Sonodynamic therapy

Initially developed for diagnostic imaging, ultrasound is increasingly being considered for non-invasive therapeutic modalities. The use of high-intensity focused ultrasound (HIFU) is now a routine clinical practice for treating localized cancers (notably prostate and liver cancers) and uterine fibroids by hyperthermal effect. Focused ultrasound is also used to mechanically fractionate tissue or kidney and gallstones (histotripsy and lithotripsy), to destroy opaque crystalline lenses (cataracts) or to treat glaucoma by cyclo coagulation.

New clinical indications for HIFU are currently being developed, notably to treat patients with calcified aortic stenosis using a non-invasive method (Cardiawave technology currently undergoing clinical validation), or to deliver drugs targeting the central nervous system by transient opening of the blood-brain barrier.

However, an emerging field in preclinical – low-frequency sonotherapy – is based on the use of low-intensity ultrasound coupled with sonosensitizers to induce numerous cell-stress-inducing effects. These effects may be physical, such as mechanical shearing of the cell membrane or moderate hyperthermal effects. They can also be chemical, via cytotoxic effects induced by activated oxygen species produced by water pyrolysis, or sonoluminescence triggered by ultrasound and activated by sonosensitizers.

This article explains the physical principles of sonotherapy, as well as the parameters to be mastered to induce the ultrasonic effect relevant to activating cellular stress mechanisms. It also describes the different classes of organic or inorganic sonosensitizers used in the literature, and the medical applications envisaged. Although the clinical benefits of sonotherapy have yet to be fully demonstrated, we describe here the preclinical potential of sonotherapy and therapies combining it with other therapeutic modalities (chemotherapy, photodynamic therapy, radiotherapy, gene therapy and immunotherapy).