Reduction‐Sensitive Polymeric Micelles Based on Docetaxel‐Polymer Conjugates Via Disulfide Linker for Efficient Cancer Therapy

In this article, the low‐molecular weight biodegradable methoxy poly (ethylene glycol)‐poly ( d , l ‐lactide‐co‐glycolide) (PP) is chosen as polymeric skeleton to be conjugated with docetaxel (DTX) by disulfide bond (PP‐SS‐DTX) to construct the reduction‐sensitive drug delivery system. The conjugates are synthesized via three steps and are further employed to physically load free DTX to develop the PP‐SS‐DTX/DTX micelles which exhibit many merits including high drug loading content, good stability, and stimuli‐sensitive release of drugs. The hydrodynamic diameter of PP‐SS‐DTX/DTX micelles determined by DLS is 112.3 nm. The hemolysis assay reveals the good blood compatibility of PP‐SS‐DTX/DTX micelles. In order to investigate the reductive sensitivity of PP‐SS‐DTX/DTX micelles, dithiothreitol (DTT) is added into the release medium and a programmed drug release mode is observed in the conjugated micelles. In vitro cytotoxity assay shows that the PP‐SS‐DTX/DTX micelles are more cytotoxic than that of free DTX solution for both MCF‐7 and B16F10 cancer cells. In addition, the PP‐SS‐DTX/DTX micelles also show a higher cellular uptake rate than that of free DTX. Hence, the prepared reduction‐sensitive PP‐SS‐DTX/DTX micelles are effective on inhibiting cancer cells compared with the free DTX which would be a promising carrier in cancer therapy. image