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

Gene Therapy volume 8, pages 1276–1280 (2001)Cite this article

Abstract

We investigated the transfection efficiency of β-sitosterol β-D-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), 3β[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.

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Acknowledgements

We would like to thank Prof T Tsuji and his research group at the Department of Microbiology of Hoshi University for assistance in plasmid preparation and Associate Prof J Kamei and his research group at the Department of Pharmacology of Hoshi University for assistance in luciferase assay. We also would like to thank Dr J Wang for assistance in the experimental work. This work was supported in part by the Tokyo Nagai Foundation and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan, 12672210.

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Authors and Affiliations

  1. Department of Pharmaceutics, Hoshi University, Shinagawa-ku, Tokyo, Japan

    SH Hwang, K Takayama & Y Maitani

  2. Department of Virology, Toyama Medical and Pharmaceutical University, Toyama, Japan

    K Hayashi

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  1. SH Hwang
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  2. K Hayashi
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  3. K Takayama
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Hwang, S., Hayashi, K., Takayama, K. et al. Liver-targeted gene transfer into a human hepatoblastoma cell line and in vivo by sterylglucoside-containing cationic liposomes. Gene Ther 8, 1276–1280 (2001). https://doi.org/10.1038/sj.gt.3301510

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