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Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood\u2013brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl\u2010F\u2010(D)L\u2010F\u2010(D)L\u2010F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)\u2010responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation\u2010related diseases.<\/jats:p>","DOI":"10.1002\/advs.202301348","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T14:39:21Z","timestamp":1682001561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia\u2010Reperfusion Injury"],"prefix":"10.1002","volume":"10","author":[{"given":"Qingchun","family":"Mu","sequence":"first","affiliation":[{"name":"The People's Hospital of Gaozhou Guangdong Medical University  Maoming 525200 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