{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:00:04Z","timestamp":1785308404631,"version":"3.55.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cerebral ischemia reperfusion injury (CIRI) after stroke is hard to treat because the blood\u2013brain barrier (BBB) blocks most drugs, while reperfusion triggers oxidative stress, ferroptosis, and neuroinflammation. We designed a neutrophil hitchhiking lipid nanoparticle (RKH Neu@Mino) by conjugating an RKH peptide (from Akkermansia muciniphila) onto DSPE PEG maleimide and encapsulating minocycline via microfluidic assembly. The nanoparticles specifically bind to neutrophil TLR4, allowing activated neutrophils to ferry them across the BBB and into ischemic lesions. Once there, RKH Neu@Mino suppresses ROS burst, inhibits ferroptosis, and shifts microglial polarization from pro inflammatory M1 to protective M2 phenotype, thereby mitigating CIRI. This neutrophil hitchhiking strategy offers a powerful approach to overcome the BBB delivery hurdle and treat post stroke reperfusion injury.<\/jats:p>","DOI":"10.3389\/fphar.2026.1888834","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:03:48Z","timestamp":1785305028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil-hitchhiking nanoplatform overcomes blood\u2013brain barrier to treat cerebral ischemia-reperfusion injury via ferroptosis inhibition and microglial modulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Shenggang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchun","family":"Mu","sequence":"additional","affiliation":[{"name":"Gaozhou People\u2019s Hospital, Guangdong Medical University","place":["Maoming, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Mudanjiang Medical University","place":["Mudanjiang, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longguang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Center for Regenerative and Aging Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","place":["Yiwu, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suji","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.3390\/pharmaceutics15122658","article-title":"Drug delivery to the brain: recent advances and unmet challenges","volume":"15","author":"Bhunia","year":"2023","journal-title":"Pharmaceutics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/s41419-019-1553-x","article-title":"Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoids","volume":"10","author":"Boisvert","year":"2019","journal-title":"Cell. 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