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Adv."],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:p>Acute pneumonia triggered by pathogen infection and lung injury persists as a critical global life-threatening issue. Cluster of differentiation 24 (CD24), by selectively inhibiting the inflammatory response associated with damage-associated molecular patterns (DAMPs) through the interaction with Siglec, has appeared as a unique paradigm to alleviate acute pneumonia, yet its effective pulmonary delivery remains challenging. Here, we report on reactive oxygen species (ROS)\u2013responsive and mucus-penetrable nanogels (ROS\u03bcNG) for pulmonary CD24 delivery to rescue acute pneumonia by selective inhibition of hyperinflammatory response. CD24-loaded nanogels (CD24-ROS\u03bcNG) exhibit excellent stability during nebulization, efficient mucus penetration, and inflammation-triggered CD24 release, affording over 80% drug enrichment in lung tissues through nebulization inhalation. In lipopolysaccharide-induced severe acute pneumonia mouse models, nebulized CD24-ROS\u03bcNG effectively attenuates cytokine storm, suppresses DAMP-mediated inflammation, and mitigates lung injury, achieving an over 3.5-fold increase in survival rate compared to intravenous administration of over 12-fold higher dose of free CD24. In an H1N1 virus influenza model, CD24-ROS\u03bcNG not only prevents cytokine storm but also preserves neutrophil-mediated viral clearance by limiting excessive neutrophil extracellular trap formation, thereby avoiding uncontrolled inflammation while maintaining antiviral defenses. These inhalable CD24 nanogels establish a strategy to manage pulmonary hyperinflammatory disorders.<\/jats:p>","DOI":"10.1126\/sciadv.aec3712","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:59:26Z","timestamp":1787162366000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["ROS-responsive nanogels enable inhaled CD24 immunotherapy for selective hyperinflammation suppression in severe pneumonia"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0336-9094","authenticated-orcid":true,"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Materials, College of Chemistry, Chemical Engineering, and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, 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