Innovative Drug Discovery and Nanotechnology
(Track) XPCLAD NANOREFORMULATION OF CISPLATIN FOR PROSTATE CANCER James W. Lillard Jr, Shailesh Singh, and Rajesh Singh Morehouse School of Medicine, 720 Westivew Drive SW, Atlanta, GA 30310 Abstract: We determined the utility of cisplatin-loaded biodegradable XPclad nanoparticles coated with folate-conjugated polycaprolactone-polyethylene glycol. Prostate cancer (PCa) cell lines, but not normal prostatic epithelial cells, expressed high levels of folate receptor a (FRa/FR1). Similar to cancer cells, Treg cells but not T helper cells express high affinity folate receptor (FRd/FR4). Treatment using 20 μM of cisplatin solution resulted in > 90% cell death of PCa cells, PrEC, and RWPE-1 cells as well as purified Tregs and T helper cells. However, XPclad nanoparticles, containing cisplatin (0.2 µM), were taken up and induced the same level of apoptosis in PCa cells as cisplatin solution, but did not significantly affect normal cells. Similar selective killing of Tregs, but not T helper cells, were noted after XPclad nanoparticle treatment of tumor-bearing mice. PC3 tumor-bearing mice that received either cisplatin (8 mg/kg/week) or cisplatin-encapsulated folate-coated XPclad nanoparticles (0.08 mg/kg/week) resulted in significant tumor regression. Mice receiving cisplatin solution had significantly higher kidney and liver toxicities than XPclad nanoparticle-treated mice. Our studies show XPclad nanoparticles enhance cisplatin activity without toxicity and suggest FR-targeted nanotherapy is selective for prostate tumor cells and Treg cells for increased efficacy of cytotoxic cancer drugs. |