A Sonosensitive Heterometallic Polyoxometalate for Highly Efficient Chemo‐Sonodynamic Synergistic Cancer Therapy

Chemo-sonodynamic synergistic therapy (CSDT) integrates the advantages of both chemodynamic therapy (CDT) and sonodynamic therapy (SDT), including specificity, non-invasiveness, high penetration, and controllability, and it is especially suitable for deep-seated tumors. However, there is still a lack of effective CSDT agents with long-term stability, excellent water solubility, biocompatibility, and highly efficient catalytic activities. To address these challenges, we report a rare sonosensitive polyoxometalate (POM), H₁₁[Er₂Sb₂W₇O₂₃(OH)(DMF)₂(SbW₉O₃₃)₂]·17H₂O (ErSbW), featuring an atomically precise capsule-like structure with good solubility, molecular stability, and biosafety under physiological conditions. In vitro studies reveal ErSbW's remarkable CDT efficiency in catalyzing the generation of reactive oxygen species (ROS). More importantly, the efficiency can be further distinctly augmented by three times with the presence of ultrasound irradiation, suggesting a pronounced synergistic enhancement effect in ErSbW. Most notably, ErSbW-mediated CSDT achieved complete eradication of deep-seated tumors in a melanoma model at the dose of 35 µg kg^-1. This work not only provides a unique POM-based molecular agent for CSDT but also demonstrates the great potential of POM materials in synergistic cancer therapies.