Bacteria-mimetic nanomedicine for targeted eradication of intracellular MRSA.

Drug-resistant infections caused by intracellular bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), which are often hidden inside macrophages, pose a significant threat to human health. Various nanomedicines have been developed to combat intracellular MRSA; however, their poor uptake and fast clearance from macrophages often result in insufficient enrichment of antibacterial agents intracellularly, leading to low antibacterial efficacy. Here, we developed bacterial membrane-coated mesoporous SiO2 nanoparticles (MSN) loaded with vancomycin (Van), a classic antibiotic. These nanoparticles can be specifically recognized and internalized by macrophages and self-aggregated into micron-sized MSN clusters based on cucurbit[7]uril-adamantane host-guest interactions, allowing for slow clearance and extended retention in infected macrophages. The acid-triggered, sustainable release of Van from MSN aggregates effectively killed MRSA in infected macrophages and significantly alleviated inflammation caused by intracellular bacterial infections both in vitro and in vivo. This work not only provides a practical solution to effectively treat drug-resistant intracellular infections but also offers new insights for the design and development of antibacterial nanomaterials.