Valence-engineered catalysis-selectivity regulation of molybdenum oxide nanozyme for acute kidney injury therapy and post-cure assessment

The optimization of the enzyme-like catalytic selectivity of nanozymes for specific reactive oxygen species (ROS)-related applications is significant, and meanwhile the real-time monitoring of ROS is really crucial for tracking the therapeutic process. Herein, we present a mild oxidation valence-engineering strategy to modulate the valence states of Mo in Pluronic F127-coated MoO 3-x nanozymes (denoted as MF-x, x: oxidation time) in a controlled manner aiming to improve their specificity of H 2 O 2 -associated catalytic reactions for specific therapy and monitoring of ROS-related diseases. Experimentally, MF-0 (Mo average valence 4.64) and MF-10 (Mo average valence 5.68) exhibit exclusively optimal catalase (CAT)- or peroxidase (POD)-like activity, respectively. Density functional theory (DFT) calculations verify the most favorable reaction path for both MF-0- and MF-10-catalyzed reaction processes based on free energy diagram and electronic structure analysis, disclosing the mechanism of the H 2 O 2 activation pathway on the Mo-based nanozymes. Furthermore, MF-0 poses a strong potential in acute kidney injury (AKI) treatment, achieving excellent therapeutic outcomes in vitro and in vivo. Notably, the ROS-responsive photoacoustic imaging (PAI) signal of MF-0 during treatment guarantees real-time monitoring of the therapeutic effect and post-cure assessment in vivo, providing a highly desirable non-invasive diagnostic approach for ROS-related diseases. Nanozymes can mimic the activity of natural enzymes but are limited by poor reaction selectivity due to the lack of enzyme-like molecular recognition units as in natural enzymes. Here, the authors present a mild oxidation valence-engineering strategy to modulate the valence states of Mo in Pluronic F127-coated MoO 3-x nanozymes and show they can exhibit exclusive catalase- or peroxidase-like activities.