CuFeS2 nanozyme regulating ROS/GSH redox induces ferroptosis-like death in bacteria for robust anti-infection therapy
Huidong Wang, Jiadong Guo, Yangzi Yang, Ning Wang, Xiao Yang, Liang Deng, Xiankun Cao, Zhaoyang Ran, Dong Fang, Kang Xu, Yingchun Zhu, Jie Zhao, Jingke Fu, Yongqiang Hao
Abstract
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.