Nanomaterial-Induced Bacterial Ferroptosis-Like Death: A Novel Strategy to Counteract Antimicrobial Resistance

Xiaoyue Wu,1– 3,* Yanying Wang,1,* Tinglin Zhang,2,4 Zhaoshen Li,1,2,4,5 Yiqi Du,1,2,4,5 Jie Gao1,2,4,5 1Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3The 925th Hospital of PLA Joint Logistics Support Force CN, Guiyang, 550000, People’s Republic of China; 4Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, 200433, People’s Republic of China; 5National Key Laboratory of Immunology and Inflammation, Naval Medical University, Shanghai, 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-21-31166666, Email gaojiehighclea@smmu.edu.cn Yiqi Du, Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-021-31161344, Email duyiqi@hotmail.comAbstract: The escalating crisis of antimicrobial resistance (AMR) poses a profound threat to global public health, necessitating the development of alternative antibacterial strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising strategy for combating drug-resistant bacteria. In this review, we systematically summarize how nanomaterials precisely regulate bacterial iron metabolism through chemical kinetics, photodynamics, sonodynamics, and nanoenzyme catalytic pathways, which promote iron storage and reactive oxygen species (ROS) generation, destroy the antioxidant defense system, and eventually lead to ferroptosis-like lipid peroxidation and membrane damage. In addition, this study focused on the synergistic activation of the host immune response by nanomaterials through the regulation of macrophage polarization and the cytokine network, thereby enhancing bacterial clearance and tissue repair. As an emerging nonantibiotic antimicrobial method, nanomaterial-mediated bacterial ferroptosis provides new insights and approaches to address the challenge of drug-resistant infections.Keywords: ferroptosis-like death, nanomaterials, antibacterial strategy, drug resistance, chemotherapeutic therapy, immune regulation, synergistic therapy