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Anionic Polymer Coating Enhance the RNAi Efficiency of Non-Viral Carriers in Serum Containing Environment |
Wang Jing, Xie Lifei, Meng Jie, Liu Jian#*, Xu Haiyan#* |
(Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College, Beijing 100005, China) |
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Abstract The clinical application of cationic polymer carriers was limited because the adsorption of protein in serum environment led to low transfection efficiency. In this work, we synthesized carboxylic Dextran (Dex-COOH) and water-soluble carboxylic fullerene (C60-Dex-COOH) anionic polymers, coated on the pullulan-spermine and siRNA complex (PS/siRNA) to reduce the adsorption of serum protein. The particle size and Zeta potential were analyzed by DLS/ELS, respectively. The formation of anion coating and bovine serum albumin (BSA) adsorption of complexes were tested by QCM-D. Cellular uptake, cytotoxicity on the Hela cells and RNAi efficiency on the Hela-EGFP cells were examined by cck-8 reagent and flow cytometry. The results showed that Dex-COOH and C60-Dex-COOH could coat on PS/siRNA to form stable electronegative complexes, prevent the adsorption of serum effectively. Cytotoxicity of complexes was reduced in the absence of serum. On the other hand, in the serum environment, anionic polymer coated complexes could help complexes enter cells and PS/siRNA@C60-Dex-COOH with visible light irradiation would escape from the lysosome, increased the interference efficiency by 20% compared with PS/siRNA. In summary, this coating strategy provided an effective solution of increasing RNAi efficiency mediated by cationic polymers.
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Received: 21 March 2016
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