Huan Xie, Nanoformulation Development of a Novel Prostrate Cancer Inhibitor
Prostate cancer is the second leading cause of cancer death in the United States among men and it is more common in African American males. Normal prostate growth and maintenance is dependent on androgens acting through the androgen receptor (AR). AR expression is maintained and plays an important role throughout prostate cancer progression. The tetratricopeptide repeat (TPR) protein FKBP52 is a specific positive regulator of AR. Dr. Cox’s group has recently identified and characterized a series of small molecules that specifically inhibit FKBP52-mediated potentiation of AR signaling and target the AR binding function 3 (BF3) surface. The most promising compound, MJC13 (currently patent pending), has been shown to effectively block AR-dependent gene expression in cellular models of prostate cancer at low micromolar concentrations. It is a very attractive novel anticancer drug with great potential. However, the water solubility of this compound is very low and formulation is required to achieve higher bioavailability and better targeting to the prostate tumor site. Therefore, we propose to develop a novel multifunction nanoformulation for MJC13 by utilizing stealth liposomes to encapsulate the compound for much higher bioavailability and prolonged circulation as well as gold nanorods (GNRs) to remotely trigger liposomes disruption by near-infrared (NIR) light and release MJC13 upon arrival at the target site.