Curcumin Nanoparticles And Their Cytotoxicity In Docetaxel-Resistant Castration-Resistant Prostate Cancer Cells

Most prostate cancer patients develop resistance to anti-androgen therapy. This is referred to as castration-resistant prostate cancer (CRPC). Docetaxel (DTX) is the mainstay treatment against CRPC. However, over time patients eventually develop DTX resistance, which is the cause of the cancer-related mortality. Curcumin (CUR) as a natural compound has been shown to have very broad pharmacological activities, e.g., anti-inflammatory and antioxidant properties. However, CUR is very hydrophobic. The objective of this study was to develop CUR nanoparticles (NPs) and evaluate their cytotoxicity in DTX-resistant CRPC cells for the treatment of DTX-resistant CRPC. We tested solubility of CUR in different lipids and surfactants. Finally, Miglyol 812 and D-alpha-tocopheryl poly (ethylene glycol) succinate 1000 (TPGS) were chosen to prepare lipid-based NPs for CUR. We fully characterized CUR NPs that had particle size < 150 nm, high drug loading (7.5%), and entrapment efficiency (90%). Moreover, the CUR NPs were successfully lyophilized without using cryoprotectants. We tested the cytotoxicity of blank NPs, free CUR, and CUR NPs in sensitive DU145 and PC3 cells as well as their matching docetaxel-resistant cells. Cytotoxicity studies showed that blank NPs were very safe for all tested prostate cancer cell lines. Free CUR overcame the resistance in PC3 cells, but not in DU145 cells. In contrast, CUR NPs significantly increased CUR potency in all tested cell lines. Importantly, CUR NPs completely restored CUR potency in both resistant DU145 and PC3 cells. These results demonstrate that the CUR NPs have potential to overcome DTX resistance in CRPC.