title: Sterically polymer-based liposomal complexes with dual-shell structure for enhancing the siRNA delivery.
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.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China.
authors.forename: Shuian-Yin
authors.initials: SY
authors.lastname: Lin
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Zhao
authors.forename: Hsieh-Chih
authors.initials: HC
authors.lastname: Tsai
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Hsu
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Lo
authors.forename: Ging-Ho
authors.initials: GH
authors.lastname: Hsiue
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002784:Cholesterol / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D010587:Phagocytosis; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D002412:Cations; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011108:Polymers; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C094877:dioleoyl phosphatidylethanolamine; D002784:Cholesterol