Comparison of the effects of ultrasound in a repetitive mode and acoustically active lipospheres in the presence of doxorubicin on breast adenocarcinoma

Purpose: We want to compare the synergistic effect of low-intensity, dual-frequency (dual) ultrasound (US), applied in a repetitive sonication mode, and acoustically active lipospheres (AALs) containing doxorubicin (DOX) in a murine model (Balb/C). Subjects and Methods: The tumor-bearing mice were divided into nine groups, namely two untreated groups (control and sham), and seven experimental groups, including treated with dual-frequency US (150 kHzcontinuous + 1MHzpulse), triple exposure (3x30min) dual-frequency US, DOX (2 mg/kg intravenous), DOX in combination with single exposure (30 min) to dual-frequency US (drug + dual), DOX in combination with triple (3 x 30 min) exposure to dual-frequency US (drug + dual [REP]), AALs containing the drug-loaded (AAL), and a group receiving AAL in combination with single exposure (30 min) dual-frequency US (AAL + dual), respectively. Results: The effectiveness of DOX on tumor growth was enhanced by a factor of three when combined with the triple exposures of dual US (drug + dual [REP]). This combination protocol further increased the times needed for each tumor to 2 and 7 times its initial volume, respectively by 94% and 36% compared to the drug group. During the 30 days, following the treatment of tumors, the relative volume of tumors in AAL group was 118% less than that of the drug group. The survival rate of the groups treated with drug and AAL + dual was increased by 78.7% and 167% compared with sham, respectively. Conclusion: Although as a short treatment, a major improvement in treatment was observed by (drug + dual [REP]) compared with other treatments, the AAL + dual treatment compared with (drug + dual [REP]) showed an increase in the survival rates, hence more preferable over long periods.