Nanomedicine and nanotechnology research at the NIBIB and the NIH

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Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 2 (2006) 269–312

Dr. 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. Amiji is the Associate Chairman of Pharmaceutical Sciences Department and Co-Director of Northeastern University Nanomedicine Education and Research Consortium (NERC). NERC oversees a doctoral training program in Nanomedicine Science and Technology that is co-funded by the NIH and NSF. He has two published books, Applied Physical Pharmacy (McGraw-Hill, 2003) and Polymeric Gene Delivery: Principles and Applications (Taylor & Francis, 2005) and a third book Nanotechnology for Cancer Therapy will be published in 2006, along with numerous manuscripts and abstracts. Dr. Amiji has received a number of awards including the 2006 NSTI Award for Outstanding Contributions towards the Advancement of Nanotechnology, Microtechnology, and Biotechnology.

doi:10.1016/j.nano.2006.10.099

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Sunday, September 10th (2:25) Concurrent Symposium XVII: Neurology Nanomedicine

Bioengineering instructive cellular nanoenvironments Semino CE, Center for Biomedical Engineering, Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA Our motivation is the development of functional and instructive bioengineering cellular nanoenvironment with control of the physical, mechanical and chemical parameters for biomedical applications. Nanofiber network scaffolds—mainly hydrogels—are a good option for tissue engineering applications including the in vitro development of functional 3-dimensional (3D) tissue constructs. We have successfully used self-assembly peptide solutions that gel to form a nanofiber scaffold offering control over some physical, mechanical as well as chemical properties for cells and stem cell maintenance and differentiation. This 3D-culture system has been used to obtain stem cell differentiation down to hepatic, neuronal and osteogenic lineages, as well as maintenance of aortic endothelial phenotype promoted by the additional instructed chemical capacity rationally integrated into the scaffold. Moreover, we extended the use of these bio-inspired nanofiber scaffolds for long-term maintenance of hepatocyte metabolic functions, for toxicology applications in Pharmaceutical Industry. In a project more related to Nanomedicine, we are currently designing and testing a nanocomposite material composed of nanocarriers (for drug delivery) into a nanofiber scaffold for specific application in spinal disk regeneration. This project is part of an undergoing collaboration with the new established Translational Centre for Regenerative Medicine in Leipzig University, Germany. Dr. Semino (B.S. in Genetics and Molecular Biology, and Ph.D. in Chemistry) has served as a scientist at MIT in Douglas Lauffenburger’s Biological Engineering Division and MIT’s Center for Cancer Research, and Phylonics Pharmaceuticals. Dr. Semino is currently a scientist at the Center for Biomedical Engineering, MIT, an Associate Professor at the Barcelona Bioengineering Center, Department of Industrial Engineering, University Ramon Llull, Barcelona, Spain, where he teaches and directs undergraduate and graduate research programs in the area of cellular bioengineering. He recently joined the new Translational Centre for Regenerative Medicine at Leipzig University, Germany, as a visiting professor, to develop bioengineering application in the area of therapeutic medicine. His research is focus on cellular self-

organization and function, design of cell instructive microenvironments, and regenerative biology. doi:10.1016/j.nano.2006.10.100

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Sunday, September 10th (2:50) Concurrent Symposium XVII: Neurology Nanomedicine

The extracellular matrix: amyloidosis, tissue engineering and regenerative medicine Sipe JD, Musculoskeletal Tissue Engineering Study Section, Center for Science Review/NIH, Bethesda, Maryland, USA Each of the 20–30 chemically distinct types of amyloid deposits contains a common set of extracellular matrix constituents and non-fibril forming proteins. In particular, the proteoglycan components of the extracellular matrix, serum amyloid P component, apolipoprotein E and lipids influence protein unfolding and refolding in tissues undergoing amyloid deposition. Of the tens of thousands of proteins encoded within the human genome, fewer than thirty are known to share the feature of being susceptible to increased folding of the polypeptide backbone into the beta sheet conformation and extracellular assembly into amyloid fibrils. Each fibril forming protein is associated with a clinically distinct amyloid disease or disorder, including Alzheimer’s disease and other brain disorders, adult onset (type II) diabetes mellitus, plasma B-cell dsycrasias, long term hemodialysis, hereditary polyneuropathies and hereditary periodic fever syndromes. Outside the body, using denautring conditions that alter protein folding, amyloid fibrils have been created from many more than 30 proteins; this is an indication of the key role of the local tissue environment in triggering amyloid fibril formation within the body. The extracellular matrix is a key scientific factor in the grant applications reviewed by the Musculoskeletal Tissue Engineering Study Section [MTE], which evaluates applications focus on the replacement or repair of damaged, missing or poorly functioning musculoskeletal tissues, including bone, skeletal muscle, cartilage, tendon and ligament. The review of grant applications that are submitted to the National Institutes of Health (NIH) will be discussed. The unique, dual nature of the NIH peer review process will be described. The procedure for assignment of applications to study sections for evaluation of scientific and technical merit and to funding institutes for consideration of making grant awards will be presented. Pitfalls to be avoided in the preparation of NIH grant applications will be discussed. Jean D. Sipe earned her Ph.D. in Chemistry from the University of Maryland in 1971. After a brief period in private industry, she worked at the National Institutes of Health (NIH) studying the inflammation associated amyloid A precursor protein, serum amyloid A (SAA). In 1980 she moved to Boston University School of Medicine, where she continued studies on SAA and was promoted to Professor of Biochemistry in 1991. In 1997 Dr. Sipe returned to the NIH to the Center for Scientific Review to serve as a Scientific Review Administrator (SRA) of what is now the Musculoskeletal Tissue Engineering Study Section. doi:10.1016/j.nano.2006.10.101

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Sunday, September 10th (3:15) Concurrent Symposium XVII: Neurology Nanomedicine

Nanomedicine and nanotechnology research at the NIBIB and the NIH Heetderks W, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland, USA Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing

Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 2 (2006) 269–312 damaged tissues. Nanomedicine is a focus area of the NIH roadmap. Four nanomedicine development centers at UCSF, Baylor, Columbia and the University of Illinois have been established by the nanomedicine roadmap workgroup at NIH in areas from protein folding to cell motility. Competition is currently underway for 3–4 additional centers. Besides the nanomedicine initiative, NIBIB has developed a research portfolio in nanotechnology supporting research ranging from molecular imaging agents to nanotechnology for gene and drug delivery. This talk will review the ongoing research at the Institute in nanomedicine and nanotechnology. Dr. William J. Heetderks is the Director of Extramural Science Programs at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH. Before joining NIBIB he was at the National Institute of Neurological Disorders and Stroke (NINDS). At the NINDS he worked on and later led the Neural Prosthesis Program and was the scientific team leader for the Repair and Plasticity Cluster. He received undergraduate and masters degrees in Electrical Engineering and received the Ph.D. degree in Bioengineering all from The University of Michigan. He then joined the faculty in Electrical Engineering at Cornell University working in the areas of neural coding of information and digital signal processing. He received the MD degree from the University of Miami and is certified in Internal Medicine. He has received several awards including the NINDS Merit Award, the NIH Directors Award, The University of Michigan Distinguished Alumni Award in Bioengineering, and the Alfred Mann Foundation Award for Scientific Achievement. The mission of the NIBIB is to improve human health by leading the development and accelerating the application of biomedical technologies. The extramural program supports approximately 800 research and training grants at universities and research centers throughout the United States. doi:10.1016/j.nano.2006.10.102 92

Sunday, September 10th (3:40) Concurrent Symposium XVII: Neurology Nanomedicine

Nano neuro knitting: using nanotechnology to repair the brain Ellis-Behnke R, Massachusetts Institute of Technology, Boston, Massachusetts, USA Nanotechnology is often associated with materials fabrication, microelectronics, and microfluidics. Until now, the use of nanotechnology and molecular self assembly in biomedicine to repair injured brain structures has not been explored. In order to achieve axonal regeneration after injury in the central nervous system several formidable barriers must be overcome, such as scar tissue formation after tissue injury; gaps in nervous tissue formed during phagocytosis of dying cells after injury and the failure of many adult neurons to initiate axonal extension. Using the mammalian visual system as a model, we report that a designed self-assembling peptide nanofiber scaffold creates a permissive environment not only for axons to regenerate through the site of an acute injury, but also to knit the brain tissue together. In experiments using a severed optic tract in the hamster, we show that regenerated axons reconnect to target tissues with sufficient density to promote functional return of vision, as evidenced by visually elicited orienting behavior. The peptide nanofiber scaffold not only represents a new nanobiomedical technology for tissue repair and restoration, but also raises the possibility of effective treatment of central nervous system and other tissue or organ trauma. Dr. Rutledge Ellis-Behnke is a neuroscientist at M.I.T. and the University of Hong Kong Medical Faculty who uses nanobiotechnology to reconnect disconnected parts of the brain. He received his PhD from MIT, BS from Rutgers and graduated from Harvard Business School’s Int’l Senior Manager’s Program. Prior to earning his PhD, he was co-founder/CEO of

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the first company selling computer memory online and SVP of Huntingdon, a public testing and consulting firm. Memberships include Amer. Acad. of Nanomedicine, NY Academy of Sciences, China Spinal Cord Injury Network, Soc. for Neuroscience, Assoc. for Research in Vision and Ophthalmology, American Soc. for Neurochemistry and Sigma Xi. doi:10.1016/j.nano.2006.10.103 93

Sunday, September 10th (2:00) Concurrent Symposium XVIII: Oncology and Experimental Nanomedicine

Nanotechnology for cancer diagnostics and therapeutics Heller M, Heller MJ, Department of Bioengineering/Electrical, University of California San Diego, San Diego, California, USA, Department of Computer Engineering, University of California San Diego, San Diego, California, USA The recent formation of an NCI Center for Cancer Nanotechnology at UCSD has accelerated the research and development on a number of nanotech based approaches for cancer diagnostics and therapeutics. One of the goals that is the focus of our research group is the development of a cancer therapy monitoring/diagnostic platform device. Such a device is intended to provide near real time monitoring of patient blood for cancer cells, cell derived nanoparticulates (such as high molecular weight DNA fragments), and also carry out subsequent cancer related genotyping, gene expression and immunochemical analysis. Key to success for such a device is the development of a miniaturized dielectrophoretic (DEP) blood separation/ analysis unit, a nanopore DNA isolation component, and a nanopore DNA sizing/genotyping component which incorporates ultra-sensitive FRET quantum dot detection. Such a system would allow very small quantities of patient blood to be shunted into a sample chamber where cells and serum would be processed by a dielectrophoretic (DEP) microarray. This unit would rapidly remove blood cells from serum, and have the capability to isolate tumor cells and cell-derived micro/nanoparticulates. HMW DNA fragments in the serum would be separated by an electric field nanopore separation unit. The Isolated DNA fragments would then be labeled and the molecular weight rapidly determined by nanopore electrophoresis. Michael J. Heller — Ph.D., Biochemistry, Colorado State University, 1973, NIH Postdoctoral Fellow; Northwestern University, 1973 –1976. Supervisor, DNA Technology Group, Amoco Corporation, 1976 – 1984; Director Molecular Biology, Molecular Biosystems, 1984 – 1987; Co-Founder, President and COO, Integrated DNA Technologies, 1987 – 1989; Co-founder and CTO, Nanogen, Inc., San Diego, CA, 1993 – 2001. Now Professor, Departments of Bioengineering and Electrical and Computer Engineering, University California San Diego. Extensive experience, and numerous patents and publications in areas of biotechnology; DNA probe diagnostics, fluorescent detection, microelectronic DNA arrays and nanotechnology. Also, served on several review panels for the National Nanotechnology Initiative. doi:10.1016/j.nano.2006.10.104 94

Sunday, September 10th (2:25) Concurrent Symposium XVIII: Oncology and Experimental Nanomedicine

Nanocomposite labeling and selective destruction of cells using Laser Induced Optical Breakdown (LIOB) Balogh LP, Nair BM, Kariapper MST, Lesniak W, Khan MK, Tse C, Zohdy MJ, Ye J, Norris T, O’Donnell M, NanoBiotechnology Center at Roswell Park Cancer Institute (NBC at RPCI), Buffalo, New York, USA, Biomedical Engineering, Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, Michigan, USA