Synergistic Chemodynamic–Photothermal Antibacterial Activity of a Nanozyme Derived From Processed Pyritum

ABSTRACT Pyritum can eliminate blood stasis and promote the healing of muscles and bones, which has been used as a traditional mineral medicine in China for thousands of years. However, the mechanisms of action and processing methods of Pyritum were not illustrated. This study developed a natural nanozyme with synergistic antibacterial effects by integrating chemodynamic therapy (CDT) and photothermal therapy (PTT) with the mineral medication Pyritum . Thermodynamic software HSC Chemistry and FactSage 8.2 were employed to clarify the phase transition mechanism during the traditional processing of Pyritum by calcination and vinegar quenching. The ideal processing conditions were identified by theoretical and experimental optimization: calcination at 800°C for 60 min, followed by quenching with vinegar at a mass ratio of 3:1 ( Pyritum to vinegar), resulting in traditionally processed Pyritum (TPP). The main crystalline phase of TPP was Fe 7 S 8 . Using wet ball milling, TPP nanoparticles (TPP‐NPs) were successfully prepared with a median particle size ( D 50 ) of 0.43 μm. TPP‐NPs exhibited a high photothermal conversion efficiency of 72.69% and significant peroxidase‐like (POD‐like) activity, characterized by a Michaelis constant ( K M ) for H 2 O 2 of 6.21 mM and a catalytic rate constant ( k cat ) of 0.73 s −1 . TPP‐NPs could synergistically inhibit the proliferation of Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) (with an antibacterial rate > 99%) by promoting hydroxyl radical (·OH) generation via the combined CDT‐PTT action. This work not only provides a theoretical foundation for the TPP but also opens a new pathway for preparing high‐performance nanozymes from natural minerals, demonstrating significant potential in combating drug‐resistant bacterial infections.