Photothermal‐Activable Artificial Macrophage With Amplified Systemic Antibacterial Responses to Combat Primary and Secondary Infection

Abstract

ABSTRACT The rapid evolution of antibiotic‐resistant bacteria, particularly methicillin‐resistant Staphylococcus aureus ( MRSA ), poses a critical threat to human healthcare, underscoring the need for antibiotic‐free antibacterial strategies that achieve both effective pathogen eradication and sustained protection against reinfection. Here, inspired by the functions of natural macrophages, we report the de novo design of an Ir/TiN‐based photothermal‐activable artificial macrophage (ITN Art‐M) with enhanced systemic antibacterial activity to combat primary and secondary infections caused by antibiotic‐resistant bacteria. The experimental studies and theoretical calculations reveal that the ITN Art‐M displays spiky topology, robust photothermal properties, and electron‐rich Ir‐Ti catalytic sites for reactive oxygen species (ROS) production, which can efficiently capture and kill antibiotic‐resistant bacteria. Meanwhile, the synthesized ITN Art‐M can induce severe bacterial antigen leakage and exposure through synergistic oxidative and hyperthermic stress, thereby potently stimulating systemic antibacterial responses, assisting in the elimination of primary infections and establishing durable defensive surveillance against secondary infections. Notably, ITN Art‐M demonstrates superior MRSA eradication and recurrence prevention, offering a potent, intelligent alternative that may surpass conventional antibiotics in combating bacteria and many other pathogenic cells.