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To address this challenge, this work engineers PBP2a antibody\u2010presenting membrane nanovesicles (AMVs) specifically designed to target the penicillin\u2010binding protein variant on the surface of methicillin\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA). Concurrently, this work develops pure ciprofloxacin nanoparticles (NanoCip) that, for the first time, exhibits exceptional self\u2010generated sonodynamic properties, attributed to hydrogen\u2010bond\u2010driven self\u2010assembly, while maintaining their inherent pharmacological efficacy. These NanoCip particles are integrated with AMVs to create a novel biomimetic nanomedicine, AMV@NanoCip. This formulation demonstrated remarkable MRSA\u2010targeting affinity in both in vitro and in vivo models, significantly enhancing antibacterial activity. Upon ultrasound stimulation, AMV@NanoCip achieves over 99.99% sterilization of MRSA in vitro, with a reduction exceeding 5.14 Log CFU. Prokaryotic transcriptomic analysis further elucidates the synergistic mechanisms by which AMV@NanoCip, coupled with ultrasound, disrupts the MRSA exoskeleton. In a MRSA\u2010induced pneumonia animal model, AMV@NanoCip+US results in a substantial bacterial load reduction in the lungs (99.99%, 4.02 Log CFU). This sequential treatment strategy (adhesion\u2010membrane disruption\u2010synergistic therapy) offers significant promise as an innovative therapeutic approach for combating bacterial infections.\n                  <\/jats:p>","DOI":"10.1002\/adma.202403612","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T07:31:12Z","timestamp":1727681472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Sono\u2010Triggered Biomimetically Nanoantibiotics Mediate Precise Sequential Therapy of MRSA\u2010Induced Lung Infection"],"prefix":"10.1002","volume":"36","author":[{"given":"Linyu","family":"Ding","sequence":"first","affiliation":[{"name":"State Key Laboratory of Infectious Disease Vaccine Development, Xiang'an Biomedicine Laboratory, National Innovation Platform for Industry\u2010Education Integration in Vaccine Research, Center for Molecular Imaging and Translational Medicine, School of Public Health Xiamen University  Xiamen 361102 P. 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