Anticancer Potency of Cytotoxic Drugs after Exposure to High-Intensity Focused Ultrasound in the Presence of Microbubbles and Hematoporphyrin

Abstract

Chemotherapy is undertaken perioperatively to improve the efficacy of high-intensity focused ultrasound (HIFU) for solid tumors. HIFU at a sufficient intensity for tissue ablation has recently been applied for drug delivery; ultrasonic cavitation plays an important part in HIFU and drug delivery. Hematoporphyrin and microbubbles are adjuncts because they aid cavitation. The effect of HIFU (1.0 MHz; 12,999 W/cm(2) in continuous waves), in the presence of hematoporphyrin and/or microbubbles, on the anticancer potency of 5-fluorouracil, cisplatin, paclitaxel, mitomycin C or adriamycin, was investigated. Insonated adriamycin resulted in a lower death rate of human cancer cells HO-8910 (45.85 ± 2.65% vs 34.84 ± 1.21%, p < 0.05), which was exacerbated when employing hematoporphyrin (34.84 ± 1.21% vs 23.09 ± 7.82%, p < 0.05) or hematoporphyrin combined with microbubbles (34.84 ± 1.21% vs. 8.79 ± 3.69%, p < 0.05); the therapeutic activity was not affected when adding microbubbles alone. High-performance liquid chromatography detected a smaller peak area after subjecting adriamycin to HIFU with the use of hematoporphyrin alone or combined with microbubbles. The other drugs were not affected. Hematoporphyrin, microbubbles and adriamycin increased the throughput of hydroxyl radicals resulting from cavitation as determined by iodine and methylene blue assays. These data suggested that the anticancer activity of a drug may be decreased by HIFU exposure (particularly in the presence of hematoporphyrin and microbubbles). Cavitation produced reactive species that attacked drug molecules, thereby decreasing their antitumor potency; this process was enhanced if the drug itself generated free radicals under insonation.