Synergizing Pt–O–Mo Coupling and Electron Gradient: A Nanozyme Paradigm for Low-Dose Tumor Radiosensitization

Nanozymes suffer from insufficient catalytic activity and sluggish electron transfer, while hypoxic tumor microenvironment (TME)-induced radioresistance and limited reactive oxygen species accumulation hinder radiotherapy efficacy. Existing nanozyme radiosensitizers often require high-dose radiotherapy or combined drugs to achieve only a modest efficacy. Herein, we report a Pt-anchored MoO x (MPP) nanozyme synthesized via a surface defect-ligand reduction strategy with Pt nanoclusters loading up to 34.39 ± 0.92 wt %. It features a gradient electron-transfer interface constructed by strong Pt–O–Mo interactions, which enables atomic-level integration of Pt 0 /Pt 2+ nanoclusters with MoO x and the simultaneous introduction of oxygen vacancies and an interfacial electron pool. Density functional theory calculations confirm the interface upshifts MoO x ’s d-band center, accelerates Mo → Pt electron transfer, and reduces the H 2 O 2 dissociation barrier to 0.18 eV. Consequently, MPP achieves a catalase-like specific activity of 3884.53 U mg –1 (2-fold natural catalase, 7528-fold MnO 2 ) and a turnover number (TON) of 25.7021 s –1 . Additionally, MPP exhibits a quantitative factor for electron transfer efficiency of 1.75, exceeding reported nanozymes. In the acidic TME, MPP orchestrates a catalase/superoxide dismutase/oxidase cascade to relieve hypoxia and generate • O 2 – / 1 O 2 . Synergized with Pt’s high- Z effect, MPP amplifies the efficacy of 6 Gy with low-dose radiotherapy, achieving 75.24% tumor inhibition rate without inducing systemic toxicity. This gradient electron-transfer interface strategy provides a promising paradigm for high-efficacy, low-toxicity tumor-specific therapy.