Sonodynamic therapy (SDT) has emerged as a promising option for the minimally invasive treatment of solid cancerous tumours. SDT requires the combination of three distinct components: a sensitising drug, ultrasound, and molecular oxygen. Individually, these components are non-toxic but when combined together generate cytotoxic reactive oxygen species (ROS). The major advantage of SDT over its close relative photodynamic therapy (PDT), is the increased penetration of ultrasound through mammalian tissue compared to light. As a result, SDT can be used to treat a wider array of deeper and less accessible tumours than PDT. In this article, we critically review the current literature on SDT and discuss strategies that have been developed in combination with SDT to enhance the therapeutic outcome.

Sonodynamic therapy (SDT) represents an emerging approach that offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. It involves the sensitization of target tissues with a non-toxic sensitizing chemical agent and subsequent exposure of the sensitized tissues to relatively low-intensity ultrasound. Essentially, both aspects (the sensitization and ultrasound exposure) are harmless, and cytotoxic events occur when both are combined. Due to the significant depth that ultrasound penetrates tissue, the approach provides an advantage over similar alternative approaches, such as photodynamic therapy (PDT), in which less penetrating light is employed to provide the cytotoxic effect in sensitized tissues. This suggests that sonodynamic therapy may find wider clinical application, particularly for the non-invasive treatment of less accessible lesions. Early SDT-based approaches employed many of the sensitizers used in PDT, although the manner in which ultrasound activates the sensitizer differs from activation events in PDT. Here we will review the currently accepted mechanisms by which ultrasound activates sensitizers to elicit cytotoxic effects. In addition, we will explore the breath of evidence from in-vitro and in-vivo SDT-based studies, providing the reader with an insight into the therapeutic potential offered by SDT in the treatment of cancer.

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