Ultralow Dose Iron-Copper Bimetallic Single-Atom Nanozymes for Efficient Photothermal-Chemodynamic Antibacterial and Wound Healing

The combination of photothermal and chemodynamic therapy (PTT-CDT) using single-atom nanozymes (SAzymes) shows great promise in combating pathogenic and drug-resistant bacteria. However, the photothermal conversion efficiency and catalytic activity of SAzymes with solely metal sites remain inadequate, often requiring high doses for effectiveness. Herein, a bimetallic single-atomic nanozymes with Fe and Cu active sites (FeCu BSNs) designed is reported for efficient treatment of bacterial infections through hyperthermia-amplified nanozyme catalysis strategy. The FeCu BSNs demonstrate remarkable peroxidase (POD) activity with a specific activity (SA) of 752.25 U mg^-1, which is 2.3 folds larger than that of Fe SAzymes (323.45 U mg^-1). Additionally, their photothermal effect achieve a photothermal conversion efficiency up to 56.26%, which is two times higher that of Fe SAzymes (29.69%) and Cu SAzymes (25.55%). These enhancements can be attributed to the hybridization of Fe and Cu sites. The FeCu BSNs-mediated PTT-CDT combination therapy demonstrates potent antibacterial effects in both in vitro and in vivo models, attributed to high levels of reactive oxygen species (ROS) generation and hyperthermia. This study effectively validates the application of ultralow-dose bimetallic single-atom nanozymes in PTT-CDT for wound healing, offering a promising approach for enhanced wound recovery.