Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model |
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Authors: | Fangyu Zhu Yong Jiang Pan Li |
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Affiliation: | 1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China and;2. Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China |
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Abstract: | 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?×?109 bubbles/ml; treatment dose, 0.2?ml per 20?g mouse body weight; sonication frequency, 1.3?MHz; and sonication power, 2.06?W/cm2. 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. |
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Keywords: | Acoustic cavitation doxorubicin liposome HCC therapy liver tumor ultrasound-targeted microbubble destruction |
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