This R21/R33 application entitled """"""""Nanoparticles for Harvesting and Targeting Angiogenic Proteins"""""""" has as its hypothesis that development and refinement of surface characteristics of silica chips with nanocharacteristics can enhance sensitivity of mass spectrometry (MS) detection of the low molecular weight angiogenic proteins present in serum and tumors that produced at very early times of tumor development. In addition, refinement of conjugation methods of nanoporous particles will allow selective targeting of endothelial cells in vitro and tumor-associated blood vessels in vivo and in combination with refinement of loading strategies, cytotoxic agents loaded into nanoparticles can selectively destroy these vessels. Our experimental plan is based on our expertise in development and refinement of emerging nanotechnology approaches for protein capture, for selective targeting and loading of silicon nanoparticles. These studies also take advantage of our experience in identification of novel proteins within the vascular endothelial growth factor (VEGF) family of proteins that are essential in the process of tumor-associated angiogenesis. To achieve the goal of developing and refining tools for detection of angiogenic proteins and for selective targeting and destruction of tumor-associated blood vessels, the following Specific Aims are proposed: 1. Develop and refine silica chips with nanocharacteristics to enhance the sensitivity of LC-MS/MS identification VEGF proteins in serum and in skin tumors during skin tumor-associated angiogenesis in vivo; 2. Refine conjugation of silicon nanoparticles to anti-VEGFR-2 receptor antibodies for selective targeting of endothelial cells in vitro and targeting tumor-associated blood vessels in vivo; 3. Determine the ability of silicon nanoparticles conjugated with anti-VEGFR-2 antibodies to be loaded with and to deliver the cytotoxic agent melatin for destruction of endothelial cells in vitro and for destruction of tumor-associated blood vessels in vivo. These studies will provide sensitive nanotechnology tools that are critical in defining the proteome in serum and tumors related to tumor angiogenesis that is currently unexplored. These studies may also provide strategies to selectively target tumor vessels for destruction using nanotechnology approaches. ? ? ?
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