Dual-frequency ultrasound activation of nanomicellar doxorubicin in targeted tumor chemotherapy

Introduction This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice. Methods We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two ( T 2 ) and five ( T 5 ) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. Results The results of the combination of frequencies 28 kHz (0.04 W/cm 2 ) and 3 MHz (2.00 W/cm 2 ) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication ( P