This study aimed to evaluate the effect of dual-frequency sonication in the presence of thalidomide angiogenesis inhibitor and nanomicelles containing doxorubicin on inhibiting the growth and angiogenesis of breast adenocarcinoma in BALB/c female mice. Sixty mice carrying the tumor were divided into 12 groups: (A) control, (B) 28 kHz and 3 MHz sonication, (C) thalidomide, (D) thalidomide and 28 kHz, (E) thalidomide and 3 MHz, (F) thalidomide and dual-frequency sonication, (G) doxorubicin, (H)

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... nomicelles containing doxorubicin, (I) nanomicelles containing doxorubicin and dual-frequency sonication, (J) thalidomide and doxorubicin, (K) thalidomide and nanomicelles containing doxorubicin, and (L) thalidomide and nanomicelles containing doxorubicin and dual-frequency sonication. The delay in the tumor growth and angiogenesis percent were extracted. Pathological and immunohistochemical studies were performed to confirm the treatment. The findings of tumor growth retardation parameters and animal survival were significantly different in group L from all groups (P < 0.05). The highest rate of inhibition was in group L with a 46% inhibition. In group L, 100% of the animals survived until day 49. In groups F, C, G, B, and A, all the animals survived 45, 42, 39, 32, and 30 days, respectively. Pathological results showed a decrease in tumor grade in groups K and L. Histopathological results demonstrate a decrease in group L angiogenesis compared to group C. These findings were consistent with the results of color Doppler ultrasound imaging. Dual-frequency sonication in the presence of thalidomide and doxorubicin-containing nanomicelles inhibits tumor growth and angiogenesis.