Abstract

Excessive accumulation of reactive oxygen species (ROS) impairs bone regeneration and angiogenesis in steroid-induced osteonecrosis of the femoral head (SONFH), yet current antioxidant therapies remain limited by low catalytic efficiency and short duration. Single-atom nanozymes (SANs), with their well-defined structures and maximal atomic efficiency, show great potential for treating ROS-induced diseases by mimicking natural enzymes. However, the strong binding between transition metal sites and electron-donating intermediates (e.g., O*, OH*, OOH*) creates high energy barriers, limiting their catalytic activities. Herein, single-atomic platinum is successfully embedded into CeO 2-x to form CeO 2-x /Pt SANI, which enhanced catalytic activity via an “island-sea” synergistic effect. Leveraging the unique charge-transfer structures and confinement effect of nanoislands, CeO 2-x /Pt SANI exhibits superior enzymatic activities than CeO 2 , attribute to the island-sea synergistic effect that facilitates strong electron transfer, as proved by density functional theory (DFT) calculations. DFT calculations further demonstrate that Pt incorporation increases oxygen vacancies and tunes the d-band center toward the Fermi level, facilitating ROS adsorption and accelerating redox reactions. Single-cell sequencing and experimental results confirm that CeO 2-x /Pt SANI reprograms the oxidative microenvironment, leading to significant therapeutic effects in SONFH. This study provides insights into the rational design of an advanced “island-sea” structured single-atom nanozyme to optimize the catalytic activity.