Advances and perspectives in organic sonosensitizers for sonodynamic therapy

Sonodynamic therapy (SDT), which involves a combination of low-intensity ultrasound (US) and a chemical sonosensitizer, has emerged as a promising minimally invasive and selective approach for the treatment of deep tumors. US not only increases cell membrane permeability, thereby enhancing the cellular uptake efficiency of chemical sonosensitizers, but also excites chemical sonosensitizers in deep tissues to generate reactive oxygen species (ROS), which in turn kill cancer cells. As compared with inorganic materials, organic sonosensitizers exhibit a defined chemical structure, controlled synthesis process, excellent biodegradability, and high ROS generation. However, they frequently exhibit poor water solubility, strong phototoxicity, and low tumor tissue targeting capacity. In this review, we address the currently accepted mechanisms in SDT and the recent progresses in organic sonosensitizers, discuss the strategies to improve the water solubility, tumor targeting capacity, biocompatibility, and therapeutic effects of organic sonosensitizers. The advantages of combining SDT with other cancer treatments, including phototherapy, chemodynamic therapy, chemotherapy, starvation therapy, gas therapy, and immune therapy are also demonstrated. Finally, the existing challenges and future perspectives on clinical SDT of tumor are discussed.