Selective gene transfer to hepatocellular carcinoma using homing peptide-grafted cationic liposomes.
Gene delivery that provides targeted delivery of therapeutic genes to the cells of a lesion enhances therapeutic efficacy and reduces toxic side effects. This process is especially important in cancer therapy when it is advantageous to avoid unwanted damage to healthy, normal cells. Incorporating cancer-specific ligands that recognize receptors overexpressed on cancer cells can increase selective binding and uptake and, as a result, increase targeted transgene expression. In this study, we investigated whether a peptide capable of homing to hepatocellular carcinoma (HCC) could facilitate targeted gene delivery by cationic liposomes. This homing peptide (HBP) exhibited selective binding to a human hepatocarcinoma cell line, HepG2, at a concentration ranging from 5 to 5,000 nM. When conjugated to a cationic liposome, HBP substantially increased cellular internalization of plasmid DNA to increase transgene expression in HepG2 cells. In addition, there was no significant enhancement in gene transfer detected for other human cell lines tested including THLE-3, AD293, and MCF-7 cells. Therefore, we demonstrate that HBP provides targeted gene delivery to HCC by cationic liposomes.
Tu
Ying
Y
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Kim
Ji-Seon
JS
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000235:genetics* / Q000628:therapy*; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis
D008081:Liposomes; D010455:Peptides; D004247:DNA