Selective gene expression in hepatic tumor with trans-arterial delivery of DNA/liposome/transferrin complex.
Since hepatocellular carcinoma (HCC) is frequently presented at an advanced stage, only a small portion of patients with HCC can be treated with local modalities. Gene therapy is, therefore, one of the more promising approaches for patients with advanced HCC. To develop a new strategy for targeting gene delivery to the hepatic tumor, the efficiency of the transarterial delivery of liposome-DNA complex was evaluated in VX2 carcinoma implanted into the liver of rabbits. A mixture of pSV-beta galactosidase plasmid (40 micrograms), lipofectin (80 microliters), and transferrin (852 micrograms), the optimal proportion of which determined in vitro, was infused via the hepatic artery of a rabbit with VX2 hepatic tumors. The efficiency of trans-arterial gene delivery was compared to that of intra-tumoral injection. Rabbits (5 in each group) were sacrificed 48 hours after gene delivery and hepatic tissues were examined using X-gal staining. beta-galactosidase staining was observed exclusively within the tumor following the trans-arterial gene transfer. In contrast, adjacent peritumoral cells in addition to hepatic tumor cells were transfected by the intra-tumoral injection of transgene. These data indicate that enhanced gene expression in hepatic tumors is possible using trans-arterial delivery of the liposome-DNA complex.
Seol
J G
JG
Cancer Research Center, Seoul National University College of Medicine, Korea.
Heo
D S
DS
Kim
H K
HK
Yoon
J H
JH
Choi
B I
BI
Lee
H S
HS
Kim
N K
NK
Kim
C Y
CY
D000818:Animals; D002461:Cell Line, Transformed; D017690:Cell Transplantation / Q000379:methods; D004247:DNA / Q000235:genetics*; D004337:Drug Carriers; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008081:Liposomes; D008099:Liver / Q000166:cytology* / Q000648:ultrastructure; D008114:Liver Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy; D011817:Rabbits; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D014162:Transfection / Q000379:methods*; D014168:Transferrin / Q000235:genetics*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
D004337:Drug Carriers; D008081:Liposomes; D011994:Recombinant Proteins; D014168:Transferrin; D004247:DNA; D001616:beta-Galactosidase