报告人：Prof. Chun Wang
Department of Biomedical Engineering, University of Minnesota
题目：Polymeric Nanomaterials for Gene and Vaccine Delivery
Since the last decade, much progress has been made toward designing cationic polymeric gene carriers with high transfection efficiency and low cytotoxicity and in elucidating the relationship between polymer structure and gene delivery performance. However, delivery of gene-based vaccine to improve antigen presentation and immune activation poses unique challenges that have yet been fully addressed. Using well-defined copolymers of 2-aminoethyl methacrylate (PAEM) as models, we have shown that a chemically simple cationic polymer can have surprisingly high efficiency in transfecting dendritic cells (DCs), leading to antigen-presentation and T cell activation, but the mechanism behind in vitro and in vivo delivery is rather complex. Further, cellular stress responses (including apoptosis and autophagy) provoked by polyplexes and the timing of phenotypic maturation of DCs may be manipulated to improve transgene expression and cross-presentation of antigen. In addition to serving as models, the PAEM polymers may have the potential to be practically useful carriers of DNA vaccine in preventing and treating diseases.
To facilitate formulation and delivery of multi-component cancer vaccines, we have recently developed a new class of biodegradable semi-solid polymers (named Caproxamers?) that allows easy loading and controlled release of both hydrophobic and hydrophilic cargos. Subcutaneous injection of antigens and adjuvants formulated in an ortho-ester-containing Caproxamer induced antigen-specific antibody and T cell responses and showed therapeutic benefit in mice with orthotopic brain tumor. Combining simplicity in synthesis with versatility in properties, the potential use of the Caproxamers may go beyond vaccine delivery to include other drug delivery applications.
Chun Wang received his Ph.D. in Bioengineering with Jind?ich Kope?ek at the University of Utah. He was an NIH postdoctoral fellow with Robert Langer at the Massachusetts Institute of Technology, before joining the faculty of the University of Minnesota, where he currently is an Associate Professor in Biomedical Engineering with courtesy appointments in Chemical Engineering and Material Science and Pharmaceutics. He serves on the editorial board of the Journal of Controlled Release (since 2005) and Advanced Drug Delivery Reviews (since 2010). He was the recipient of the National Science Foundation CAREER Award, Wallace H. Coulter Foundation Early Career Translational Research Award, and McKnight Land-Grant Professorship. He has published over 50 peer-reviewed research articles and given over 80 invited talks. His research interests are polymer-based therapeutic biomaterials with applications in controlled drug delivery, immunotherapy, medical devices, and regenerative medicine.