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M1\u2010polarized AMs generate substantial ROS and potent pro\u2010inflammatory cytokines, triggering a widespread secondary inflammatory cascade. Therefore, ARDS is trapped in a vicious \u201cROS\u2014M1 macrophages polarization\u2014inflammation\u2014ROS\u201d cycle, which markedly exacerbates disease progression. Constrained by this, previous monotargeted therapeutic approaches exhibited suboptimal efficacy and failed to meet clinical needs. Herein, a vicious cycle\u2010normalizing strategy was introduced to target the dual pathogenic mediators in the ARDS microenvironment. Specifically, phosphatidylserine\u2010modified and metformin\u2010loaded biomimetic honeycomb manganese dioxide nanoparticles (PS\u2010HM\/M NPs) were developed, with superoxide dismutase (SOD) and catalase (CAT)\u2010mimetic properties to eliminate excessive intracellular ROS while metformin efficiently promotes phenotypic transition of AMs toward the pro\u2010resolution M2 state. In an acute lung injury (ALI) model, PS\u2010HM\/M NPs successfully interrupted the malignant cycle and significantly resolved inflammation. In conclusion, this work highlighted the critical role of regulating the ROS\u2010macrophage crosstalk and provided a promising avenue for ARDS therapy.<\/jats:p>","DOI":"10.1002\/adhm.71369","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:46:53Z","timestamp":1782211613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pro\u2010Inflammatory Vicious Cycle\u2010Normalizing Biomimetic Nanoparticles to Treat Acute Respiratory Distress Syndrome"],"prefix":"10.1002","volume":"15","author":[{"given":"Si\u2010Si","family":"Yu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Qing","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 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