Table Of ContentBioNanotechnology
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
