Sterically polymer-based liposomal complexes with dual-shell structure for enhancing the siRNA delivery |
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Authors: | Lin Shuian-Yin Zhao Wei-Yu Tsai Hsieh-Chih Hsu Wei-Hsin Lo Chun-Liang Hsiue Ging-Ho |
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Affiliation: | Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China. |
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Abstract: | The sterically polymer-based liposomal complexes (SPLexes) were formed by cationic polymeric liposomes and pH-sensitive diblock copolymer were studied for their capabilities in improving the stability with high efficiency of siRNA delivery. The SPLexes were formed a dual-shelled structure and uniform size distribution. The PEGylated outer shell could mitigate the phagocytosis and reduce the cytotoxicity. Moreover, the folated SPLexes improved 42.9× accumulation in vitro and 1.7× tumor uptake in vivo in contrast with nonfolated SPLexes. The protonated copolymer at low pH would improve the siRNA released into cytoplasm following SPLexes fusion with the endo/lysosome membrane and inhibited the protein expression to 75.6 ± 4.5% efficiently. Results of this study significantly contribute to efforts to develop lipoplexes based siRNA delivery systems. |
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