Liver-targeted gene transfer into a human hepatoblastoma cell line and in vivo by sterylglucoside-containing cationic liposomes

被引:36
作者
Hwang, SH
Hayashi, K
Takayama, K
Maitani, Y
机构
[1] Hoshi Univ, Dept Pharmaceut, Shinagawa Ku, Tokyo 142, Japan
[2] Toyama Med & Pharmaceut Univ, Dept Virol, Toyama, Japan
关键词
cationic liposome; sterylglucoside; liver target; Tfx-20; DC-Chol; gene transfer; serum;
D O I
10.1038/sj.gt.3301510
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the transfection efficiency of beta -sitosterol beta -glucoside (Sit-G)-containing liposome/DNA complex (Sit-G-liposome/DNA complex) for liver targeting. The Sit-G-liposome/DNA complex was composed of Tfx-20 reagent (Tfx), ie synthetic cationic lipid [N,N,N',N'-tetramethyl-N,N'-bis(2-hydroxyethyl)-2,3-di(oleoyloxy)-1,4-butanediammonium iodide] with L-dioleoylphosphatidylethanolamine (DOPE), 3 beta [N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) and Sit-G with plasmid DNA. The in vitro studies were performed in HepG2 cells in serum-containing medium and the in vivo studies were carried out in the mice following intravenous injection. The Sit-G-liposome produced a Sit-G-liposome/DNA complex of relatively small size (100-250 nm). Transfection efficiency of the luciferase marker gene by Sit-G-liposome/DNA complex was increased in the presence of 10% serum in vitro, and was selectively high in the mouse liver reaching expression values up to an average of 14.9 pg luciferase/mg tissue protein, compared with Tfx/DNA complex, which showed approximately three-fold higher gene expression than Sit-G-liposome/DNA complex in vitro. High in vitro transfection efficiency by Sit-G-liposome/DNA complex seemed to be possible even with large lipid precipitates, whereas high in vivo activity seemed to be related to small and dispersed complexes. The interaction of liposome/DNA complexes with serum may be a key point to predict the in vivo efficiency of a liposome vector.
引用
收藏
页码:1276 / 1280
页数:5
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