Codelivery of miR-4638-5p and Docetaxel Based on Redox-Sensitive Polypeptide Micelles as an Improved Strategy for the Treatment of Castration-Resistant Prostate Cancer.

ABSTRACT

In this work, we have developed a reducible, self-assembling disulfide cross-linked and peptide-based micelle system for codelivery of miR-4638-5p and DTX to improve the efficacy of castration-resistant prostate cancer (CRPC) therapy. The result showed that DTX in micelles (DTX-VPs) inhibited cell growth and induced apoptosis more effectively than free DTX both in vitro and in vivo. In addition, the DTX and miR-4638-5p loaded micelles (Co-VPs) achieved the most pronounced anticancer effect of all groups. Immunohistochemical analysis indicated that miR-4638-5p in micelle system could effectively downregulate the expression of Kidins220 and further improve the anticancer effect by enhancing tumor cell apoptosis and suppressing tumor cell proliferation. Finally, the bioimaging analysis demonstrated that DIR in micelles (DIR-VPs) showed a higher concentration and a longer retention time in tumor tissue than did free DIR, which indicated an excellent tumor-targeting ability of the micelle system. All these results suggest that codelivery of miR-4638-5p and DTX via polypeptide micelle system has a potential for CRPC treatment.