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  • Title: Reduction-Sensitive Polymeric Micelles Based on Docetaxel-Polymer Conjugates Via Disulfide Linker for Efficient Cancer Therapy.
    Author: Guo Y, Zhang P, Zhao Q, Wang K, Luan Y.
    Journal: Macromol Biosci; 2016 Mar; 16(3):420-31. PubMed ID: 26647779.
    Abstract:
    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.
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