7194 c000

q 2006 by Taylor & Francis Group, LLC
Dedication
To the loving memory of my dad,
Mustafa Amiji, and to my mom, Shirin Amiji
Foreword
We are at the threshold of a new era in cancer treatment and diagnosis, brought about by the
convergence of two disciplinesmaterials engineering and life sciencesthat 30 years ago might
have been difficult to envision. The product of this curious marriage, nanobiotechnology, is yielding
many surprises and fostering many hopes in the drug-development space. Nanoparticles,
engineered to exquisite precision using polymers, metals, lipids, and carbon, have been combined
with molecular targeting, molecular imaging, and therapeutic techniques to create a powerful set of
tools in the fight against cancer. The unique properties of nanomaterials enable selective drug
delivery to tumors, novel treatment methods, intraoperative imaging guides to surgery, highly
sensitive imaging agents for early tumor detection, and real-time monitoring of response to
treatment.
Using nanotechnology, it may be possible to leap over many of the hurdles of cancer drug
delivery that have confounded conventional drugs. These hurdles include hindered access to the
central nervous system through the bloodbrain barrier, sequestration by the reticulo-endothelial
system, inability to penetrate the interior of solid tumors, and overcoming multi-drug resistance
mechanisms. These obstacles can be mitigated by manipulating the size, surface charge,
hydrophilicity, and attached targeting ligands of a therapeutic nanoparticle.
The novelty of using nanotechnology for medical applications presents its own challenges,
similar in many ways to the challenges faced by the introduction of the first synthetic protein-based
drugs. In the early 1980s, protein-based drugs offered an entirely new approach to targeting and
treating disease. They could be engineered to be highly specific and even offered the capability of
separating the targeting and therapeutic functions of a drug, such as when monoclonal antibodies
are conjugated to cytotoxic agents. But monoclonal antibodies and recombinant protein-based
drugs necessitated a different approach to lead optimization, metabolism, and toxicity screening
from that of small-molecule drugs. Factors such as stability, immunogenicity, and species
specificity had to be considered and tested in ways that were not familiar to the developers of
traditional drugs.
Nanotechnology-based drugs will catalyze a reevaluation of optimization, metabolism, and
toxicity-screening protocols. Interactions between novel materials and biological pathways are
largely unknown but are widely suspected to depend heavily on physical and chemical
characteristics such as particle size, particle size distribution, surface area, surface chemistry
(including charge and hydrophobicity), shape, and aggregation statefeatures not usually
scrutinized for traditional drugs. Standard criteria for physicochemical characterization will have to
be established before safety testing can yield interpretable and reproducible results.
Would nanotechnology-based drugs be successful? All drugs have to run an obstacle course
through physiological and biochemical barriers. For monoclonal antibody drugs, only a minute
portion of an intravenously administered drug reaches its target. However, drugs based on
nanomaterials, including nanoparticles, have unique properties that enable them to specifically bind
to and penetrate solid tumors. Size and surface chemistries can be manipulated to facilitate
extravasation through tumor vasculature, or the therapeutic agent can be encapsulated in polymer
micelles or liposomes to prevent degradation and increase circulation half-life to improve the odds
of it reaching the target.
This level of functional engineering has not been available to either small-molecule or proteinbased drugs. For these drugs, modification of one characteristic, such as solubility or charge, can
have dramatic effects on other essential characteristics, such as potency or target specificity.
Nanoparticles, however, introduce a much higher degree of modularity and offer at least four
advantages over the antibody conjugates: (1) the delivery of a larger therapeutic payload per target
recognition event, enhancing potency; (2) the ability to carry multiple targeting agents, enhancing
selectivity; (3) the ability to carry multiple therapeutic agents, enabling targeted combination
therapies; and (4) the ability to bypass physiological and biological barriers.
We would all like to hasten the day when chemotherapythe administration of non-specific,
toxic anti-cancer agentsis relegated to medical history. Improvements in diagnostic screening
and the development of drugs that target specific biological pathways have begun to turn the tide
and contribute to a slow, yet consistent decline in death rates. While confirming that early diagnosis
and targeted therapies are pointing us in the right direction, the progress is still incremental.
Nanotechnology may be our best hope for overcoming many of the barriers faced by todays drugs
in the battle against cancer. The combined creative forces of engineering, chemistry, physics, and
biology will beget new and hopefully transformative options to old, intractable problems.
Piotr Grodzinski, Ph.D.
National Cancer Institute
Preface
With parallel breakthroughs occurring in molecular biology and nanoscience/technology, the newly
recognized research thrust on nanomedicine is expected to have a revolutionary impact on the
future of healthcare. To advance nanotechnology research for cancer prevention, diagnosis, and
treatment, the United States National Cancer Institute (NCI) established the Alliance for
Nanotechnology in Cancer in September 2004 and has pledged $144.3 million in the next five years
(for details, visit http://nano.cancer.gov). Among the approaches for exploiting developments in
nanotechnology for cancer molecular medicine, nanoparticles offer some unique advantages as
sensing, delivery, and image enhancement agents. Several varieties of nanoparticles are available,
including polymeric conjugates and nanoparticles, micelles, dendrimers, liposomes, and
nanoassemblies.
This book focuses specifically on nanoscientific and nanotechnological strategies that are
effective and promising for imaging and treatment of cancer. Among the various approaches
considered, nanotechnology offers the best promise for targeted delivery of drugs and genes to the
tumor site and alleviation of the side effects of chemotherapeutic agents. Multifunctional
nanosystems offer tremendous opportunity for combining more than one drug or using drug and
imaging agents. The expertise of world-renowned academic and industrial researchers is brought
together here to provide a comprehensive treatise on this subject.
The book is composed of thirty-eight chapters divided into seven sections that address the
specific nanoplatforms used for imaging and delivery of therapeutic molecules. Section 1 focuses
on the rationale and fundamental understanding of targeting strategies, including pharmacokinetic
considerations for delivery to tumors in vivo, multifunctional nanotherapeutics, boron neutron
capture therapy, and the discussion on nanotechnology characterization for cancer therapy, as well
as guidance from the U.S. Food and Drug Administration on approval of nanotechnology products.
Section 2 focuses on polymeric conjugates used for tumor-targeted imaging and delivery, including
special consideration on the use of imaging to evaluate therapeutic efficacy. In Section 3, polymeric
nanoparticle systems are discussed with emphasis on biodegradable, long-circulating nanoparticles
for passive and active targeting. Section 4 focuses on polymeric micellar assemblies, where
sophisticated chemistry is applied for the development of novel nanosystems that can provide
efficient delivery to tumors. Many of the micellar delivery systems are undergoing clinical trials in
Japan and other countries across the globe. Dendritic nanostructures used for cancer imaging and
therapy are discussed in Section 5. Section 6 focuses on the oldest nanotechnology for cancer
therapyliposome-based delivery systemswith emphasis on surface modification to enhance
target efficiency and temperature-responsive liposomes. Lastly, Section 7 focuses on other lipid
nanosystems used for targeted delivery of cancer therapy, including nanoemulsions that can cross
biological barriers, solid-lipid nanoparticles, lipoprotein nanoparticles, and DQAsomes for
mitochondria-specific delivery.
Words cannot adequately express my admiration and gratitude to all of the contributing authors.
Each chapter is written by a world-renowned authority on the subject, and I am deeply grateful for
their willingness to participate in this project. I am also extremely grateful to Dr. Piotr Grodzinski
for providing the Foreword. Drs. Fredika Robertson and Mauro Ferrari have done a superb job in
laying the foundation by providing a chapter entitled Introduction and Rationale for
Nanotechnology in Cancer. I am grateful to Professor Kinam Park at Purdue University,
Professor Robert Langer at MIT, and Professor Vladimir Torchilin at Northeastern University, who
have been my mentors and collaborators, as well as many other researchers from academia and
industry. Special thanks are due to the postdoctoral associates and graduate students in my
laboratory at Northeastern University who have been the soldiers in the trenches in our quest to
use nanotechnology for the targeted delivery of drugs and genes to solid tumors. Lastly, I am deeply
grateful to the wonderful people at Taylor & Francis-CRC Press, including Stephen Zollo, Patricia
Roberson, and many others, who have made the concept of this book into reality.
Any comments and constructive criticisms of the book can be sent to the editor at
m.amiji@neu.edu.
Editor
Dr. Mansoor M. Amiji received his undergraduate degree in pharmacy from Northeastern
University in 1988 and his PhD in pharmaceutics from Purdue University in 1992. His areas of
specialization include polymeric biomaterials, advanced drug delivery systems, and nanomedical
technologies.
Dr. Amijis research interests include the synthesis of novel polymeric materials for medical and
pharmaceutical applications; surface modification of cationic polymers by the complexationinterpenetration method to develop biocompatible materials; the preparation and characterization
of polymeric membranes and microcapsules with controlled permeability properties for medical
and pharmaceutical applications; target-specific drug and vaccine delivery systems for
gastrointestinal tract infections; localized delivery of cytotoxic and anti-angiogenic drugs for
solid tumors in novel biodegradable polymeric nanoparticles; intracellular delivery systems for
drugs and genes using target-specific, long-circulating, biodegradable polymeric nanoparticles; and
gold and iron-gold core-shell nanoparticles for biosensing, imaging, and delivery applications. His
research has received sustained funding from the National Institutes of Health (NIH), the National
Science Foundation (NSF), foundations, and local industries.
Dr. Amiji is Professor and Associate Chair of the Pharmaceutical Sciences Department and CoDirector of the Northeastern University Nanomedicine Education and Research Consortium
(NERC). The NERC oversees a doctoral training grant in nanomedicine science and technology
that was co-funded by the NIH and NSF. He has two published books, Applied Physical Pharmacy
and Polymeric Gene Delivery: Principles and Applications, along with numerous manuscript
publications. He has also received a number of awards, including the 2003 Eurand Award for
Innovative Oral Drug Delivery Research, Third Prize.
Dr. Amiji has supervised the research efforts of over 50 postdoctoral associates, doctoral and
masters level graduate students, and undergraduate honors students over the last 13 years. His
teaching responsibilities include the Doctor of Pharmacy (PharmD) program and graduate
programs (MS and PhD) in pharmaceutical sciences, biotechnology, and nanomedicine.
Contributors
Hamidreza Montazeri Aliabadi
Department of Pharmacy and Pharmaceutical
Sciences
University of Alberta
Edmonton, Alberta, Canada
Christine Allen
Department of Pharmaceutical Sciences
and
Department of Chemical Engineering and
Applied Chemistry
University of Toronto
Toronto, Ontario, Canada
Ashootosh V. Ambade
Department of Chemistry
University of Massachusetts at Amherst
Amherst, Massachusetts
Mansoor M. Amiji
Northeastern University
Boston, Massachusetts
Joseph M. Backer
SibTech, Inc.
Newington, Connecticut
Marina V. Backer
SibTech, Inc.
Newington, Connecticut
You Han Bae
Department of Pharmaceutics and
Pharmaceutical Chemistry
University of Utah
Salt Lake City, Utah
Lajos P. Balogh
Department of Radiation Medicine
and
Department of Cellular Stress and
Cancer Biology
Roswell Park Cancer Institute
Buffalo, New York
Rolf F. Barth
Department of Pathology
The Ohio State University
Columbus, Ohio
Reina Bendayan
Tania Betancourt
The University of Texas at Austin
Austin, Texas
D. Bhadra
Dr. H.S. Gour University
Sagar, India
S. Bhadra
Sagar, India
Sangeeta N. Bhatia
HarvardMIT Division of Health Sciences
and Technology
Massachusetts Institute of Technology
Cambridge, Massachusetts
Sarathi V. Boddapati
Lisa Brannon-Peppas
Austin, Texas
Mark Butler
Department of Chemical Engineering
and Applied Chemistry
John C. Byrd
Division of HematologyOncology
NCI Comprehensive Cancer Center
Columbus, Ohio
Robert B. Campbell
Shing-Ming Cheng
Gerard G. M. DSouza
Marina A. Dobrovolskaia
Nanotechnology Characterization Laboratory
NCI Frederick
Frederick, Maryland
Amber Doiron
Austin, Texas
P. K. Dubey
Dr. H. S. Gold University
Sagar, India
Omid C. Farokhzad
Department of Anesthesiology, Perioperative
and Pain Medicine
Brigham and Womens Hospital and Harvard
Medical School
Mauro Ferrari
The Brown Foundation Institute of
Molecular Medicine
M. D. Anderson Cancer Center
and
Alliance for Nanohealth
The University of Texas
Houston, Texas
Alberto A. Gabizon
Oncology Institute
Shaare Zedek Medical Center and
Hebrew University
Jerusalem, Israel
Jinming Gao
Simmons Comprehensive Cancer Center
University of Texas Southwestern
Medical Center
Dallas, Texas
Hamidreza Ghandehari
University of Maryland
Baltimore, Maryland
Todd J. Harris
and Technology
Mitsuru Hashida
Department of Drug Delivery Research
Graduate School of Pharmaceutical Sciences
Kyoto University
Sakyo-ku, Kyoto, Japan
Yuriko Higuchi
Kyoto University
Kang Moo Huh
Department of Polymer Science
and Engineering
Chungnam National University
Yuseong-Gu, Daejeon, South Korea
Edward F. Jackson
Division of Diagnostic Imaging
The University of Texas M. D. Anderson
Cancer Center
Houston, Texas
N. K. Jain
Sagar, India
Eun-Kee Jeong
Department of Radiology
University of Utah
Ji Hoon Jeong
Department of Pharmaceutics and
University of Utah
Sangyong Jon
Department of Life Science
Gwangju Institute of Science and Technology
Gwangju, South Korea
Shigeru Kawakami
Kyoto University
Mohamed K. Khan
Department of Radiation Medicine
and
Department of Cellular Stress and
Cancer Biology
Roswell Park Cancer Institute
Buffalo, New York
Chalermchai Khemtong
Medical Center
Dallas, Texas
Sun Hwa Kim
Department of Biological Sciences
Korea Advanced Institute of Science
and Technology
Daejeon, South Korea
Andras G. Lacko
Departments of Molecular Biology and
Immunology
University of North Texas Health Science
Center
Fort Worth, Texas
Robert Langer
Department of Chemical Engineering
Afsaneh Lavasanifar
Department of Pharmacy and Pharmaceutical
Sciences
Eun Seong Lee
Amorepacific Corporation/R&D Center
Giheung-gu Yongin-si Gyeonggi-do
South Korea
Helen Lee
Robert J. Lee
and
NSF Nanoscale Science and
Engineering Center
Columbus, Ohio
Tae-il Kim
School of Chemistry and Molecular
Engineering
Seoul National University
Seoul, South Korea
Sang Cheon Lee

Nanomaterials Application Division
Korea Institute of Ceramic Engineering and
Technology
Guemcheon-gu, Seoul, South Korea
Sushma Kommareddy
Chun Li
M. D. Anderson
Cancer Center
Houston, Texas
Vinod Labhasetwar
Departments of Pharmaceutical Sciences and
Biochemistry and Molecular Biology
University of Nebraska Medical Center
Omaha, Nebraska
Yongqiang Li
Bruce R. Line
Department of Radiology, and Greenebaum
Cancer Center
Baltimore, Maryland
Jubo Liu
Zheng-Rong Lu
Departments of Pharmaceutics and
University of Utah
S. Mahor
Dr. H. S. Gour University
Sagar, India
Walter J. McConathy
Department of Internal Medicine
University of North Texas Health Science
Center
Fort Worth, Texas
Scott E. McNeil
NCI Frederick
Frederick, Maryland
T. J. Miller
Center for Drug Evaluation and Research
Food and Drug Administration
Silver Spring, Maryland
Amitava Mitra
Department of Pharmaceutical Sciences and
Center for Nanomedicine and
Cellular Delivery
Baltimore, Maryland
S. M. Moghimi
Molecular Targeting and Polymer
Toxicology Group
School of Pharmacy
University of Brighton
Brighton, United Kingdom
Randall J. Mrsny
Center for Drug Delivery/Biology
Welsh School of Pharmacy
Cardiff University
Cardiff, United Kingdom
R. S. R. Murthy
Pharmacy Department
The M.S. University of Baroda
Vadodara, India
Natarajan Muthusamy
Columbus, Ohio
Anjan Nan
Department of Pharmaceutical Sciences and
Center for Nanomedicine and
Cellular Delivery
Baltimore, Maryland
Maya Nair
Departments of Molecular Biology and
Immunology
University of North Texas Health
Science Center
Fort Worth, Texas
Norased Nasongkla
Medical Center
Dallas, Texas
David Needham
Department of Mechanical Engineering
and Materials Science
Duke University
Durham, North Carolina
Tooru Ooya
Department of Materials Science
Japan Advanced Institute of Science
and Technology
Tatsunokuchi, Ishikawa, Japan
Jong-Sang Park
Department of Chemistry and Molecular
Engineering
Seoul National University
Seoul, South Korea
N. Sadrieh
Center for Drug Evaluation and Research
Food and Drug Administration
Silver Spring, Maryland
Kinam Park
Biomedical Engineering
Purdue University
West Lafayette, Indiana
Sanjeeb K. Sahoo
Nebraska Medical Center
Omaha, Nebraska
and
Institute of Life Sciences
Bhubaneswar, India
Tae Gwan Park

Department of Biological Sciences
Korea Advanced Institute of Science and
Technology
Daejeon, South Korea
Elamprakash N. Savariar
Anil K. Patri
NCI Frederick
Frederick, Maryland
Dinesh B. Shenoy
Boston, Massachusetts and Novavax, Inc.
Malvern, Pennsylvania
Ana Ponce
Department of Biomedical Engineering
Duke University
Durham, North Carolina
Patrick Lim Soo

Natalya Rapoport
Department of Bioengineering
University of Utah
Stephan T. Stern
Nanotechnology Characterization
Laboratory
NCI Frederick
Frederick, Maryland
Mike Andrew Rauth

L. Harivardan Reddy
Pharmacy Department
The M.S. University of Baroda
Vadodara, India
Fredika M. Robertson
College of Medicine and Comprehensive
Cancer Center
Columbus, Ohio
S. (Thai) Thayumanavan
Sandip B. Tiwari
Werner Tjarks
College of Pharmacy
Columbus, Ohio
Vladimir P. Torchilin
Anagha Vaidya
University of Utah
Geoffrey von Maltzahn
and Technology
S. P. Vyas
Dr. H. S. Gour University
Sagar, India
Sidney Wallace
Division of Diagnostic Imaging
The University of Texas M. D. Anderson
Cancer Center
Houston, Texas
Yanli Wang
University of Utah
Volkmar Weissig
Ho Lun Wong
Gong Wu
Columbus, Ohio
Xiao Yu Wu
Xiao-Bing Xiong
Faculty of Pharmacy and Pharmaceutical
Sciences
Weilian Yang
Columbus, Ohio
Furong Ye
University of Utah
Guodong Zhang
M. D. Anderson
Cancer Center
Houston, Texas
Xiaobin B. Zhao
Columbus, Ohio
.
Table of Contents
Section 1
Nanotechnology and Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Chapter 1
Introduction and Rationale for Nanotechnology

in Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Fredika M. Robertson and Mauro Ferrari

Chapter 2
Passive Targeting of Solid Tumors: Pathophysiological

Principles and Physicochemical Aspects of
Delivery Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
S. M. Moghimi
Chapter 3
Active Targeting Strategies in Cancer with a Focus on

Potential Nanotechnology Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Randall J. Mrsny
Chapter 4
Pharmacokinetics of Nanocarrier-Mediated
Drug and Gene Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Yuriko Higuchi, Shigeru Kawakami, and Mitsuru Hashida

Chapter 5
Multifunctional Nanoparticles for Cancer Therapy. . . . . . . . . . . . . . . . . . . . . . . 59
Todd J. Harris, Geoffrey von Maltzahn, and Sangeeta N. Bhatia

Chapter 6
Neutron Capture Therapy of Cancer: Nanoparticles

and High Molecular Weight Boron Delivery Agents. . . . . . . . . . . . . . . . . . . . . . 77
Gong Wu, Rolf F. Barth, Weilian Yang, Robert J. Lee, Werner Tjarks, Marina V. Backer, and
Joseph M. Backer
Chapter 7
Preclinical Characterization of Engineered Nanoparticles

Intended for Cancer Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Anil K. Patri, Marina A. Dobrovolskaia, Stephan T. Stern, and Scott E. McNeil

Chapter 8
Nanotechnology: Regulatory Perspective for Drug

Development in Cancer Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
N. Sadrieh and T. J. Miller
Section 2
Polymer Conjugates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Chapter 9
Polymeric Conjugates for Angiogenesis Targeted Tumor

Imaging and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Amitava Mitra, Anjan Nan, Bruce R. Line, and Hamidreza Ghandehari

Chapter 10
Poly(L-Glutamic Acid): Efficient Carrier of Cancer Therapeutics and

Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Guodong Zhang, Edward F. Jackson, Sidney Wallace, and Chun Li

Chapter 11
Noninvasive Visualization of In Vivo Drug Delivery

of Paramagnetic Polymer Conjugates with MRI. . . . . . . . . . . . . . . . . . . . . . . 201
Zheng-Rong Lu, Yanli Wang, Furong Ye, Anagha Vaidya, and Eun-Kee Jeong
Section 3
Polymeric Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Chapter 12
Polymeric Nanoparticles for Tumor-Targeted Drug

Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Tania Betancourt, Amber Doiron, and Lisa Brannon-Peppas

Chapter 13
Long-Circulating Polymeric Nanoparticles for Drug and

Gene Delivery to Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Sushma Kommareddy, Dinesh B. Shenoy, and Mansoor M. Amiji

Chapter 14
Biodegradable PLGA/PLA Nanoparticles for Anti-cancer

Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Sanjeeb K. Sahoo and Vinod Labhasetwar

Chapter 15
Poly(Alkyl Cyanoacrylate) Nanoparticles for Delivery

of Anti-Cancer Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
R. S. R. Murthy and L. Harivardhan Reddy

Chapter 16
Aptamers and Cancer Nanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Omid C. Farokhzad, Sangyong Jon, and Robert Langer

Section 4
Polymeric Micelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Chapter 17
Polymeric Micelles for Formulation of Anti-Cancer Drugs. . . . . . . . . . . . . . . 317
Helen Lee, Patrick Lim Soo, Jubo Liu, Mark Butler, and Christine Allen
Chapter 18
PEO-Modified Poly(L-Amino Acid) Micelles for

Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
Xiao-Bing Xiong, Hamidreza Montazeri Aliabadi, and Afsaneh Lavasanifar

Chapter 19
Hydrotropic Polymer Micelles for Cancer Therapeutics . . . . . . . . . . . . . . . . . 385
Sang Cheon Lee, Kang Moo Huh, Tooru Ooya, and Kinam Park
Chapter 20
Tumor-Targeted Delivery of Sparingly-Soluble Anti-Cancer

Drugs with Polymeric Lipid-Core Immunomicelles . . . . . . . . . . . . . . . . . . . . 409
Chapter 21
Combined Cancer Therapy by Micellar-Encapsulated

Drugs and Ultrasound. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
Natalya Rapoport
Chapter 22
Polymeric Micelles Targeting Tumor pH. . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
Eun Seong Lee and You Han Bae

Chapter 23
cRGD-Encoded, MRI-Visible Polymeric Micelles

for Tumor-Targeted Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
Jinming Gao, Norased Nasongkla, and Chalermchai Khemtong

Chapter 24
Targeted Antisense Oligonucleotide Micellar

Delivery Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
Ji Hoon Jeong, Sun Hwa Kim, and Tae Gwan Park

Section 5
Dendritic Nanocarriers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
Chapter 25
Dendrimers as Drug and Gene Delivery Systems . . . . . . . . . . . . . . . . . . . . . . 489
Tae-il Kim and Jong-Sang Park

Chapter 26
Dendritic Nanostructures for Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . . 509
Ashootosh V. Ambade, Elamprakash N. Savariar, and S. (Thai) Thayumanavan

Chapter 27
PEGylated Dendritic Nanoparticulate Carriers of

Anti-Cancer Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523
D. Bhadra, S. Bhadra, and N. K. Jain

Chapter 28
Dendrimer Nanocomposites for Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . 551
Lajos P. Balogh and Mohamed K. Khan

Section 6
Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593
Chapter 29
Applications of Liposomal Drug Delivery Systems

to Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595
Alberto A. Gabizon
Chapter 30
Positively-Charged Liposomes for Targeting

Tumor Vasculature. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613
Robert B. Campbell
Chapter 31
Cell Penetrating Peptide (CPP)Modified Liposomal

Nanocarriers for Intracellular Drug and Gene Delivery . . . . . . . . . . . . . . . . . 629
Chapter 32
RGD-Modified Liposomes for Tumor Targeting . . . . . . . . . . . . . . . . . . . . . . 643
P. K. Dubey, S. Mahor, and S. P. Vyas

Chapter 33
Folate Receptor-Targeted Liposomes for

Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 663
Xiaobin B. Zhao, Natarajan Muthusamy, John C. Byrd, and Robert J. Lee

Chapter 34
Nanoscale Drug Delivery Vehicles for Solid Tumors:

A New Paradigm for Localized Drug Delivery
Using Temperature Sensitive Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 677
David Needham and Ana Ponce
Section 7
Other Lipid Nanostructures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 721
Chapter 35
Nanoemulsion Formulations for Tumor-Targeted Delivery . . . . . . . . . . . . . . . 723
Sandip B. Tiwari and Mansoor M. Amiji

Chapter 36
Solid Lipid Nanoparticles for Antitumor Drug Delivery . . . . . . . . . . . . . . . . . 741
Ho Lun Wong, Yongqiang Li, Reina Bendayan, Mike Andrew Rauth, and Xiao Yu Wu
Chapter 37
Lipoprotein Nanoparticles as Delivery Vehicles

for Anti-Cancer Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 777
Andras G. Lacko, Maya Nair, and Walter J. McConathy

Chapter 38
DQAsomes as Mitochondria-Targeted Nanocarriers

for Anti-Cancer Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787
Shing-Ming Cheng, Sarathi V. Boddapati, Gerard G. M. DSouza, and Volkmar Weissig

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q 2006 by Taylor & Francis Group, LLC

q 2006 by Taylor & Francis Group, LLC

q 2006 by Taylor & Francis Group, LLC

q 2006 by Taylor & Francis Group, LLC

q 2006 by Taylor & Francis Group, LLC

q 2006 by Taylor & Francis Group, LLC

q 2006 by Taylor & Francis Group, LLC

Sang Cheon Lee

Tae Gwan Park

Patrick Lim Soo

Mike Andrew Rauth

q 2006 by Taylor & Francis Group, LLC

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