Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity.
Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and beta-galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.
Aoki
K
K
Section for Studies on Host-Immune Response, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan.
Furuhata
S
S
Hatanaka
K
K
Maeda
M
M
Remy
J S
JS
Behr
J P
JP
Terada
M
M
Yoshida
T
T
D000818:Animals; D004247:DNA / Q000493:pharmacokinetics; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000556:secondary* / Q000628:therapy; D011094:Polyethyleneimine; D016133:Polymerase Chain Reaction; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D005819:Genetic Markers; D008081:Liposomes; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases; D001616:beta-Galactosidase