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- W2912902889 abstract "Liposomes have emerged as a fascinating nanocarriers for the delivery of cancer therapeutics. However, their efficacy for cancer therapy is reduced partially because of the serum-instability and incomplete drug release. In this study, a novel disulfide cross-linked liposomes (CLs) assembled from dimeric lipoic acid-derived glycerophosphorylcholine (di-LA-PC) conjugate was developed. The conjugate was synthesized by a facial esterification of lipoic acid (LA) and glycerophosphorylcholine (GPC) and characterized by MS, 1H NMR and 13C NMR. Featuring the enhanced serum-stability and intracellular drug release determined by in vitro stability and GSH-responsive behavior, CLs prepared with dried thin film technique following 10 % dithiothreitol (DTT) cross-linking can attain effective delivery of anticancer candidates. Notably, CLs stably encapsulated doxorubicin (Dox) in their vesicular structures and showed a remarkable thiol-sensitive release of payload upon cellular uptake by cancer cells, compared to that of uncross-linked liposomes (uCLs) or Doxil-like liposome (DLLs). The cell viability and apoptosis of Dox-loaded CLs worked the pronounced cytotoxic effects to MCF-7 cells with an IC50 value of 10.8 μg Dox equiv./mL comparable to free Dox and 2.8-fold higher than DLLs. More importantly, it is demonstrated that the nanoscale characteristics of Dox-loaded CLs could prevent the proliferation of adriamycin-resistant MCF-7/ADR cell line, highlighting their potential in reversal of drug resistance. Furthermore, the preliminary in vivo test (n = 3) showed that disulfide cross-linked liposomal formulation of Dox (Dox-CLs) improved the therapeutic efficacy compared to free Dox and DLLs in a human breast carcinoma xenograft mouse model. Therefore, the current thiol-responsive cross-linked liposome may provide a robust drug delivery platform for cancer therapy." @default.
- W2912902889 created "2019-02-21" @default.
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- W2912902889 date "2019-04-01" @default.
- W2912902889 modified "2023-10-15" @default.
- W2912902889 title "Lipoic acid-derived cross-linked liposomes for reduction-responsive delivery of anticancer drug" @default.
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- W2912902889 doi "https://doi.org/10.1016/j.ijpharm.2019.02.007" @default.
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