Small molecule sonosensitizers in cancer therapy: recent advances and clinical prospects

Sonodynamic therapy (SDT) has emerged as a promising cancer treatment modality, offering deep-tissue targeting while minimizing damage to surrounding healthy tissues. Building upon the pioneering work of Kremkau and Umemura in SDT, researchers worldwide have expanded and diversified sonosensitizers. From their early foundations, small molecule sonosensitizers have now evolved to include porphyrins, phthalocyanines, BODIPY dyes, cyanines, xanthene dyes, phenothiazines, metal complexes, and other organic molecules. By combining deep tissue penetration of ultrasound (US) with synergistic reactive oxygen species (ROS) generation, SDT overcomes the depth limitations of photodynamic therapy (PDT), significantly enhancing its potential for tumor treatment. In this review, we systematically examine recent advances in small molecule sonosensitizers, focusing on their design strategies and corresponding performance. Furthermore, we highlight their clinical anti-tumor applications and current limitations, providing valuable insights for the future rational design of sonosensitizers.