Abstract: Osteosarcoma (OS) is a malignant tumor with a high rate of recurrence. Recently, biodegradable Mg-based implants have become a new therapeutic platform for bone-related diseases. However, poor biosafety and deficient intelligent tumor-killing ability of Mg-based implants are still the main challenges for the precise treatment of OS. Herein, based on the excellent catalytic and photothermal conversion properties of nanozyme ferric oxide (Fe₃O₄), a novel two-step hydrothermal method for in situ preparation of Fe₃O₄ nanosheets on the surface of plasma electrolytic oxidation (PEO)-treated Mg alloy using Mg-Fe layered double hydroxides (Mg-Fe LDH) as precursor was proposed. Compared with Mg alloy, there were no obvious corrosion cracks on the surface of Fe₃O₄ nanosheets-coated Mg alloy (Fe₃O₄-NS) immersed in 0.9 wt.% NaCl for 14 days, which demonstrated the corrosion resistance of Mg alloy was significantly enhanced. Cytocompatibility experiments and hemolysis assay confirmed the great biocompatibility of Fe₃O₄-NS, especially, hemolysis ratio was lower than 1%. Meanwhile, Fe₃O₄-NS presented excellent catalytic oxidation capacity in the presence of H₂O₂, and its temperature can significantly increase from 27 °C to approximately 56 °C under NIR irradiation. Therefore, intelligent responsive Fe₃O₄ nanosheets-engineered Mg-based implants demonstrated excellent antitumor properties in vivo and in vitro due to their photothermal and chemodynamic synergetic effects. This study provides a novel approach for the preparation of Fe₃O₄ coatings on the surface of Mg alloys and a new strategy for the treatment of OS.

Key words: Mg alloy, Fe₃O₄ nanosheets, Photothermal effect, Chemodynamic therapy, Antitumor