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  • Title: Reversal of lung cancer multidrug resistance by pH-responsive micelleplexes mediating co-delivery of siRNA and paclitaxel.
    Author: Yu H, Xu Z, Chen X, Xu L, Yin Q, Zhang Z, Li Y.
    Journal: Macromol Biosci; 2014 Jan; 14(1):100-9. PubMed ID: 23966347.
    Abstract:
    The recent advances in RNA interference (RNAi) technology provided novel and promising solutions for human cancer treatment. In this study, the application of dual pH-responsive cationic micellar nanoparticles for small interfering RNA (siRNA) and paclitaxel (PTX) co-delivery to overcome cancer multidrug resistance (MDR) is reported. The in vitro siRNA transfection shows that siRNA-luciferase (Luc) loaded micelleplexes efficiently silences Luc expression in various carcinoma cell lines. The Luc knockdown ability of the micelleplexes can be enhanced by choloquine (CQ) co-incubation. However, is abolished by bafilomycin-A1 (Baf-A1) treatment. The micelleplexes are further exploited for co-delivery of siRNA-Bcl-2 and PTX to Bcl-2 overexpressing A549 lung cancer cells (A549-Bcl-2). The experimental results show that the micelleplexes could sensitize A549-Bcl-2 cells to PTX via down-regulation of anti-apoptosis gene of Bcl-2, suggesting that PDMA-b-PDPA micelleplexes are promising nanovectors for siRNA and anti-cancer drug co-delivery to overcome cancer MDR.
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