Nanoscale Encasement and Targeted Delivery of Multifunctional Therapeutic Agents

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This team of investigators will develop novel multifunctional therapeutic and diagnostic agents encased in nanoscale delivery devices. The central goal of each project is to engineer and evaluate a variety of "smart" nanoscale cargo bins (nanobins) that can target cancer cells, bind to them and subsequently unload up to more 500000 molecules of a cytotoxic or radiopharmaceutical agents. The synthetic nanofabrication group will make new bioconjugates of monoclonal antibodies and test their efficacy in collaboration with clinicians who use antibodies now in cell culture assay and in the clinic. The approach will combine new loading strategies for established anticancer drugs (O'Halloran) with theoretical approaches (Schatz) to design novel liposomes, advanced lipid precursors technology for the synthesis of articulated liposomes (MacDonald), development of polymer micelle technology (Nguyen), nanofabrication methods for polymer cylinders (Odom). Each of these agents will initially be evaluated in collaboration with the clinical groups (Singhal, Tallman, Rosen) in cell culture models for leukemia and multiple myeloma. Specific agents will also be evaluated in solid tumor models. The proposed 'Nanobin' cargo systems can also house biological agents, peptides, enzymes and growth-inhibiting factors that impact a tumor and/or its immediate microenvironment. These new materials thus have the potential of providing sustained therapy for cancers that must be treated chronically.