NER: Neovasculature-Targeted Biogenic Magnetic Nanoparticles

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0508535PengThis proposal was received in response to Nanoscale Science and Engineering initiative, NSF 04-043, category NER.In this proposed project, targeted delivery of functionalized biogenic magnetic nanoparticles to avB3 integrin-bearing tumor cells followed by hyperthermia treatment will be studied. Since magnetic nanoparticles can be excited by external alternating electromagnetic field and used as hyperthermia agents, targeting magnetic nanoparticles to endothelial cells via avB3 integrin may provide an effective means to disrupt the growth of new blood vessels by toxic amounts of thermal energy and thereby lead to malignant cell destruction. In addition, according to published accounts, shortened circulatory half-lives of therapeutic nanoparticles in the bloodstream (ingested by mononuclear phagocyte system) prevent sufficient nanoparticles from reaching the target cells. To mitigate phagocytosis of nanoparticles, the applicantproposes to incorporate the "marker of self" integrin-assocaited protein (CD47) on the surface of biogenic magnetic nanoparticles extracted from magnetotactic bacteria. In addition to its antiphagocytic feature, CD47 protein conjugated with magnetic nanoparticles will act as a ligand targeted for avB3-integrin expressing cells. In summary, the proposed CD47-conjugated magnetic nanoaprticles are expected to have much extended half-lives in blood circulation, hence allowing for more efficient site binding via integrin avB3 and inducing thermal destruction of tumor neovasculature by exciting site-targeted magnetic nanoparticles with electromagnetic energy.