Ultrasound-activatable transition metal complexes to potentiate sonodynamic therapy

Sonodynamic therapy (SDT) is an emerging non-invasive treatment that utilises low-intensity focused ultrasound to activate sonosensitisers at disease sites, leading to the production of reactive oxygen species (ROS) for therapeutic effects. Leveraging ultrasound as the activation source, SDT offers remarkable advantages, including deep tissue penetration, high spatiotemporal precision and excellent biosafety. The efficacy of SDT largely depends on the performance of the ROS sonosensitisers, making the development of more effective agents crucial for improving clinical outcomes. Recently, there has been growing interest in transition metal complexes as sonosensitisers for SDT due to their remarkable properties such as high ROS generation efficiencies and excellent stability that have been well established in photodynamic therapy. In this review, we summarise recent advances in the development of transition metal complexes as ROS sonosensitisers for SDT in the treatment of cancer, microbial infections and cardiovascular diseases. We highlight key design strategies to enhance sonosensitiser performance and to integrate SDT with other therapeutic modalities to achieve synergistic effects. Furthermore, we discuss current challenges in the clinical translation of transition metal-based sonosensitisers for SDT and explore future prospects for advancing their applications in SDT to improve patient outcomes. © 2025 The Author(s). Published by the Royal Society of Chemistry.