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- W2564967520 abstract "Antibody-maytansinoid conjugates (AMCs) have emerged as one of the most promising active targeting cancer therapeutics. Their clinical use is, however, challenged by their low drug content, poor stability, high cost and potential immune response. Here, we designed and developed robust, cRGD-functionalized, reduction-sensitive polymeric micellar mertansine (DM1) prodrug (cRGD-MMP) that showed targeted treatment of B16F10 melanoma-bearing C57BL/6 mice. cRGD-MMP was obtained with a superb drug content of ~ 40 wt.% and a small size of ~ 45 nm from poly(ethylene glycol)-b-(poly(trimethylene carbonate)-graft-SSDM1) (PEG-P(TMC-g-SSDM1)) and cRGD-functionalized PEG-P(TMC-g-SSDM1) copolymers. cRGD-MMP exhibited excellent stability in 10% fetal bovine serum and cell culture medium while fast swelling and markedly accelerated drug release under a reductive environment. Confocal microscopy, flow cytometry and MTT assays indicated receptor-mediated uptake and high antitumor effect of cRGD-MMP in αvβ3 integrin over-expressing B16F10 melanoma cells. Notably, cRGD-MMP displayed a long elimination half-life of 5.25 h and 4-fold better maximum-tolerated dose than free DM1. The in vivo studies demonstrated that cRGD-MMP effectively inhibited B16F10 melanoma growth and greatly improved mice survival rate as compared to free DM1 and non-targeted MMP control. cRGD-MMP with superior stability, drug loading, and αvβ3 targetability offers an attractive alternative to AMCs for malignant tumor therapy." @default.
- W2564967520 created "2017-01-06" @default.
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- W2564967520 date "2017-08-01" @default.
- W2564967520 modified "2023-10-15" @default.
- W2564967520 title "αvβ3 Integrin-targeted reduction-sensitive micellar mertansine prodrug: Superb drug loading, enhanced stability, and effective inhibition of melanoma growth in vivo" @default.
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- W2564967520 doi "https://doi.org/10.1016/j.jconrel.2016.12.011" @default.
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