Targeted Delivery of Therapeutic Oligonucleotides for the Treatment of Prostate Cancer
Annual rept. 1 May 2002-30 Apr 2003
PITTSBURGH UNIV PA
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Down-regulation of Bcl-2 expression via antisense oligodeoxynucleotides ODN may show promise as a novel therapy for the treatment of prostate cancer. The success of the antisense therapy is largely dependent on the development of a vector that is highly efficient in selective delivery of ODN to prostate cancer cells. To this end we have developed a novel lipid vector that is highly efficient in encapsulating ODN. Using folate as a model ligand we have shown that incorporation of folate into the lipid vector resulted in a significant improvement in intracellular delivery of ODN to KB cells that overexpress folate receptors. Targeted delivery of an EGFR antisense ODN via the novel lipid vector led to a dramatic reduction in the EGFR expression in KB cells. In a separate study we have shown that a small molecule glutamate carboxypeptidase inhibitor DBetaE efficiently mediates liposomal targeting to LNCaP prostate cancer cells that overexpress prostate specific membrane antigen PSMA. These studies pave the way for the future development of PSMA-specific lipid vectors to selectively deliver Bcl-2 antisense ODN to prostate cancer cells.
- Medicine and Medical Research