Nanoparticle‐Like Scavenger Mediated by NIR/pH Stimulation for MRSA‐Associated Infections

Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a severe global clinical threat due to its multi-antibiotic resistance, abundant virulence factors, and complex pathogenic mechanisms. In the present study, hollow copper sulfide (CuS) nanoparticles (NPs) with a strong photothermal effect were employed as carriers for the loading of the NO-releasing bioactive molecule S-nitrosoglycine (GSNO). These NPs were also camouflaged with mouse red blood cell membranes (RBCMs) via extrusion to fabricate CuS-GSNO@RBCM NPs designed to effectively eliminate MRSA and its biofilms. Under 1064 nm near-infrared laser irradiation, CuS NPs had a mild photothermal effect, establishing an in situ catalytic platform that boosted reactive oxygen species (ROS) production. In the acidic infectious microenvironment, the release of copper ions induced GSNO to produce NO for reactive nitrogen species (RNS) generation. The ROS and RNS generated in situ by this system consumed endogenous MRSA glutathione, disrupting redox homeostasis, with the additional presence of copper ion-mediated copper death forming a multi-bactericidal network. The RBCMs also neutralized proteins secreted by MRSA to reduce lung cell injury. In vitro and in vivo experiments were employed to verify the MRSA-elimination efficacy of the proposed system, which offers an innovative nanotherapeutic strategy for the precise treatment of drug-resistant bacterial infections.