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The complex and heterogeneous pathophysiology of TBI and cerebral ischemia\u2010reperfusion injury (CIRI), in addition to the blood\u2010brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)\u2010responsive neutrophil\u2010targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.<\/jats:p>","DOI":"10.1002\/advs.202308719","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T15:13:36Z","timestamp":1711206816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics"],"prefix":"10.1002","volume":"11","author":[{"given":"Qingchun","family":"Mu","sequence":"first","affiliation":[{"name":"Gaozhou People's Hospital  Maoming 525200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery First Affiliated Hospital of Harbin Medical University  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madiha 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Pharmaceutical Sciences Guangdong Provincial Key Laboratory of New Drug Screening Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Basic Medical College Guilin Medical University  Guilin 541199 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huamiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Center for Regeneration and Aging Medicine the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu 322000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Center for Regeneration and Aging Medicine the Fourth Affiliated Hospital of School of Medicine, and International School of 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