Sonodynamic therapy: Rapid progress and new opportunities for non-invasive tumor cell killing with sound

Cancer Lett. 2022 Apr 28:532:215592. doi: 10.1016/j.canlet.2022.215592. Epub 2022 Feb 11.


Solid tumor treatment relies heavily upon chemotherapies, radiation, surgical resection, and/or immunotherapies. Although many alternative non-invasive solid tumor therapies have been proposed through the years and continue to be tested in various contexts, tumor cell eradication remains a daunting task for the current cancer armamentarium. Indeed, solid tumors exhibit physically and biochemically heterogenous microenvironments, allowing them to easily acquire resistance mechanisms. Progress in sonodynamic therapy (SDT), a treatment modality capable of controlling tumor growth while limiting off-target effects and toxicities, has accelerated in recent years. SDT combines "sonosensitizing" agents with the non-invasive application of focused acoustic energy [i.e. focused ultrasound (FUS)] to drive highly localized formation of tumor cell-killing reactive oxygen species (ROS). Sonosensitizers selectively accumulate in tumor cells, after which FUS radiation eliminates the tumor by forcing the tumor cells to undergo cell death. In this article, we comprehensively review recent studies wherein SDT has been applied to treat primary and metastatic tumors. We discuss sonosensitizers, combination therapies with SDT, developments in defining the mechanism of SDT-induced cell cytotoxicity, and the promise SDT offers as a modulator of anti-tumor immunity.

Keywords: Focused ultrasound; Immunogenic cell death; Immunotherapy; Photodynamic therapy; Sonosensitizers.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Death
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Humans
  • Neoplasms* / drug therapy
  • Reactive Oxygen Species / metabolism
  • Tumor Microenvironment
  • Ultrasonic Therapy*


  • Reactive Oxygen Species