Sono‐Activated Artificial Vanadium Enzyme System for Efficient and Renewable Reactive Oxygen Nanobiocatalytic Therapies

ABSTRACT Biocatalytic generation of reactive oxygen species (ROS) by artificial enzymes offers a promising strategy for treating diverse diseases, including pathogenic infections and malignancies. However, the sluggish ROS biocatalytic efficiency and unstable active sites have hindered their potential clinical translation. Here, inspired by natural vanadium haloperoxidases and NADPH oxidase‐based ROS‐catalytic systems, we report the de novo design of a sono‐activated artificial vanadium enzyme (V x+ ‐SonoAE) for efficient and renewable ROS nanobiocatalytic therapies. By mimicking the electron transport chains and active VO 4 centers in natural enzymes, our innovative bionic approach not only yields efficient, robust, and precise vanadium active sites on TiO 2 but also enables continuous regeneration of redox centers during ROS biocatalysis via efficient electron transfer from sono‐activated TiO 2 to the V x+ site. Consequently, the V x+ ‐SonoAE achieves remarkable ROS‐catalytic performance with a superior turnover number (TON = 54 × 10 −3 s −1 ) that far surpasses the reported state‐of‐the‐art metal oxides‐based nanobiocatalysts. Moreover, this new artificial enzyme system demonstrates exceptional therapeutic efficiency in infection control and tumor regression with sustained and sono‐activated treatment properties. This work establishes a new paradigm for designing efficient and renewable nanobiocatalysts, combining fundamental insights from natural enzymatic systems with advanced materials engineering to create robust therapeutic platforms with long‐term efficacy.