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Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer model

Abstract

We have previously synthesized a new cationic liposome that displays high efficiency and low toxicity, 3β[l-ornithinamide-carbamoyl] cholesterol (O-Chol), using solid-phase synthesis. In this study, O-Chol was applied to in vitro and in vivo models of ovarian cancer. Intraperitoneal gene delivery for peritoneal disseminated ovarian cancer in nude mice was achieved using a stable chloramphenicol acetyl transferase (CAT)-expressing ovarian cancer cell line (OV-CA-2774/CAT), which allowed us to quantify the exact tumor burden of organs. When luciferase and β-galactosidase genes were used as reporter genes, O-Chol showed better efficiency than other commercial transfection reagents such as lipofectin, lipofectAMINE, DC-Chol, and FuGENE 6, both in vitro and in vivo. Moreover, the transfection efficiency of this new cationic lipid reagent remained high in serum-containing medium and under serum-free conditions. Furthermore, in vivo transfection with O-Chol showed high levels of gene expression specific to peritoneal tumor cells. Consequently, the O-Chol:DNA lipoplex appears to offer potential advantages over other commercial transfection reagents because of (1) its higher level of gene expression in vitro and in vivo; (2) its reduced susceptibility to serum inhibition; and (3) its highly selective transfection into tumor cells. These results suggest that the O-Chol:DNA lipoplex is a promising tool in gene therapy for patients with peritoneal disseminated ovarian cancer.

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Acknowledgements

We acknowledge the support of this work by the Brain Korea 21 program, the Korea Research Foundation, the Korea Science and Engineering Foundation, and the Korean Ministry of Health and Welfare (JS Park), and by the Korean Ministry of Health and Welfare (01-PJ1-PG1-01CH06-0003) and the Korea Science and Engineering Foundation SRC–Molecular Therapy Research Center, Sungkyunkwan University School of Medicine (DK Kim). We wish to thank Ms Jung-Eun Jang for her excellent technical assistance.

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Lee, MJ., Cho, SS., You, JR. et al. Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer model. Gene Ther 9, 859–866 (2002). https://doi.org/10.1038/sj.gt.3301704

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