Cationic liposome-mediated gene delivery to the liver and to hepatocellular carcinomas in mice

The potential of cationic liposomes as nonviral vectors for in vivo gene de livery to the liver and to intrahepatic hepatocellular carcinoma (HCC) was investigated. Mice were injected via the tail vein or portal vein with a ca tionic lipid complexed to plasmid DNA (pDNA) encoding the chloramphenicol a cetyltransferase (CAT) reporter gene at various cationic lipid:pDNA molar r atios to analyze the efficiency of gene delivery after intravenous administ ration. Tail vein injection resulted in high CAT expression levels in lung and spleen and low levels in the liver. Portal vein injection, by compariso n, significantly enhanced hepatic reporter gene expression but also resulte d in pronounced hepatic toxicity. Gene delivery to intrahepatic tumors prod uced by intrahepatic injection of human HCC cells was analyzed in nude mice . Tail vein injection as well as portal vein injection resulted in low leve ls of gene expression in intrahepatic tumors. By comparison, high levels of gene expression were achieved by direct, intratumoral injection of liposom e-pDNA complexes, with only minimal expression in the surrounding normal li ver. Therefore, direct liposome-pDNA complex injection appears far superior to systemic or portal intravenous administration for gene therapy of local ized intrahepatic tumors, and may be a useful adjunct in the treatment of h uman HCCs.