title: 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, 3 beta[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 beta-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.
authors.affiliation: School of Chemistry, Seoul National University, Seoul, South Korea.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Lee
authors.forename: S-S
authors.initials: SS
authors.lastname: Cho
authors.forename: J-R
authors.initials: JR
authors.lastname: You
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.forename: B-D
authors.initials: BD
authors.lastname: Kang
authors.forename: J S
authors.initials: JS
authors.lastname: Choi
authors.forename: J-W
authors.initials: JW
authors.lastname: Park
authors.forename: Y-L
authors.initials: YL
authors.lastname: Suh
authors.forename: J-A
authors.initials: JA
authors.lastname: Kim
authors.forename: D-K
authors.initials: DK
authors.lastname: Kim
authors.forename: J-S
authors.initials: JS
authors.lastname: Park
mesh_terms: D000818:Animals; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007274:Injections, Intraperitoneal; D008081:Liposomes / Q000008:administration & dosage*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000556:secondary* / Q000628:therapy; D010714:Phosphatidylethanolamines; D012190:Retroviridae / Q000235:genetics; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D008081:Liposomes; D010714:Phosphatidylethanolamines; D008156:Luciferases; D001616:beta-Galactosidase