BioNanotechnology Copyright © 2007 by Morgan & Claypool All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means—electronic, mechanical, photocopy, recording, or any other except for brief quotations in printed reviews, without the prior permission of the publisher. BioNanotechnology Elisabeth S. Papazoglou, Aravind Parthasarathy www.morganclaypool.com ISBN: 1598291386 paperback ISBN: 9781598291384 paperback ISBN: 1598291394 ebook ISBN: 9781598291391 ebook DOI: 10.2200/S00051ED1V01Y200610BME007 A Publication in the Morgan & Claypool Publishers’ series SYNTHESIS LECTURES ON BIOMEDICAL ENGINEERING #7 Lecture #7 Series Editor: John D. Enderle, University of Connecticut Library of Congress Cataloging-in-Publication Data Series ISSN: 1930-0328 print Series ISSN: 1930-0336 electronic First Edition 10 9 8 7 6 5 4 3 2 1 BioNanotechnology Elisabeth S. Papazoglou, Aravind Parthasarathy School of Biomedical Engineering Drexel University SYNTHESIS LECTURES ON BIOMEDICAL ENGINEERING #7 M &C M o r g a n & C l a y p o o l P u b l i s h e r s iv ABSTRACT This book aims to provide vital information about the growing field of bionanotechnology for undergraduate and graduate students, as well as working professionals in various fields. The fundamentals of nanotechnology are covered along with several specific bionanotechnology applications, including nanobioimaging and drug delivery which is a growing $100 billions industry. The uniqueness of the field has been brought out with unparalleled lucidity; a balance between important insight into the synthetic methods of preparing stable nano-structures and medical applications driven focus educates and informs the reader on the impact of this emerging field. Critical examination of potential threats followed by a current global outlook completes the discussion. In short, the book takes you through a journey from fundamentals to frontiers of bionanotechnology so that you can understand and make informed decisions on the impact of bionano on your career and business. KEYWORDS Bionanotechnology, Bionano initiatives, Bionano threats, Gold nanoparticles, Nano- bioimaging, Nano drug-delivery (or nano-vectors or targeted drug-delivery), Nano synthetics, and Bionanotoxicology, MRI, Titania nanoparticles, and Zinc nanoparticles. v Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 0.1 Bionanotechnology: A Historical Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 0.2 Nanotechnology and Bionanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 0.3 Notable Nanoimages in Bionanotechnology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5 0.3.1 AFM-Qd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 0.3.2 Nano-drug Delivery Chip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 0.3.3 Atomic Force Microscopy Image (AFM) of SWNT. . . . . . . . . . . . . . . . . .7 0.3.4 Scanning Electron Microscopy Image (SEM) of SWNT. . . . . . . . . . . . . .7 0.4 Opportunities and Challenges of Bionanotechnology . . . . . . . . . . . . . . . . . . . . . . . . 8 0.5 Growth potential of Nanotechnology and Related Expenditures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12 1. The Significance of Nano Domain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 1.1 Limitations of Micron Size. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 1.2 Need for Nano-Size—Surface Volume Ratio Significance . . . . . . . . . . . . . . . . . . . 15 1.3 Significance and Key Features of Nano-Size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 1.4 Derivation of Bohr’s Atomic Radius of a Hydrogen Atom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 1.5 Comparison of Particle Behavior at Nano-Size to Macro Size: Gold and Titania. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23 1.6 Advantages of Scaling Down—Nano-Size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27 2. Nano Drug Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31 2.1 Conventional Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 2.1.1 First Pass Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 2.1.2 Routes of Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.2 Targeted Drug Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .34 2.3 Chemistry of Drug Delivery Vehicles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35 2.3.1 Nanocapsules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35 2.3.2 Unilamellar Liposomal Vesicles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 vi BIONANOTECHNOLOGY 2.3.3 Nanoparticles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36 2.3.4 Microemulsions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 2.4 Delivery Profiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 2.4.1 Rate-Preprogrammed Drug Delivery Systems . . . . . . . . . . . . . . . . . . . . . . 39 2.4.2 Activation-Modulated Drug Delivery Systems . . . . . . . . . . . . . . . . . . . . . . 39 2.4.3 Feedback-Regulated Drug Delivery Systems. . . . . . . . . . . . . . . . . . . . . . . .40 2.4.4 Site-Targeting Drug Delivery Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 2.5 The Role of Nanotechnology in Drug Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . .40 2.5.1 Transdermal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 2.5.2 Blood Brain Barrier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 2.6 Advantages of Targeted Drug Delivery Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43 3. BioNanoimaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 3.1 Quantum Dots. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47 3.2 Ultrasound Contrast Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .52 3.3 Magnetic Nanoparticles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .60 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63 4. Successful Applications of Bionanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 4.1 Nanostructures and Nanosystems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 4.1.1 Nanopore Technology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69 4.1.2 Nano Self-Assembling Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 4.1.3 Cantilevers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 4.1.4 Nanoarrays. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 4.2 Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 4.2.1 Quantum Dots (QDs). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71 4.2.2 Paramagnetic Iron Oxide Crystals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 4.2.3 Dendrimers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 4.2.4 Carbon Nanotubes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74 4.2.5 Nanosomes and Polymersomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 4.3 In Vitro Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 4.4 Medical Application of Nanosystems and Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 4.4.1 Drug Delivery Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 4.4.2 Nanoparticles in Molecular Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 4.5 Summary and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79 CONTENTS vii 5. Synthesis of Gold, Titania, and Zinc Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 5.1 Synthesis of Gold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 5.1.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 5.1.2 Brust Method of Synthesis of Thiol Derivatized Gold NPs by Biphasic Reduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .85 5.1.3 Gold Colloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 5.1.4 Gold Nanofilm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 5.1.5 Gold Nanorods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 5.2 Synthesis of Titania Nanostructures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 5.2.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 5.2.2 Solvo-Thermal Synthesis of Titania Nano Crystals. . . . . . . . . . . . . . . . . . 89 5.2.3 Sol-Gel Template Synthesis of Titania Nano Tubes and Rods . . . . . . . 89 5.2.4 Overview of Other Synthesis Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 5.3 Synthesis of Zinc Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 5.3.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 5.3.2 The Solid-Vapor Synthesis of ZnO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .93 5.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 5.1.1 Brust Method of Synthesis of Thiol Derivatized Gold NPs by Biphasic Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 5.2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 5.2.1 Solvo-Thermal Synthesis of Titania Nano Crystals. . . . . . . . . . . . . . . . .102 5.2.2 Sol-Gel Template Synthesis of Titania Nano Tubes and Rods . . . . . . 102 5.2.3 Overview of Other Synthesis Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . .103 5.3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 5.3.1 The Solid-Vapor Synthesis of ZnO: Horizontal Tube Furnace . . . . . . 104 5.3.2 Wurtzite Structure of ZnO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 6. Is Bionanotechnology a Panacea?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109 6.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 6.2 Primary Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 6.3 Assessing Potential Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 6.3.1 Inhalation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .112 6.3.2 Contact/Dermal Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .112 6.3.3 Other Routes of Contact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 6.3.4 Environmental Impacts of NPs and the Food Chain . . . . . . . . . . . . . . . 113 6.3.5 Explosion Hazards. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .114 viii BIONANOTECHNOLOGY 6.4 Lessons from the Past . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 6.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 7. Roadmap to Realization of Bionanotechnology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .121 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 7.2 Nano Vision: the Futuristic Goals of Bionanotech . . . . . . . . . . . . . . . . . . . . . . . . . 121 7.3 Working toward Realization: Current Progress. . . . . . . . . . . . . . . . . . . . . . . . . . . .122 7.4 Screenshot of Reality: Bionano-Unbiased/Uncensored . . . . . . . . . . . . . . . . . . . . . 123 7.5 The Nano Mission: Roadmap to Realization of Translation Research. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .124 7.5.1 Bionano in the US . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 7.5.2 Bio-Nano in Japan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .126 7.5.3 Bio-Nano in UK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 7.5.4 UK–Japan Joint Initiative for Bionanotechnology . . . . . . . . . . . . . . . . . . 126 7.5.5 The EU Initiative in Bionanotech . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 7.5.6 Bionano in Asia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Author Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 1 Introduction 0.1 BIONANOTECHNOLOGY: A Historical Perspective The first written concept of the possibility to manipulate matter at the nano-level was proposed by Richard Feynman who during his lecture “Room at the Bottom” discussed the use of atomic blocks to assemble at a molecular level [1, 2]. In this now famous quote, Feynman argues that, “The principles of physics, as far as I can see, do not speak against the possibility of maneuvering things atom by atom. It is not an attempt to violate any laws; it is something, in principle, that can be done; but in practice, it has not been done because we are too big” [2, 3]. In today’s definitions, “nanotechnology is the understanding and control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications” [2–4]. The nanotechnology field was however really established by the work of Eric Drexler, Richard Smalley and in the bionanotechnology arena by Chad Mirkin. a) Richard Smalley Dr. Richard E. Smalley, a chemistry professor at Rice University, pioneered the field of nan- otechnology and shared a Nobel Prize in 1996 for the development of bucky-balls, shown in Fig. 0.1. His contribution to nanotechnology is significant and the research team he established between Rice and the M.D. Anderson Cancer center has been a strong innovation force in the area of bionanotechnology. Dr. Richard E. Smalley—Nobel Laureate (June 6, 1943–October 28, 2005) 2 BIONANOTECHNOLOGY FIGURE 0.1: Fullerene (Bucky ball)—discovery by Dr. Richard Smalley Smalley along with Robert Curl at Rice and Sir Harold Kroto at the University of Sussex discovered fullerenes, or bucky-balls, these unexpected spherical arrangements composed of 60 carbon atoms. Outside this fundamental, seminal contribution, Smalley’s team continued with innovative contributions that impacted nanotechnology and its biomedical applications. These include a practical way to produce large quantities of carbon nano tubes, a vital step in the commercial development of nanotechnology, and the founding of Carbon Nanotech- nologies in 2000, to produce large quantities of nanotubes for research and commercialization. b) Eric Drexler K. Eric Drexler received his doctorate degree in Molecular Nanotechnology from MIT in 1991, the first degree of its kind. As a researcher, author, and policy advocate he has been one of the pioneers to focus on emerging technologies and their impact for the future. He founded the Foresight Institute and presently serves as the Chief Technical Advisor of Nanorex, a company that develops software for the design and simulation of molecular ma- chine systems. His thought provoking publications “Engines of Creation: The Coming Era of Nanotechnology,” “Nanosystems: Molecular Machinery, Manufacturing, and Computation,” and “Unbounding the Future: The Nanotechnology Revolution,” made great impact by in- troducing the very topic of nanotechnology to many, and exposing an engineering approach