<br />
can expect to evolve regarding nanotechnology-based diagnostics<br />
and therapeutics, finishing with the intriguing concept of the<br />
“Singularity.”<br />
This book is organized to naturally transition from a basic understanding<br />
of the principles, including physics, behind, for example, nanoparticles<br />
and nanomaterials, to how these principles might be exploited and used to<br />
treat or at the very least efficiently diagnose human disease or anomalies.<br />
Each chapter introduces topics and vocabulary at a very basic level and<br />
transitions to more advanced coverage as the student’s knowledge level<br />
matures.<br />
Chapter 1 begins with an overview of the origins of nanoscience<br />
and nanotechnology and progresses to explain the physical principles<br />
behind nanostructures and nanotools. Although not related to medicine,<br />
industrial applications of both nanostructures and nanotools are cited as<br />
examples to give the student a firm understanding not only of the benefits<br />
of nanoscience but also about how the physics of nanotechnology can<br />
be exploited for gain. The chapter finishes with a shift in focus towards<br />
the relationship between nanoscience and biology, thus introducing the<br />
student to the major focus of this book.<br />
In Chapter 2, I hope in on the basic potential for nanotechnology,<br />
centered around nanoparticles and nanomaterials, to impact therapeutics,<br />
specifically that in relation to cancer. A breakdown in the types of<br />
nanoparticles currently being explored for cancer treatment primarily<br />
via hyperthermia is presented, with specifics on different modes of<br />
action. In this section I describe the physics, principles and therapeutic<br />
concepts behind the use of nanoparticles, combined with external fields<br />
for thermal ablation. This is followed by a comprehensive breakdown of<br />
targeting nanoparticles to specific sites for tumor cell ablation outlining<br />
targeting agents and targeting moiety attachment. The chapter finishes<br />
with an overview of the use of nanoparticles for anticancer drug delivery,<br />
describing both locally and intravenously applied therapeutic platforms.<br />
Chapter 3 focuses on nanotechnology-driven tissue engineering<br />
applications such as scaffolds for tissue repair. It begins with a breakdown<br />
of the most high-profile types of nanofibers used in scaffold development<br />
and details their compositions. This includes both natural and synthetic<br />
examples. Techniques for the synthesis of certain nanofiber types are
xxiv<br />
PREFACE TO THE PROFESSOR<br />
described, such as electrospinning, and the chapter concludes with realworld<br />
examples of nanofiber applications in tissue engineering, such as for<br />
bone and vasculature repair.<br />
Chapter 4 covers the impact that nanotechnology is beginning to<br />
have on neuroscience and the treatment of neurodegenerative disease.<br />
Examples of neuronal/neural matrices based on nanomaterials are cited<br />
and described. This is followed by a special section on how nanomaterials<br />
might effectively address the age-old problem of therapeutic delivery<br />
across the blood-brain barrier (BBB). Specific examples of nanomaterial/<br />
nanoparticle strategies for BBB crossing are described and backed up by<br />
in vivo data from a number of researchers. Chapter 4 also cites examples<br />
of the neuroprotective effects of some nanoparticle systems such as<br />
those designed to be anti-oxidants and finishes with by describing some<br />
intriguing examples of combination nanoparticle/cell carrier strategies for<br />
applications in clinical neuroscience.<br />
Surgery is perhaps the oldest form of medicine known to man and<br />
thus I have dedicated an entire chapter to nanotechnology’s emerging<br />
impact on this field. Chapter 5 begins with a description of the need for<br />
new biocompatible biomedical implant coatings. This is followed by a<br />
description of several nanotechnology-based implant coatings currently<br />
under development, including, for example, those of nanostructured<br />
hydroxyapatite and metalloceramic origins. Surgery is addressed next<br />
with an explanation of the need to better minimize surgical damage and<br />
illustrations of nanotechnologies to address this issue such as nanopulses<br />
and next-generation nanocoatings for surgical instruments. Next the<br />
chapter addresses the need for better wound-healing technologies and<br />
outlines examples of how nanotechnology is already making significant<br />
inroads into this area with applications such as nanosutures, nanofiberbased<br />
bandages and antibiotic nanocoatings. Chapter 5 ends with a look<br />
at laser- and non-laser-based intracellular nanosurgery and how it is<br />
impacting basic biomedical research and may impact therapeutics in the<br />
future.<br />
Chapter 6 tackles both the current potential and limitations of<br />
existing cell culture methods and how nanotechnology may provide new<br />
avenues for growing cells for research purposes as well as cell transplant<br />
therapeutics. A brief history of cell culture is given and the most popular<br />
cells for manipulation in vitro are described. The chapter’s emphasis is on<br />
the development of new cell culture matrices that more effectively mimic
PREFACE TO THE PROFESSOR xxv<br />
the natural in vivo environment. A comparison of 2D vs. 3D cell culture<br />
methods is made illustrating the advantages of 3D for both scale and in<br />
vivo mimicry. Examples of nanomaterial-based scaffolds for cell culture<br />
are cited, including those of both natural and synthetic origin. Techniques<br />
for the efficient cellularization of nanoscaffolds are also described and the<br />
chapter concludes with some unique applications of titanium and magnetic<br />
nanoparticle systems for cell culture.<br />
Chapter 7 is therapeutically centric and focuses on the use of<br />
nanoparticles as drug delivery vehicles. The basic principles behind both<br />
active and passive drug delivery are outlined and this is followed by a<br />
thorough description of synthetic and natural nanomaterials currently<br />
under study as drug delivery platforms. Examples include the widely<br />
studied PLGA and PEG synthetic polymers along with some controversial<br />
delivery systems such as fullerenes. It concludes with a section listing and<br />
describing naturally occurring nanomaterials used or under study for drug<br />
delivery such as liposomes and gelatin.<br />
Aside from therapeutic applications, diagnostics is clearly the area of<br />
medicine where nanotechnology holds the most promise. Chapter 8 is<br />
dedicated to nanotechnology-driven advancements in diagnostics that may<br />
allow for earlier and/or more efficient and sensitive detection of disease.<br />
The chapter begins with descriptions and illustrations of examples in in<br />
vitro-based nanodiagnostics such as nanobiochips and nanobiosensors.<br />
Nanolaser spectroscopy and nanoproteomics are also covered in this<br />
section. A detailed breakdown of the most widely studied nanotechnologies<br />
and methods for in vivo nanodiagnostics follows the in vitro section. Gold<br />
and magnetic nanoparticles acted upon by external fields for imagery are<br />
cited as examples, and intriguing research into the use of liposomes and<br />
micelles to deliver metal nanoparticles for in vivo diagnostics concludes<br />
the chapter.<br />
In Chapter 9, I have chosen to focus on governmental influence on<br />
nanotechnology and, where possible, emphasize the effects it is beginning<br />
to have on the emerging field of nanomedicine. The chapter is broken<br />
down into two primary sections. The first illustrates government funding<br />
and promotion of advancements in nanotechnology. The second seeks<br />
to give the student a thorough understanding of government’s attempts<br />
at regulating this rapidly maturing area of science. I have delineated the<br />
growing influence of major world governments on nanotechnology and<br />
have completed both sections with examples of globally and internationally
xxvi<br />
PREFACE TO THE PROFESSOR<br />
coordinated efforts at impacting nanotechnology in general and<br />
nanomedicine in particular.<br />
The book concludes with a glimpse into the conceptual future of<br />
nanomedicine in Chapter 10. Here I take many of the more futuristic<br />
concepts and examples regarding medical applications and advancements<br />
of nanotechnology from leading nanoscientists and theoreticists around<br />
the world and describe them in enough detail to capture and peak the<br />
student’s interest and imagination in what may lie ahead for the future of<br />
diagnosis, therapy and nanotechnology itself.<br />
It should be noted that at the end of each chapter I have drafted a set of<br />
key terms in the form of a glossary. In choosing the terms I have attempted<br />
to drive home the most important points made within that chapter’s text.<br />
In addition, I have also listed a review section of questions at the end of<br />
each chapter that are designed to provoke the student’s intellect and grasp<br />
of the contents of that particular chapter. The questions are meant to be<br />
thought-provoking and many may be answered correctly in a number of<br />
different ways given the essay format. The answers to these questions can<br />
be found at www.understandingnano.org. It is up to the discretion of the<br />
professor whether or not to utilize these additions to each chapter, but I am<br />
convinced that if the glossary and review sections are properly studied the<br />
student will have a firm understanding of the most critical concepts from<br />
each chapter and section of this book.<br />
As always, I am most certainly appreciative of comments and criticisms<br />
regarding the content and format of Understanding Nanomedicine: An<br />
Introductory Textbook. If you have input or suggestions pertaining to this<br />
book, I’d love to hear from you as your response will most certainly impact<br />
future editions.<br />
Rob Burgess<br />
www.understandingnano.org
Preface to the Student<br />
As of the writing of this publication there is no introductory textbook<br />
available which sufficiently teaches the emerging concepts and principles<br />
behind nanotechnology and its potential enormous impact on the field of<br />
medicine. The science of nanotechnology is maturing at such a rapid pace<br />
that I feel the time is now to address its most promising area of application,<br />
and that is medicine. It is crucial for the future scientists, researchers and<br />
medical specialists of our time to have a strong grasp and understanding<br />
of both the potential for nanotechnology to revolutionize therapeutics and<br />
diagnostics, and the risks associated with these endeavors. I firmly believe<br />
that if you take the time to study and enjoy this introductory text you will<br />
not only appreciate the future impact that nanotechnology will have on<br />
man’s health and well-being but also begin to form your own concepts and<br />
ideas on how to realize that impact.<br />
With the exception of Chapter 10, I have based this composition of<br />
the concepts and examples presented in this book solely on hard facts and<br />
published data. I have not, for example, glossed over the possibility of<br />
nanoparticle toxicity but rather cited references to it where appropriate.<br />
The book is heavily focused on the use of nanoparticles as thermal ablation<br />
agents or drug delivery vehicles, as these areas are perhaps the largest areas<br />
of focus for nanotechnology with respect to medicine today. In addition,
xxviii<br />
PREFACE TO THE STUDENT<br />
as much of the content is not considered to be central scientific dogma but<br />
rather exciting yet preliminary research, the text is often written in review<br />
format, describing profound data and research and giving full credit to<br />
scientists and medical doctors for their published findings by citing<br />
appropriate scientific articles.<br />
The chapters are organized largely as self-contained in subject material,<br />
beginning with non-medical definitions and descriptions of nanotechnology<br />
and transitioning to biology and putative uses of nanotechnology<br />
in medicine. The material transitions from the fundamentals of nanoscience<br />
to applications of those fundamentals and physical properties for the<br />
betterment of medicine and medical research. Each chapter is followed by<br />
a glossary of key terms and a set of review questions. I strongly urge you to<br />
study these in order to gain a thorough understanding of that particular<br />
chapter’s material.<br />
It is also recommended that the assigned material be read and<br />
thoroughly reviewed prior to the corresponding lecture. In addition,<br />
I suggest that you review the key terms at the end of each chapter and<br />
make an attempt at answering the review questions prior to the material<br />
being covered either in class or during study sessions. The answers to<br />
these questions can be found at www.understandingnano.org. This will<br />
allow you to have a basic grasp of the principles and subjects presented<br />
or discussed and make the lecture series more interesting and enjoyable.<br />
Also, take thorough notes in class and recopy those notes, preferably on<br />
the same day to re-emphasize the material. You will retain it longer and<br />
have less difficulty for recall during exams. If you are so inclined it is also<br />
recommended that you reread the text covered by lecture after class to aid<br />
understanding and retention.<br />
Finally, I am always seeking comments, including both praise and<br />
criticism, regarding my manuscripts and publications. I cannot obtain<br />
more legitimate and valuable feedback than from the students for which<br />
this book was written. If you have ideas or suggestions for how I might<br />
make future editions of this book more useful, please contact me.<br />
Rob Burgess<br />
www.understandingnano.org
Reviewers<br />
The author and publisher would like to express their sincere appreciation<br />
to a number of scientists and researchers who have taken considerable time<br />
and effort to assist with the development of this book. Nanotechnology is<br />
a diverse and wide-ranging scientific discipline, and we owe a great deal to<br />
the specialists who reviewed this material:<br />
Rockford K. Draper<br />
Professor, Molecular & Cell Biology and Chemistry<br />
University of Texas at Dallas<br />
Richardson, Texas<br />
Gareth Hughes<br />
President and CEO<br />
Medical Nanotechnologies, Inc.<br />
Dallas, Texas