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Reversal of Lung Cancer Multidrug Resistance by p H ‐ R esponsive Micelleplexes Mediating Co‐ D elivery of si RNA and Paclitaxel
Author(s) -
Yu Haijun,
Xu Zhiai,
Chen Xianzhi,
Xu Leilei,
Yin Qi,
Zhang Zhiwen,
Li Yaping
Publication year - 2014
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201300282
Subject(s) - small interfering rna , paclitaxel , gene knockdown , multiple drug resistance , transfection , rna interference , chemistry , a549 cell , cancer research , apoptosis , cancer cell , cationic liposome , drug resistance , cancer , pharmacology , rna , biology , biochemistry , microbiology and biotechnology , gene , genetics
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.