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This study reports a baicalin\u2010based metal\u2010coordination nanomedicine with disulfiram (DSF) co\u2010loading to address one\u2010lung ventilation\u2010induced lung injury and reperfusion injury (OLV\u2010LIRI). Baicalin, known for its robust antioxidant properties, suffers from poor water solubility and stability. Leveraging nanotechnology, baicalin's coordination is systematically explored with seven common metal ions, designing iron\/copper\u2010mediated binary coordination nanoparticles to overcome these limitations. The self\u2010assembled nanoparticles, primarily formed through metal coordination and \u03c0\u2013\u03c0 stacking forces, encapsulated DSF, ensuring high colloidal stability in diverse physiological matrices. Upon a single\u2010dose administration via endotracheal intubation, the nanoparticles efficiently accumulate in lung tissues and swiftly penetrate the pulmonary mucosa. Intracellularly, baicalin exhibits free radical scavenging activity to suppress inflammation. Concurrently, the release of Cu<jats:sup>2+<\/jats:sup> and DSF enables the in situ generation of CuET, a potent inhibitor of cell pyroptosis. Harnessing these multifaceted mechanisms, the nanoparticles alleviate lung injury symptoms without notable toxic side effects, suggesting a promising preventive strategy for OLV\u2010LIRI.<\/jats:p>","DOI":"10.1002\/smll.202401056","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T11:21:08Z","timestamp":1723116068000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Coordination\u2010Driven Nanomedicine Mitigates One\u2010Lung Ventilation\u2010Induced Lung Injury via Radicals Scavenging and Cell Pyroptosis Inhibition"],"prefix":"10.1002","volume":"20","author":[{"given":"Yujie","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Affiliated Children's Hospital of Xiangya School of Medicine Central South University (Hunan Children's Hospital)  Changsha Hunan 410007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangqin","family":"Ou","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Children's Hospital of Xiangya School of Medicine Central South University (Hunan Children's Hospital)  Changsha Hunan 410007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziye","family":"Wei","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiLing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Children's Hospital of Xiangya School of Medicine Central South University (Hunan Children's Hospital)  Changsha Hunan 410007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Children's Hospital of Xiangya School of Medicine Central South University (Hunan Children's Hospital)  Changsha Hunan 410007 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Ma","sequence":"additional","affiliation":[{"name":"Hunan Prize Life Science Research Institute Co.  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