Experimental study on targeted ultrasound contrast agent in the gene therapy of liver cancer

Abstract

Objective To develop a novel approach of transfecting the objective gene tagetedly mediated by ultrasound contrast agent conjugated ligand of hepatocyte with ultrasound irradiation.Methods C-myc ASODN and galactosylation polylysine which was specific ligand of hepatocyte and the surface of SonoVue microbbule were coupled by electrostatic interaction.Liver cancer cells SMMC-7721 and lung cancer cells A-549 were transfected with c-myc ASODN in vitro by ultrasound-mediated microbubble destruction.The c-myc gene expression of SMMC-7721 cells and A-549 cells was detected by semiquantitative RT-PCR.Results Ultrasound mediated microbubble destruction can enhance antisense c-myc gene expression in SMMC-7721 cells and A-549 cells.C-myc expression was decreased in transfected SMMC-7721 cells with G-PLL(P＜0.01).C-myc expression in A-549 cells with G-PLL was similar to without G-PLL(P＞0.05).Conclusions Ultrasound mediated microbubble destruction method can enhance gene transfection,ultrasound and hepatocellular receptor-mediated microbubble destruction have target to liver cells,in which the gene expression level was increased.It is a promising method in gene therapy of liver cancer. Key words: Ultrasonography; Microbubbles; Gene therapy; Liver neoplasms