Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model.

OBJECTIVE

In order to increase local drug concentration and reduce systemic side effects of liver cancer chemotherapy, it is desirable to develop novel non-invasive technologies for drug targeting, such as ultrasound-targeted microbubble destruction (UTMD).

METHODS

H22 hepatocellular carcinoma (HCC) xenograft transplantation model was generated in UTMD study. BALB/c mice were randomly divided into six groups: doxorubicin HCl liposomal injection (DOX), DOX + US, UTMD, DOX + UTMD, H22 liver tumor control (CH control) and blank control group. The therapeutic schedule started on day 4 after tumor inoculation.

RESULTS

Average survival time of the animal model was approximately 18 d. The UTMD therapy parameters were optimized in the H22 mouse model to be: microbubble (MB) diameter, 2.30 ± 0.25 μm; MB density, 4.0 × 10(9) bubbles/ml; treatment dose, 0.2 ml per 20 g mouse body weight; sonication frequency, 1.3 MHz; and sonication power, 2.06 W/cm(2). Mice treated with DOX + UTMD had the smallest tumor volume and weight (p < 0.001), and the highest tumor inhibition rate (p < 0.01), intratumoral DOX concentration (p < 0.001) and survival rate among all tumor-burden groups (p < 0.001). Cell viability in different treatment groups was also assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

CONCLUSION

An improved antitumor effect was observed with the combination therapy of DOX and UTMD, as compared with treatment with DOX, DOX + US or UTMD, which implicates a novel approach for HCC treatment.