Antiangiogenic gene therapy on hepatocellular carcinoma using endostatin and sonoporation in vivo

Antiangiogenic gene therapy is a promising approach to inhibit neovascularization via angiogenesis, the growth of new blood vessels from pre-existing ones. In recent years, hepatocellular carcinoma (HCC) is considered as one of the suitable targets for antiangiogenic approaches due to its high neovascularization. On the other hand, ultrasound (US) is believed to be a novel and effective tool to locally deliver gene into target tumors. US can temporarily change the permeability of cell membrane and thus enhance the delivery of naked DNA into cells. In this study, the efficiency of gene transfection in tumor was compared by changing the US contrast agent (UCA) concentration and sonication time. Luciferase and enhanced green fluorescent protein (EGFP) plasmids mixed with SonoVue^® were injected intratumorally (IT), and US was applied at 20% duty cycle and 2 W/cm² in intensity. Finally, the efficacy of employing US to deliver genes encoded with an antiangiogenic factor, endostatin (ED), to suppress the growth of a preclinical HCC, which was inoculated subcutaneous (SC) tumor model, is evaluated. Our results show that weekly intratumoral injection group led to a 74% inhibition in HCC growth. In summary, the present study revealed the efficacy of US as a nonviral technology to efficiently deliver genes to tumors by weekly IT treatment approach, and to deliver angiogenic inhibitors to HCC in particular.