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  • Title: Folate-conjugated amphiphilic block copolymers for targeted and efficient delivery of doxorubicin.
    Author: Lv Y, Yang B, Jiang T, Li YM, He F, Zhuo RX.
    Journal: Colloids Surf B Biointerfaces; 2014 Mar 01; 115():253-9. PubMed ID: 24370849.
    Abstract:
    In this paper, novel biodegradable amphiphilic block copolymers based on 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 successfully synthesized for targeted and efficient delivery of doxorubicin (DOX) to cancer cells. Immobilized porcine pancreas lipase (IPPL) was employed as the catalyst to perform the ring-opening copolymerization in bulk, while the folate-conjugated poly(ethylene glycol) (FA-PEG) or methoxy poly(ethylene glycol) (mPEG) was used as the initiator. The resulting copolymers, characterized by (1)H NMR and GPC, could self-assemble to form nano-sized micelles in aqueous solution by dialysis method. P(MAC-co-DTC) acted as the hydrophobic core, thereby aggregating hydrophilic PEG chains as the outer shell with FA as targeting ligand located at the surface of the polymeric micelles. Transmission electron microscopy (TEM) observation showed that the micelles dispersed in spherical shape with nano-size before and after DOX loading. Both the FA-conjugated and non-conjugated block copolymers showed low cellular cytotoxicity. Furthermore, as compared to the non-conjugated copolymers, much more efficient cellular uptake of the FA-conjugated copolymers via FA-receptor-mediated endocytosis could be observed by confocal laser scanning microscopy (CLSM), while MTT assays also demonstrated highly potent cytotoxic activity against HeLa cells.
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