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Nanobiology Is Taking Off at the CCR: The First Nanobiology Think Tank Held
In his opening remarks, Travis Earles of the NCI Alliance for Nanotechnology in Cancer provided a general introduction to nanotechnology as an important tool that promises to revolutionize cancer diagnosis and treatment and described several important areas of research, including nanotechnology-based imaging techniques and the development of multifunctional nanoparticles. He also emphasized the role of the alliance in helping to reduce the burden of cancer by accelerating the application of the best innovative nanotechnologies currently available. Dr. Blumenthal described the CCRNP as a program with a firm research foundation in mathematics, physics, chemistry, and biology and one with theoretical, experimental, and practical application to clinical settings and nanotechnologies. The CCRNP’s mission is to understand the structure and function of biomolecules and their assemblies and, based on the knowledge gained, to design nanodevices, including biologically based nanoparticles, for in vivo imaging, diagnosis, and targeted therapy for cancer, AIDS, and other viral diseases. This Nanobiology Think Tank is one of the several outreach programs of the CCRNP to promote collaborations, disseminate knowledge, and enhance the development of novel creative ideas for research and biomedical applications. After the opening remarks and introduction by Dr. Blumenthal, 20 speakers presented various aspects of their nanobiology-related research and development. To view the list of invited speakers, click here. Notably, in vivo experiments were described that could lead to nanodevices for clinical use. Linda Molnar, PhD (SAIC-Frederick, Inc.) provided a stimulating overview of nanotechnology and how NCI contributes to the realization of its full potential. She presented examples of successful nanotechnology-based approaches for in vivo imaging. Steven Libutti, MD (NCI) described a novel nanoparticle based on the conjugation of gold nanoparticles with tumor necrosis factor (TNF) that dramatically increases the TNF concentration in tumors compared with native TNF. He presented data for MC-38 tumor growth in C57BL/6 mice demonstrating 100% survival of mice treated with the nanoparticles compared with 60% survival of mice treated with native TNF. The nanoparticle formulation was found safe in rabbits and will be tested in a phase I clinical trial with 36 patients. Gregory Lanza, MD, PhD (Washington University) described several nanoparticle-based approaches and a large amount of data for in vivo imaging and treatment of tumors in mice and humans, as well as fibrin-targeted streptokinase nanoparticles that rapidly lyse thrombi. He demonstrated the superiority of targeted nanoparticles compared with those that are non-targeted. Anu Puri, PhD (NCI) presented very interesting data for nanoliposome-based, temperature-triggered release of fluorescent probes as imaged in mice and data demonstrating increased stability of liposomes in rats after appropriate modifications of the phosphatidylcholine sn-2 fatty acid carbonyl ester conferring resistance to phospholipase A2. King Li, MD, MBA (Clinical Center, NIH) emphasized the role of effective biodistribution of polymerized lipid and other nanoparticles for imaging and therapy. He presented amazing data for the use of pulsed high-intensity focused ultrasound to enhance delivery of nanoparticles in murine cancer models. Mark Kester, PhD (Penn State College of Medicine) demonstrated how nanoparticles help to solve problems with the systematic delivery of the chemotherapeutic agent ceramide, which is limited by its cell impermeability, metabolism, and precipitation. He presented data that showed encapsulation of ceramide (as well as siRNA) in nanoliposomes significantly enhances its therapeutic activity in mouse models of cancer. Another exciting area of research he described involved new nanoparticles called molecular dots, which are based on calcium phosphate matrix material, and their use for encapsulation of ceramide to treat tumors in mice. Mansoor Amiji, PhD (Northeastern University) described the use of nanoemulsions for image-guided murine cancer therapy and the delivery of paclitaxel across the blood-brain barrier in mice, as well as multifunctional nanocarriers against drug resistance in cancer. Oxana Pickeral, PhD, MBA (NCI) provided an overview of the Joint Division of Cancer Treatment and Diagnosis (DCTD)–CCR Early Therapeutics Development Program. She emphasized the new U.S. Food and Drug Administration (FDA) Exploratory IND (Investigational New Drug) Guidance issued in 2005 and the concept of phase 0 trials, which are intended to accelerate clinical development of new therapeutic and imaging agents. This is a unique co-development opportunity open to NCI researchers, academics, and business-sector collaborators, who can benefit from NCI’s deep expertise in developing anticancer agents and its greater tolerance of developmental risk compared with the commercial sector. Scott McNeil, PhD (SAIC-Frederick, Inc.) described the objectives of the Nanotechnology Characterization Laboratory, which are to identify and characterize critical parameters related to the biocompatibility and structure-activity relationships of nanomaterials, establish and standardize an assay cascade for nanomaterial characterization, examine the biological characteristics of multicomponent and combinatorial platforms, and engage in and facilitate academic and industrial-based education and knowledge sharing. He emphasized the preclinical characterization of nanoparticles and described various equipment and assays available in the laboratory, as well as data obtained with those assays. Stimulating discussions dominated the first Nanobiology Think Tank, reflecting an intellectual atmosphere that is fruitful with novel ideas and excitement for science. |
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realignment of the former Laboratory of Experimental and Computational Biology
to the first intramural Center for Cancer Research Nanobiology Program (CCRNP)
created much excitement and provided new opportunities for the development of
innovative approaches to the diagnosis and treatment of cancer. The excitement
was felt in the enthusiastic response to the first Nanobiology Think Tank, organized
by the Director of the CCRNP, Robert Blumenthal, PhD. The event, held on June
2 in Frederick, was attended by more than 100 participants from within and outside
the NIH.