VEGF-Based Delivery of Boron Therapeutics
70733 Because the growth of primary tumor and metastatic lesions beyond a few millimeters requires formation of new blood vessels (angiogenesis), the targeted delivery of cytotoxic drugs to growing tumor blood vessels may form the basis for a highly selective anti-cancer therapy. Particularly attractive are two-step therapies that initially deliver relatively non-toxic Â¿prodrugsÂ¿ that are subsequently activated at the sites of angiogenesis. This project will develop a two-step therapy that relies on the highly targeted delivery of non-toxic boron-10 (10B) containing polymers to growing endothelial cells at the sites of angiogenesis. Upon irradiation with low-energy neutrons, 10B atoms capture them, undergo nuclear fission, and yield high-energy products that destroy cells. Phase I will construct and test in vitro nanovehicles for boron-10 delivery that are targeted by the highly specific vascular endothelial growth factor. These nanovehicles will carry a high capacity cargo module containing a polymeric carrier for boron-10. The cargo module will be non-covalently docked to a specialized Â¿docking tagÂ¿ engineered into vascular endothelial growth factor. Commercial Applications and Other Benefits as described by the awardee: Targeted boron-10 therapeutics may provide an attractive alternative to highly toxic systemic chemo- and radiotherapy of cancer.
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