Co‐delivery of docetaxel and retinoic acid by poly (ethylene glycol)‐retinoic acid conjugates based micelles for synergistic prostate cancer therapy

Abstract

In the present work, docetaxel (DTX) and retinoic acid (RA) co-loaded micelles were developed for synergistic prostate cancer therapy. PEG-RA and RA-PEG-RA were synthesized and subsequently used for loading of DTX and RA. The as prepared DTX/RA@RA-PEG-RA micelles exhibit smaller size and higher drug loading capacity as compared to DTX/RA@PEG-RA micelles. The in vitro drug release study shows that DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles exhibit similar drug release behaviours in which DTX exhibits fast release and RA exhibits sustained release. Nile red (NR) was loaded into PEG-RA and RA-PEG-RA micelles to investigate the cellular uptake of the micelles by fluorescence microscope and flow cytometry. The results show that NR@RA-PEG-RA micelles exhibit slightly enhanced cellular uptake as compared to NR@PEG-RA micelles. The cellular uptake of DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles determined by HPLC also show similar results. In in vitro cytotoxicity against C4-2 and 22Rv1 cells, DTX in combination with RA exhibit synergistic antitumor effect, and DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles exhibit enhanced cytotoxicity against C4-2 cells and similar cytotoxicity against 22Rv1 cells as compared to DTX/RA. DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles show significant potential for prostate cancer therapy.