Semiconducting Titanate Supported Ruthenium Clusterzymes for Ultrasound-Amplified Biocatalytic Tumor Nanotherapies.

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 BaTiO 3 . The peroxidase (POD)- and halogenperoxidase-like biocatalysis reveals that the RuNC/BTO can produce abundant •O 2 - 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 H 2 O 2 to produce O 2 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.