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.
See http://explore.georgetown.edu/people/change/?action=viewgeneral&PageTemplateID=208

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.
See http://nanomed.uth.tmc.edu/mferrari

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.
See http://www.chem.purdue.edu/people/faculty/faculty.asp?itemID=44

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.
See http://www.burnham.org/default.asp?contentID=209