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  • Title: Folate-conjugated amphiphilic block copolymer micelle for targeted and redox-responsive delivery of doxorubicin.
    Author: Lv Y, Yang B, Li YM, He F, Zhuo RX.
    Journal: J Biomater Sci Polym Ed; 2018 Jan; 29(1):92-106. PubMed ID: 29090629.
    Abstract:
    In this paper, novel folate-conjugated and redox-responsive crosslinked block copolymer was successfully synthesized for targeted and controlled release of doxorubicin (DOX) to cancer cells. Folate-conjugated poly(ethylene glycol)-b-copolycarbonates (FA-PEG-b-P(MAC-co-DTC)) and methoxy poly(ethylene glycol)-b-copolycarbonates (mPEG-b-P(MAC-co-DTC)) were firstly synthesized by enzymatic method. FA-PEG/mPEG-b-P(MAC-co-DTC)-SS was then obtained by further crosslinking reaction with cystamine. Non-conjugated crosslinked copolymer mPEG-b-P(MAC-co-DTC)-SS- and non-conjugated uncrosslinked copolymer mPEG-b-P(MAC-co-DTC) were also synthesized for comparison. All the amphiphlic copolymers could self-assemble to form nano-sized micelles which dispersed in spherical shape before and after DOX loading. The core crosslinking structure of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS could improve the micellar stability and drug loading capacity, while in vitro release studies also showed more sustained drug release behavior which could be accelerated in reductive condition. Moreover, confocal laser scanning microscopy indicated that the conjugation of FA could enhance the cellular uptake efficiency obviously via FA-receptor-mediated endocytosis, and MTT assays demonstrated highly potent cytotoxic activity of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS.
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