Enhancement of gene therapy on hepatocellular carcinoma by sonoporation -- parameter studies

Ultrasound (US) is believed to be a novel and effective tool to locally deliver gene into target tumors. US can temporally change the permeability of cell membrane and thus enhance the delivery of naked DNA into cells. In this study, the gene transfection in tumor and muscle tissues was evaluated by changing the contrast agent concentrations and US exposure durations. The luciferase and IL-12 mixed with SonoVue^reg were injected intramuscularly (IM) or intratumorally (IT), followed by exposure to US of 20% in duty cycle and 2 W/cm² in intensity. The serum levels of IL-12 were determined by ELISA. Experimental results showed that both local and systemic expressions of the naked DNA in muscle are significantly higher than those in subcutaneous and liver tumors, and an order of muscle > subcutaneous tissue > liver tumor was found. Best transfection efficiency could be obtained by using 50% SonoVue in tumor and 30% in muscle after 10 min US exposure.