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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Blotting, Western
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Cations / chemistry
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Cell Line, Tumor
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Cell Proliferation
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Cholesterol / chemistry
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Cytoplasm / metabolism
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Drug Delivery Systems*
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Humans
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Liposomes*
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Microscopy, Electron, Transmission
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Neoplasms / genetics
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Neoplasms / therapy*
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Phagocytosis
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Phosphatidylethanolamines / chemistry
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Polymers / chemistry
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Polymers / pharmacology*
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RNA, Small Interfering / administration & dosage*
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RNA, Small Interfering / genetics*
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Vascular Endothelial Growth Factor A / antagonists & inhibitors
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Cations
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Liposomes
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Phosphatidylethanolamines
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Polymers
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RNA, Small Interfering
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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dioleoyl phosphatidylethanolamine
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Cholesterol