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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

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