Current roles of metals in arming sonodynamic cancer therapy

Emerging sonodynamic therapy strategies shed light on conquering oxygen dependence and penetration restriction in photodynamic therapy for non-invasive tumor treatments. During the flourishing of novel sonosensitizer construction strategies, the introduction of metals broadens the fabrication modalities of sonosensitizer and perfects the presently insufficient therapeutic effects of single-modality sonodynamic therapy. In this review, cutting-edge metal-based sonosensitizers are categorized according to the utilized metals to demonstrate the unique role of different metals in facilitating sensitizer construction, optimizing sonodynamic performance, introducing synergistic treatments, and reshaping tumor microenvironment. The thread throughout the text is the specific mechanisms activated by the introduction of metals and their versatile functionalities in boosting sonodynamic therapy. Furthermore, state-of-the-art approaches to initiate systemic anticancer immunity by metal-based sonosensitizers are highlighted to inspire the versatile application of metal-mediated sonodynamic effects. Finally, the challenges and perspectives are revealed, aiming to provide insights into using metals in sonodynamic therapy and incorporating sonodynamic therapy into multi-modal anticancer treatments.