Towards an understanding of the mechanisms of therapeutic ultrasound on biomimetic models of cancer

Abstract

Therapeutic ultrasound is transforming the treatment of a range of malignancies in a non-invasive and non-systemic manner. Low-intensity ultrasound (LIUS) has been proposed to selectively eradicate cancer cells but the underlying biological mechanisms remains unknown. To gain an understanding of this phenomenon, 2D breast cancer monocultures were sonicated at varying acoustic intensities (0.1–0.5 W·cm−2) and excitation times (1–10 minutes). Additionally, 2D monocultures consisting of healthy cell lines were sonicated at varying acoustic intensities (0.1–0.5 W·cm−2) to determine any distinguishing biological responses. To begin recapitulating in vivo conditions, breast cancer cells were also seeded into 3D collagen hydrogels. At a 1 MHz frequency, 20% duty cycle, 100 Hz pulse repetition frequency, a significant drop in cancer cell viability is observed at a sonication intensity of 0.5 W·cm−2 and over 10 minute excitation time. Healthy counterparts subjected to the same parameters revealed no distinguishing effects. Sonication of breast cancer cells seeded in 3D collagen hydrogels revealed no effect in cell viability compared to non-sonicated controls. The acoustic wave propagation software OptimUS was used to determine the influence culturing plates have on ultrasound propagation, revealing these materials can significantly vary the acoustic field at frequencies relevant to LIUS.