Ru-loaded snowflake-like digenite nanozymes for bacterial eradication through synergistic photothermal and catalytic therapy.

Antibiotic resistance poses an unavoidable challenge in clinical anti-infective therapy. Nanozymes offer a promising antibiotic-alternative strategy; however, insufficient ROS generation by nanozymes in the infection microenvironment severely limits their antibacterial efficacy. Herein, we designed a multifunctional snowflake-like artificial biocatalyst (Ru@SFD) featuring photothermally enhanced ROS-generating catalytic activity. This property works synergistically with photothermal therapy to combat methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm infections. Structural and spectroscopic analyses indicate that the Ru@SFD possesses a large number of RuS2 active sites on the surface. Enzyme-mimetic catalytic tests reveal that Ru@SFD exhibits outstanding intrinsic peroxidase (POD)-, horseradish peroxidase (HPO)- and catalase (CAT)-like activity as well as photothermal conversion capability. Meanwhile, the ROS-generating capacity of Ru@SFD can be further enhanced by the photothermal effect. In vitro and in vivo studies demonstrate that the synergistic combination of enzyme-mimetic catalysis and photothermal effects of Ru@SFD can effectively eradicate MRSA biofilms and rapidly sterilize wounds, with potency comparable to vancomycin but without associated inflammation or systemic toxicity. This study can provide robust guidance for creating effective antibiotic alternatives and lay a groundwork for the rational design of multimodal combined antimicrobial materials with enhanced therapeutic profiles.