VEGF-Based Delivery of Boron Therapeutics
70733S02-II 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 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 targeted delivery of non-toxic boron-10 (10B) to the tumor vasculature. When the site is irradiated with low-energy neutrons, they will be captured by the 10B atoms, which will undergo nuclear fission and yield high-energy products that destroy cells. Phase I constructed and tested in vitro assembled nanovehicles for boron-10 delivery. These nanovehicles carried a high capacity polymeric carrier for boron-10 that allows a Â¿loadingÂ¿ of 1120 boron atoms per every targeted molecule. The assembled nanovehicles were shown to be non-toxic, capable of binding to cellular receptors of vascular endothelial growth factor, and internalized by targeted cells. Phase II will test assembled targeted nanovehicles in animal tumor models. Novel, high capacity assembled nanovehicles will be constructed that combine imaging and therapeutic capabilities. Commercial Applications and Other Benefits as described by awardee: Targeted boron-10 therapeutics may provide an attractive alternative to highly toxic systemic chemotherapy and radiotherapy of cancer.
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