Metallated DNA Aptamers for Prostate Cancer Treatment.

摘要

The purpose of this project is to develop DNA aptamer complexes that are selectively cytotoxic to PSMA+ prostate cancer (PCa) cells. Our studies showed Zn2+ is cytotoxic to prostate cancer cells and also sensitizes PCa cells to chemotherapy. We developed a new DNA motif for Zn2+ delivery. We also developed a new chemical strategy for delivering the cytotoxic drug doxorubicin to cancer cells. We have demonstrated that our novel dimeric aptamer complexes are selectively internalized by PSMA+ prostate cancer cells and have demonstrated selective cytotoxicity with delivery of doxorubicin. We also developed a new nanoparticle (NP) composed of porphyrin and DNA and demonstrated that this NP was cytotoxic to bladder cancer cells in vitro, was non-toxic in vivo, and displayed strong anti-tumor activity in vivo. The aptamer complexes and the NPs we developed in this project are highly selective and highly active agents that have the potential to markedly improve chemotherapy for treatment of advanced prostate cancer.