Non-antibiotic nanoplatform based CuS/AuNCs@Lip NPs for inhibition pneumonia caused by MRSA and its mechanism exploration

<i>Methicillin-resistant Staphylococcus aureus</i> (MRSA) is a major threat to human health due to its multi-antibiotic resistance, either intrinsic or acquired. One of the acquired mechanisms lies in MRSA biofilms, which shield bacteria from antibiotic eradication, contributing to chronic infections. To address this challenge, we constructed the novel non-antibiotic nano-delivery platforms based on copper sulfide/gold nanocluster@liposomes nanoparticles (CuS/AuNCs@Lip NPs). Upon the excitation of 1064 nm near-infrared light, these NPs exhibit excellent photothermal effect and reactive oxygen species (ROS) generation ability, destroying the structure of bacterial membrane to kill MRSA and removing biofilm effectively. <i>In vivo</i> experiments demonstrated the target enrichment at infection sites, significant therapeutic efficacy in the subcutaneous cyst and pneumonia models caused by MRSA in mice, and a favorable biosafety profile. This study provides novel non-antibiotic strategies for treating drug-resistant bacterial infections that combine efficient antimicrobial properties with biosafety.