5th Annual Cancer Nanobiology Think Tank
Date: June 3, 2010
Location: Bldg. 549 Auditorium, National Cancer Institute, Frederick, MD
Theme: Nanoparticles for Tumor Targeting
Organizers: Robert Blumenthal and Jacek Capala
Center for Cancer Research Nanobiology Program (CCRNP) pursues an integrated, multidisciplinary program of basic and applied studies aimed at the design of nanodevices to combat cancer, AIDS and other viral diseases. Steps to achieve the goal involve:
- To understand the structure and function of biomolecules and their assemblies at the nanoscale
- To understand engineering principles of Nano machineries used in living cells
- Use this knowledge to build multifunctional devices for preventing and curing disease
Nanobiology offers many new exciting approaches to the problems of diagnosing, preventing and curing cancer and other
diseases. It also offers alternative ways to think about issues relating to disease detection, i.e. biosensors.
Nanobiology brings together diverse multidisciplinary research groups to solve problems that are associated with
nanodesign. In order to establish and strengthen lines of communication between multidisciplinary researchers from
CCR and the intramural and extramural communities we have organized annual Nanobiology think tank workshops at
NCI-Frederick for the past five years. The aim is to discuss nanotechnology-, nanobiology-, and nanomedicine-related
issues and become more informed about current research and future developments in these fields. These one-day workshops
organized are organized along a particular theme in Nanobiology.
For 2010 we have centered the workshop on the theme of Nanoparticles for Tumor Targeting. In particular, we plan to focus
the discussion on the benefit of adding targeting molecules to the nanoparticle platforms. The tumor-specific delivery of
diagnostic and therapeutic agents by nanoparticles is crucial for their successful application. One of the most unique
characteristics of nanoparticles is their "spontaneous" accumulation in the tumor tissue due to the imperfections of
tumor blood vessels leading to enhanced permeability and retention effect. In addition, the nanoparticles can be conjugated
with targeting agents binding specific receptors on cells within the tumor volume. Several types of molecules might be
used for this purpose including antibodies, antibody fragments, Affibody molecules, aptamers, peptides, sugars, and natural
or modified ligands. Such modification may increase the retention and, in some cases, facilitate internalization of
nanoparticles. On the other hand, high affinity of targeting agents may make the nanoparticles “sticky” and prevent their
diffusions through the tumor parenchyma. The 5th Annual Cancer Nanobiology Think Tank will be devoted to discussions
regarding the optimization of nanoparticles for tumor-specific delivery of diagnostic and therapeutic agents. Different
tumor-targeting strategies and their effect on the biodistribution of nanoparticles and their load will be discussed
following expert presentations of the relevant data. For the 5th Annual Cancer Nanobiology Think Tank, we have invited
speakers who will bring their expertise to bear on the various facets of this theme. Their presentations will be followed
by brainstorming sessions focused around the talks, discussions, and questions that arise. Participants are encouraged to
submit abstracts related to the theme of the think tank and they will have the opportunity to present their studies in
poster sessions during the day. A few contributions from these submissions will be selected for short (5 min) oral
presentations during the brainstorming sessions. The invited speakers are:
Esther H. Chang, Ph.D. Departments of Oncology and Otolaryngology, Lombardi Comprehensive Cancer Center of Georgetown
University Medical Center, Georgetown University, Washington, DC
Dr. Chang's research interest include tumor suppressor gene therapy for cancer; tumor-targeted liposome-based systemic
gene delivery modulation of oncogene expression by sequence-specific antisense oligonucleotides; and molecular basis of cancer.
Mauro Ferrari, Ph.D. Professor & Chairman, Department of Nanomedicine & Biomedical Engineering; Professor of Internal Medicine,
Division of Cardiology, The University of Texas Health Science Center; Professor of Experimental Therapeutics, The University
of Texas, M.D. Anderson Cancer Center; Professor of Bioengineering, Rice University; and President, Alliance for NanoHealth, Houston, TX
Dr. Ferrari is an internationally recognized expert in the development, refinement and application of biomedical nanotechnology.
Dr. Ferrari's group employs methods of semiconductor nanotechnology and mathematical modeling to develop solutions to problems
in molecular medicine, with particular interest in applications in oncology and cardiology. He is regarded as a pioneer in the
fields of BioMEMS, biomedical nanotechnology, and multi-scale mathematics. Among his many 'firsts' are: silicon-based
nanochannel technology, with its applications to controlled release drug delivery and immunoprotected cell transplantation;
multistage particulates for drug delivery; the rational design of nanovectors; and nanotextured chips for the selective
enrichment of the plasma peptidome for early detection of pathological states.
Philip S. Low, Ph.D. Purdue University, Lafayette, IN
Dr. Low's research is focusing on two areas that stem from a basic interest in membrane structure and function.
The first project is focused on the study of the function and molecular organization of the human red blood cell
membrane. Included in this research are projects aimed at characterizing: (1) the interactions between the
membrane and its underlying cytoskeleton; (2) the signal transduction pathways that control cell shape and flexibility;
(3) the crystallographic structure of important membrane proteins; and (4) the changes in membrane architecture
that trigger unwanted red cell adhesion. A second research thrust focuses on the use of targeting ligands to
deliver covalently attached therapeutic and imaging agents specifically to pathologic tissues for medical purposes.
Because the receptor for the ligand, folic acid, is measurably overexpressed by activated macrophages (but no other
hematopoietic cells) and many types of human cancers, Dr. Low's group is attaching folic acid to: (1) radioimaging
agents; (2) chemotherapeutic drugs; (3) gene therapy constructs; (4) liposomes with encapsulated drugs; (5) protein
toxins; (6) immunotherapeutic agents; (7) radiotherapeutic complexes; (8) MRI contrast agents; (9) nanoparticles;
(10) optical imaging agents; (11) oligonucleotides; and (12) various therapeutic proteins in order to facilitate
their binding and uptake by both activated macrophages and cancer cells.
Erkki Ruoslahti, Ph.D, M.D. Burnham Institute for Medical Research at UCSB, Santa Barbara, CA
The underlying themes of Dr. Ruoslahti's work are tumor vasculature and metastasis. Tumors, like other tissues, contain both
blood vessels and lymphatic vessels. A tumor needs blood vessels to be able to grow, and destroying tumor blood vessels is
the basis of a promising new cancer therapy. Lymphatic vessels are not needed for tumor growth, but like blood vessels,
the lymphatics are an important conduit of distant metastasis. Dr. Ruoslahti's research interests include: (1) screening
of large collections ("libraries") of random peptides to identify those that bind to specific targets in the vasculature
(vascular zip codes); (2) use of homing peptides as targeting elements to deliver nanoparticles into tumors and other sites
of disease; and (3) signaling pathways that control anoikis (cell death caused by lack of attachment), and through it
metastasis and even angiogenesis.