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Quorum sensing (QS), a bacterial communication system regulating virulence and biofilm formation, presents a target for novel therapies. Cuproptosis death is a innovation mode of death, however, this effect may be partially inhibited by glutathione (GSH). Buthionine sulfoximine (BSO) is responsible for GSH biosynthesis and has been identified as a potential promoter of cuproptosis death. Here, Cu<jats:sub>2<\/jats:sub>O\u2010BSO NPs with lung adhesion and mucus penetration ability are synthesized by incorporating BSO onto Cu<jats:sub>2<\/jats:sub>O, and modifying it with DOPA and PEG. Cu<jats:sub>2<\/jats:sub>O\u2010BSO NPs demonstrated a broad\u2010spectrum antibacterial activity against both Gram\u2010positive and Gram\u2010negative bacteria, making it a viable treatment option for MRSA\u2010induced acute pneumonia. Specifically, Cu<jats:sub>2<\/jats:sub>O\u2010BSO NPs can synergistically enhance bacterial cuproptosis\u2010like death, hinder the QS system, eradicate biofilms, reduce the virulence of strains, stimulate the chemotaxis and phagocytosis of macrophages, and ultimately improve in mice with severe pneumonia. This research demonstrated the potential of Cu<jats:sub>2<\/jats:sub>O\u2010BSO NPs for a wide\u2010ranging antibacterial alternative, providing promise for addressing microbial resistance and combatting biofilm formation. Additionally, it established a target and theoretical foundation for the clinical treatment of numerous challenging cases of acute drug\u2010resistant bacteria.<\/jats:p>","DOI":"10.1002\/advs.202408580","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T04:12:41Z","timestamp":1740197561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Mucous Permeable Nanoparticle for Inducing Cuproptosis\u2010Like Death In Broad\u2010Spectrum Bacteria for Nebulized Treatment of Acute Pneumonia"],"prefix":"10.1002","volume":"12","author":[{"given":"Huiqun","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyuan","family":"Hua","sequence":"additional","affiliation":[{"name":"Zhejiang 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