Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer model.
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.
Lee
M-J
MJ
School of Chemistry, Seoul National University, Seoul, South Korea.
Cho
S-S
SS
You
J-R
JR
Lee
Y
Y
Kang
B-D
BD
Choi
J S
JS
Park
J-W
JW
Suh
Y-L
YL
Kim
J-A
JA
Kim
D-K
DK
Park
J-S
JS
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
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D008081:Liposomes; D010714:Phosphatidylethanolamines; D008156:Luciferases; D001616:beta-Galactosidase