Targeted Delivery of Therapeutic Peptides by Genetically Engineered Biopolymers

University Of Mississippi Medical Center, Jackson MS

Investigators

Abstract

0931041 Raucher The goal of this project is to develop targeted therapeutic carriers for the treatment of solid tumors. Targeted drug delivery increases the specificity and efficacy of cancer therapy and thus reduces damage to normal tissues that is associated with conventional chemotherapy. The proposed carrier is a genetically-engineered, thermally responsive polypeptide that inhibits the proliferation and growth of cancer cells. The amino acid sequence of the polypeptide carrier is based on elastin-like biopolymers that are soluble below 37 degree celsius, but aggregate at temperatures above 41 degree celsius. This characteristic can be exploited to thermally target the drug carrier to the solid tumor site. In addition to the elastin-like polypeptide carrier, the drug delivery vehicle is genetically engineered to contain a short peptide, Bactenecin, that facilitates cell entry, and a peptide derived from the cyclin-dependent kinase inhibitor p21, which inhibits the cell cycle and cell growth. By applying local heat to solid tumors, these polypeptides can be targeted to and accumulate at the tumor site, inhibiting cancer cell growth. To address this hypothesis, the following specific aims will be addressed: 1) measure the plasma kinetics and in vivo distribution of the drug in normal and cancerous tissue and 2) evaluate the therapeutic efficacy of this drug in the treatment of ovarian tumors in mice through repeated administration of the agent when the tumor is heated and unheated. This research will provide the in vivo data necessary to move this therapy towards the translational stage of human therapeutics. In order to fulfill these scientific aims, a highly structured program will be created to recruit undergraduate students, especially minorities and members of underrepresented groups, to this collaborative research endeavor. The state of Mississippi has the largest percentage population of African American citizens of any state in the United States, yet remains well below national and southern state averages in enrollment of African American students into and graduation from doctoral programs within the state. Active research experience is one of the most effective ways to attract talented undergraduates to and retain them in careers in research and medicine. Therefore talented undergraduate students will be recruited from Tougaloo College and will participate directly in the creation of this drug delivery vehicle and in the implementation of the specific aims of this project.