Semiconducting Titanate Supported Ruthenium Clusterzymes for Ultrasound‐Amplified Biocatalytic Tumor Nanotherapies

Abstract The external‐stimulation‐induced reactive‐oxygen‐species (ROS) generation has attracted increasing attention in therapeutics for malignant tumors. However, engineering a nanoplatform that integrates with efficient biocatalytic ROS generation, ultrasound‐amplified ROS production, and simultaneous relief of tumor hypoxia is still a great challenge. Here, we create new semiconducting titanate‐supported Ru clusterzymes (RuNC/BTO) for ultrasound‐amplified biocatalytic tumor nanotherapies. The morphology and chemical/electronic structure analysis prove that the biocatalyst consists of Ru nanoclusters that are tightly stabilized by Ru‐O coordination on BaTiO3. The peroxidase (POD)‐ and halogenperoxidase‐like biocatalysis reveals that the RuNC/BTO can produce abundant •O2− radicals. Notably, the RuNC/BTO exhibits the highest turnover number (63.29 × 10−3 s−1) among the state‐of‐the‐art POD‐mimics. Moreover, the catalase‐like activity of the RuNC/BTO facilitates the decomposition of H2O2 to produce O2 for relieving the hypoxia of the tumor and amplifying the ROS level via ultrasound irradiation. Finally, the systematic cellular and animal experiments have validated that the multi‐modal strategy presents superior tumor cell‐killing effects and suppression abilities. We believe that this work will offer an effective clusterzyme that can adapt to the tumor microenvironment‐specific catalytic therapy and also provide a new pathway for engineering high‐performance ROS production materials across broad therapeutics and biomedical fields.