A Homing Missile‐Like Nanotherapeutic with Single‐Atom Catalytic Sites for In Situ Elimination of Intracellular Bacterial Pathogens

Abstract Intracellular bacterial pathogens hiding in host cells tolerate the innate immune system and high‐dose antibiotics, resulting in recurrent infections that are difficult to treat. Herein, a homing missile‐like nanotherapeutic (FeSAs@Sa.M) composed of a single‐atom iron nanozyme (FeSAs) core coated with infected macrophage membrane (Sa.M) is developed for in situ elimination of intracellular methicillin‐resistant S. aureus (MRSA). Mechanically, the FeSAs@Sa.M initially binds to the extracellular MRSA via the bacterial recognition ability of the Sa.M component. Subsequently, the FeSAs@Sa.M can be transported to the intracellular MRSA‐located regions in the host cell like a homing missile under the guidance of the extracellular MRSA to which it is attached, generating highly toxic reactive oxygen species (ROS) for intracellular MRSA killing via the enzymatic activities of the FeSAs core. The FeSAs@Sa.M is far superior to FeSAs in killing intracellular MRSA, proposing a feasible strategy for treating intracellular infections by in situ generating ROS in bacterial residing regions.