Enhancing the efficacy of sonodynamic therapy through modulation of autophagy

Sonodynamic therapy (SDT), a noninvasive treatment modality that combines low intensity ultrasound with sonosensitizers, has shown significant potential in the treatment of cancer and metabolic diseases. However, SDT induced autophagy plays a dual role in disease progression, as it can promote either cell survival or cell death, and its effects are highly dependent on cell type and pathological context. This complexity underscores the urgent need for regulation of autophagy to optimize the therapeutic efficacy of SDT. Therefore, this review summarizes emerging regulatory strategies aimed at enhancing SDT efficacy through the induction or inhibition of autophagy. These encompass pharmacological approaches utilizing classic autophagy inhibitors/inducers, as well as nanomaterial-based strategies involving the design of nanocarriers or smart nano-sonosensitizers endowed with capabilities for targeted delivery and stimuli-responsive release. This review aims to provide a comprehensive theoretical framework for understanding the dual roles of autophagy in SDT and for achieving its precise and efficient regulation, thereby offering valuable insights for the development of more effective SDT based therapeutic strategies.