Wednesday, October 11
4:00-6:00pm Early Registration
Thursday, October 12
8:30 Chairperson’s Remarks
Chairperson: James L. Tatum, M.D., Special Assistant, Cancer Imaging Program, National Cancer Institute
8:40 Anti-bio Barrier Nanovector Technology
Mauro Ferrari, Ph.D., Professor, Brown Institute of Molecular Medicine, University of Texas Health Science Center; Professor of Experimental
Therapeutics, M.D. Anderson Cancer Center; and Professor of Biomedical Engineering, Rice University
A multiplicity of biological barriers combine to severely impair the time-honored strategy of improving the therapeutic index of anticancer drugs by their site-selective delivery, based on biological affinity recognition. These barriers comprise those of endothelial and epithelial nature, which are themselves comprise of multiple, sequential components, as well as the sequestration or degradation of the active or targeting moieties, and barriers associated with the driving forces in convective or diffusional mass transport. Nanotechnology offers an unprecedented opportunity to decouple the three major functions: cytotoxicity, selectivity, and the avoidance of biological barriers, by assigning the last two essentially to the vectoring component (the nanoparticle), as opposed to the active principle.
Introduction: Mr. Emery
Scheibert, President, Dendritech, Inc.
9:10 DNA-Linked Dendrimer Nanoparticle Systems for Cancer Diagnosis and Treatment
James R. Baker, Jr., M.D., Ruth Dow Doan Professor and Chief, Division of Allergy & Clinical Immunology; Director, Michigan
Nanotechnology Institute for Medicine & Biological Sciences
Dendritic polymer architecture allows for the development of new therapeutics that directly target cancer cells and largely bypass healthy cells. Clusters of these polymers can be combined into more complex structures with several different subunits, each with its own function, be it targeting, imaging or therapeutics. This technology can be expanded by developing single-function dendrimer modules linked by complementary oligonucleotides, thus producing multifunctional therapeutics that can be customized to a specific patient’s needs.
9:40 Development of Functionalized Nanoparticles for Early Detection and Treatment of Cancers and Metastatic Disease
Carola Leuschner, Ph.D., Pennington Biomedical Research Center, Baton Rouge
We have developed nanoparticles that specifically target LHRH receptors for specific delivery, higher efficiency and faster accumulation of nanoparticles within tumor cells. The nanoparticles are iron oxide based particles of less than 30 nm diameter, they are monodisperse, neutral of charge and have a high saturation magnetization. Surface modification allows binding of membrane disrupting peptides on these functionalized nanoparticles creating particles that enhance magnetic resonance imaging sensitivity in vivo and can at the same time destroy tumors and metastases.
10:10 Coffee Break, Poster & Exhibit Viewing
10:45 Targeted Nanoemulsions for Molecular Imaging and Therapy
Samuel A. Wickline, M.D., Professor of Medicine, Biomedical Engineering, Physics, and Cellular Biology, Washington University
We have developed perfluorocarbon nanoemulsions that can be molecularly targeted and imaged with MRI, nuclear, ultrasound, and CT methods. Furthermore these emulsions are biocompatible and can deliver large payloads of potent drugs and genes to specific cells. Dramatic augmentation of drug delivery with the use of exogenous energy (focused ultrasound at clinical frequencies and power) can facilitate local deposition of therapeutic agents while potentially limiting toxic side effects. These agents are poised to enter clinical trials as antiangiogenic agents targeted to endothelial integrins expressed on neovasculature in cancer, and as imaging agents for tracking the response to antiangiogenic therapy.
11:15 Nanodelivery: Materializing the Potential of Cancer Molecular Medicine
Esther H. Chang, Ph.D., Georgetown University Medical Center’s Lombardi Comprehensive Cancer Center
Many issues need to be addressed before the promise of tumor-targeting diagnosis and therapy for cancer can be realized. Foremost among these is the efficient and selective delivery of diagnostic and/or therapeutic molecules to the
site(s) in the body where the target tumor cells reside. Of particular relevance to cancer is the ability to target cells that have metastasized from the site of the primary tumor to distant sites in the body. Our laboratory has developed a platform nanotechnology comprising a cationic liposomal nanocomplex bearing molecules that home to the surface of tumor cells. When systemically administered, this tumor targeting nanocomplex can efficiently and selectively deliver not only nucleic acid-based therapeutics, but also diagnostic contrast agents and small molecules to primary tumors and metastases in animal models of a variety of human cancers. The nanodelivery of imaging agents results in a significant improvement in the sensitivity and resolution in detecting metastatic lesions. Moreover, the various nucleic acid-based therapeutics have been shown to dramatically synergize with conventional radio- and chemotherapies. This approach is now entering clinical trials.
11:45 Speaker Discussion
Chairperson: Mauro Ferrari, Ph.D.
• Issues Around Environment and Human Health
• Moving Nanoparticles Toward the Clinic
• Toxicity Issues
• Freedom to Operate Patent Issues
• Legal Issues and IP
Wendy R. Sanhai, Ph.D., Senior Scientific Advisor, Office of the Commissioner, Food and Drug Administration
Stephen B. Maebius, Partner, Foley & Lardner LLP
12:30 Lunch on Your Own (Luncheon Workshop
1:45 Chairperson’s Remarks
Chairperson: Piotr Grodzinski, Ph.D., Program Director for Cancer Nanotechnology, National Cancer Institute
1:50 Advances in Stealth Liposome Design and Surface Engineering: Overcoming Complement-Related Pseudoallergic Reaction
S. Moein Moghimi, Ph.D., Senior Lecturer, Molecular Targeting and Polymer Toxicology Group, School of Pharmacy and Biomolecular Sciences, University of Brighton
Intravenously injected poly(ethylene glycol)-grafted liposomes (PEGylated liposomes) exhibit prolonged circulation times in the blood. As a result of enhanced permeability retention phenomenon these liposomes can efficiently accumulate at well-perfused and low-pressure regions of solid tumours. In spite of the presence of the surface protective poly(ethylene glycol) chains, PEGylated liposomes have the ability to activate the complement system, and in sensitive individuals this could induce anaphylactic reactions. In view of the clinical importance of the observed complement-mediated hypersensitivity reactions, we have now determined structural features of PEGylated liposomes that are responsible for complement activation. Accordingly, novel non-complement activating phospholipid-methoxypoly(ethylene glycol) conjugates have been synthesized as a first critical step towards development of safer long circulating trigger release vesicles for in vivo applications.
2:20 Preclinical Characterization of Nanoparticles Intended for Clinical Applications
Scott McNeil, Ph.D., Director, Nanotechnology Characterization Laboratory
The National Cancer Institute’s (NCI) Nanotechnology Characterization Laboratory (NCL) conducts preclinical efficacy and toxicity testing of nanoparticles intended for clinical applications. The NCL is a collaborating partnership between NCI, the U.S. Food and Drug Administration and the National Institute of Standards and Technology. As part of its assay cascade, NCL characterizes nanoparticles’ physical attributes, their in vitro biological properties, and their in vivo compatibility using animal models.
2:50 3D Electron Microscopy in Nanobiology
Sriram Subramaniam, Ph.D., Senior Investigator, Laboratory of Cell Biology and Head, Biophysics Section, Center for Cancer Research, National Institutes of Health
Emerging methods in three-dimensional biological electron microscopy provide powerful tools and great promise to bridge a critical gap in imaging in the biomedical size spectrum. This gap, which comprises objects in the 10 nm to 1000 nm size range, includes cellular protein machines, viruses, small subcellular organelles and small bacteria and is of considerable interest in modern biology and medicine. I will review work in my laboratory on developing and applying novel 3D electron microscopic approaches for analysis of a variety of biological assemblies in this size range and discuss the relevance of these studies for nanoparticle standardization and localization.
3:20 Refreshment Break Poster & Exhibit Viewing
4:00 Adapting Nano-molding Techniques from the Microelectronics Industry for the Generation of Highly Versatile Shape-specific, Organic Nanoparticles for Targeted Delivery and Imaging Applications
Joseph M. DeSimone, Ph.D., Professor of Chemistry, University of North Carolina Chapel Hill
I will describe in this lecture our recently initiated studies for the detection, imaging and treatment of various disease states using harvested nano-scale, organic particles fabricated using techniques inspired by fabrication processes from the electronics industry. We believe there is a significant opportunity to precisely fabricate smart organic nano-particles, through the establishment of a Particle Foundry, with unprecedented levels of uniformity and capability using continuous mass production methods suitable for translational research.
4:30 Mathematical Design of NanoParticles for Cancer Imaging and Therapy
Paolo Decuzzi, Ph.D., Associate Professor, Center of BioNanotechnology and BioEngineering for Medicine, University of Magna Graecia
The power of intravascularly injectable particles over free molecules administration lies in their multifunctionality (carrying simultaneously contrast and therapeutic agents; controlled drug release; multiple ligands species) and engineerability (chemical, physical and geometrical properties can be tuned to improve avoidance of biophysical barriers and enhance target specificity). The talk will focus on the mathematical modeling of the interaction between a particle and a biological substrate, considering both specific interactions, mediated by ligand-receptor binding, and non-specific interactions mediated by van der Waals, steric and electrostatic forces. From these mathematical models, new strategies for the optimal design of nanoparticles are derived, regarding the size, the shape and the surface chemico-physical properties of the particle. The talk can be of interest to scientists involved in the development, fabrication and in-vivo/in-vitro application of nanoparticles for cancer imaging and therapy.
|5:00 Panel Discussion with Speakers:
Metrics for Standardization
• What procedure will be used to establish standards?
• How will it be enforced?
• What is the connection between metrics and safety?
Dr. Nakissa Sadrieh, Associate Director for Research Policy and Implementation, FDA/CDER/OPS
5:30 Networking Reception in the Exhibit Hall
6:30 Close of Day One