CuFeS2 nanozyme regulating ROS/GSH redox induces ferroptosis-like death in bacteria for robust anti-infection therapy

With the clinical prevalence of drug-resistant pathogenic bacteria, developing non-antibiotic strategies to treat multi-drug-resistant bacterial infections is urgent yet challenging. Ferroptosis is a non-apoptotic form of regulated cell death that can overcome drug resistance. Emerging evidence shows the potential of triggering ferroptosis-like for anti-infection therapy, but the direct delivery of iron species is inefficient and may cause detrimental effects. Herein, CuFeS2 nanozyme is revealed as a ferroptosis-like initiator to eradicate bacterial infections for effective anti-infection therapy. Upon activating by visible light irradiation or hydrogen peroxide, the as-prepared CuFeS2 nanozyme can significantly expedite reactive oxygen species generation, deplete intracellular glutathione, and interfere with respiratory metabolisms, resulting in lipid peroxidation-driven ferroptotic damage. Additionally, the CuFeS2 displays good photothermal conversion capacity under near-infrared light irradiation, further augmenting the antibacterial efficiency. Accordingly, the CuFeS2 nanozyme shows potent antibacterial activity against Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro. Moreover, it shows excellent biocompatibility and robust anti-infection effects in MRSA-infected wounds in vivo. This ferroptosis-like antibacterial strategy may open up new insights into the treatment of drug-resistant pathogen infection.