Acoustic Cluster Therapy displays theranostic capability in enhancing the effectiveness of liposomal doxorubicin treatment of human triple negative breast cancer in mice

Abstract

Acoustic Cluster Therapy (ACT) employs an intravenously-injected dispersion of clusters of microbubbles and oil microdroplets, in combination with ultrasound directed at the tumor, to enhance the delivery of a co-administered drug. Diagnostic ultrasound activates the clusters, causing the droplets to change phase and become large (> 20 m) bubbles which lodge in the tumor capillaries. Delivery-enhancement is then achieved using a low-frequency (e.g. 300 kHz) ultrasound field also directed at the tumor, which causes the stationary bubbles to pulsate whilst in direct contact with the vascular endothelium. ACT has been shown to significantly increase the efficacy of various chemotherapeutics in a variety of tumor models in mice. Here we demonstrate through preclinical in-vivo experiments that the efficacy of treating human triple negative breast cancer in mice with liposomal doxorubicin (Doxil®) is significantly enhanced by ACT; for example, 63 % of animals achieved complete, stable remission, in the group treated with the drug and ACT versus only 10 % for Doxil® alone (p < 0.02). We also show in the same experiments that the ACT contrast enhancement obtained under ultrasound activation of the ACT clusters, either before or during treatment, holds promise as an imaging biomarker for predicting response.