The main problem with traditional chemotherapeutic agents is their poor selectivity for cancer cells and their severe toxicity to normal cells. To overcome these issues, we intend to develop a tumor-selective drug delivery system where we modify the surface of Cytochrome c (Cyt c), an apoptosis initiating protein, with vitamins specific to receptors over expressed on cancer cells. Because Cyt c is a membrane impermeable protein, its intracellular delivery should be by receptor-mediated endocytosis. In theory, this can be accomplished by attaching a tumor-specific ligand. We chose folic acid (FA) as ligand to modify Cyt c because the folate receptor is over expressed in a wide variety of human tumors while its distribution in normal tissue is highly restricted. Folate-targeted small molecule toxin drugs are in clinical trials. We will expect that if properly modify Cyt c with folic acid, could selectively initiate apoptosis in these cells while not affecting healthy cells. For instance, the targeted delivery to cancer cells of a folate receptor targeted Cyt c could prove to be an effective neoplasmic agent with few side effects; making this approach an attractive cancer therapeutic strategy.

Folate receptor targeted Cytochrome C mediate cancer cell death

245th National Meeting (2013)

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