{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:07:29Z","timestamp":1784246849315,"version":"3.55.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":163,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471330"],"award-info":[{"award-number":["82471330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Project of Tongren City, Guizhou Province","award":["68"],"award-info":[{"award-number":["68"]}]},{"name":"Guizhou Provincial Science and Technology Innovation Leading Talent Workstation for Stroke Brain Injury","award":["KXZ[2025]051"],"award-info":[{"award-number":["KXZ[2025]051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ischemic stroke is a major cause of death and long-term disability worldwide, in which oxidative stress and neuroinflammation contribute substantially to secondary neuronal injury. Edaravone (EDA), a clinically approved free radical scavenger, has shown neuroprotective potential in ischemic stroke; however, its therapeutic efficacy is hindered by a short half-life, limited blood\u2013brain barrier penetration and off-target effects. To overcome these limitations, we developed a biomimetic nanoplatform by encapsulating EDA within a nanoparticle (NP) core and coating it with membranes derived from M2-polarized microglia (EDA@M2 NPs). This hybrid system integrates potent antioxidant activity with inflammation-targeting and immunomodulatory capabilities. In a mouse model of middle cerebral artery occlusion, EDA@M2 NPs selectively accumulated in the ischemic hemisphere, significantly reduced infarct volume, suppressed neuronal apoptosis and improved neurological outcomes. Mechanistically, the nanoplatform not only scavenged excessive reactive oxygen species but also reprogrammed microglia from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby mitigating secondary neuroinflammation. By integrating targeted delivery, oxidative stress attenuation and immune microenvironment remodeling, this combinatorial therapeutic strategy markedly enhanced neuroprotection after ischemic stroke. Our findings demonstrate the translational promise of biomimetic nanotherapeutics for effective ischemic brain injury intervention.<\/jats:p>","DOI":"10.1093\/rb\/rbag119","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T16:06:37Z","timestamp":1781453197000},"source":"Crossref","is-referenced-by-count":0,"title":["Biomimetic M2 microglia membrane-coated nanoplatform for immune reprogramming and targeted edaravone delivery in ischemic stroke"],"prefix":"10.1093","volume":"13","author":[{"given":"Yanhong","family":"Ren","sequence":"first","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Joint Innovation Center for Brain Disorders, Capital Medical University , Beijing 100069,","place":["China"]},{"name":"Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University , Xuzhou 221002,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University , Xuzhou 221002,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, People\u2019s Hospital of Tongren , Guizhou 554300,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, People\u2019s Hospital of Tongren , Guizhou 554300,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University , Xuzhou 221002,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Joint Innovation Center for Brain Disorders, Capital Medical University , Beijing 100069,","place":["China"]},{"name":"Department of Ophthalmology, People\u2019s Hospital of Tongren , Guizhou 554300,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"2026071620013763500_rbag119-B1","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1016\/S2468-2667(21)00230-9","article-title":"Primary stroke prevention worldwide: translating evidence into action","volume":"7","author":"Owolabi","year":"2022","journal-title":"Lancet Public Health"},{"key":"2026071620013763500_rbag119-B2","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1161\/STROKEAHA.110.612358","article-title":"Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years","volume":"42","author":"Adeoye","year":"2011","journal-title":"Stroke"},{"key":"2026071620013763500_rbag119-B3","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S1474-4422(22)00519-1","article-title":"Thrombolysis for acute ischaemic stroke: current status and future perspectives","volume":"22","author":"Tsivgoulis","year":"2023","journal-title":"Lancet Neurol"},{"key":"2026071620013763500_rbag119-B4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.pharmthera.2018.09.005","article-title":"Neutrophils in tPA-induced hemorrhagic transformations: main culprit, accomplice or innocent bystander?","volume":"194","author":"Ouk","year":"2019","journal-title":"Pharmacol Ther"},{"key":"2026071620013763500_rbag119-B5","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1002\/ptr.7843","article-title":"Effects of intravenous thrombolysis with and without salvianolic acids for injection on the functional recovery of patients with acute ischemic stroke: a systematic review, meta-analysis, and trial sequential analysis","volume":"37","author":"Wang","year":"2023","journal-title":"Phytother Res"},{"key":"2026071620013763500_rbag119-B6","doi-asserted-by":"crossref","first-page":"107695","DOI":"10.1016\/j.pharmthera.2020.107695","article-title":"Natural medicine in neuroprotection for ischemic stroke: challenges and prospective","volume":"216","author":"Tao","year":"2020","journal-title":"Pharmacol Ther"},{"key":"2026071620013763500_rbag119-B7","doi-asserted-by":"crossref","first-page":"103185","DOI":"10.1016\/j.redox.2024.103185","article-title":"Developing targeted antioxidant nanomedicines for ischemic penumbra: novel strategies in treating brain ischemia-reperfusion injury","volume":"73","author":"Hou","year":"2024","journal-title":"Redox Biol"},{"key":"2026071620013763500_rbag119-B8","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1186\/s12951-024-02772-2","article-title":"Targeted pathophysiological treatment of ischemic stroke using nanoparticle-based drug delivery system","volume":"22","author":"Liu","year":"2024","journal-title":"J Nanobiotechnology"},{"key":"2026071620013763500_rbag119-B9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1161\/STROKEAHA.124.049013","article-title":"Cerebral infarct growth: pathophysiology, pragmatic assessment, and clinical implications","volume":"56","author":"Pensato","year":"2025","journal-title":"Stroke"},{"key":"2026071620013763500_rbag119-B10","doi-asserted-by":"crossref","first-page":"113125","DOI":"10.1016\/j.biopha.2022.113125","article-title":"Glutamate excitotoxicity: potential therapeutic target for ischemic stroke","volume":"151","author":"Shen","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"2026071620013763500_rbag119-B11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.apsb.2024.10.004","article-title":"Oxidative stress and inflammation in the pathogenesis of neurological disorders: mechanisms and implications","volume":"15","author":"Dash","year":"2025","journal-title":"Acta Pharm Sin B"},{"key":"2026071620013763500_rbag119-B12","doi-asserted-by":"crossref","first-page":"e2312897","DOI":"10.1002\/adma.202312897","article-title":"Blood-brain barrier-penetrating and lesion-targeting nanoplatforms inspired by the pathophysiological features for synergistic ischemic stroke therapy","volume":"36","author":"Tang","year":"2024","journal-title":"Adv Mater"},{"key":"2026071620013763500_rbag119-B13","doi-asserted-by":"crossref","first-page":"e2210144","DOI":"10.1002\/adma.202210144","article-title":"A thrombin-activated peptide-templated nanozyme for remedying ischemic stroke via thrombolytic and neuroprotective actions","volume":"36","author":"Wang","year":"2024","journal-title":"Adv Mater"},{"key":"2026071620013763500_rbag119-B14","first-page":"38","article-title":"ROS-responsive 18\u03b2-glycyrrhetic acid-conjugated polymeric nanoparticles mediate neuroprotection in ischemic stroke through HMGB1 inhibition and microglia polarization regulation","volume":"19","author":"Jin","year":"2023","journal-title":"Bioact Mater"},{"key":"2026071620013763500_rbag119-B15","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1038\/s41467-025-57774-x","article-title":"Edaravone dexborneol for ischemic stroke with sufficient recanalization after thrombectomy: a randomized phase II trial","volume":"16","author":"Chen","year":"2025","journal-title":"Nat Commun"},{"key":"2026071620013763500_rbag119-B16","first-page":"CD007230","article-title":"Edaravone for acute ischaemic stroke","volume":"2011","author":"Feng","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"2026071620013763500_rbag119-B17","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s11011-025-01559-0","article-title":"Edaravone dextranol alleviates ferroptosis, cuproptosis, and blood-brain barrier damage after acute cerebral infarction","volume":"40","author":"Jin","year":"2025","journal-title":"Metab Brain Dis"},{"key":"2026071620013763500_rbag119-B18","first-page":"126","article-title":"Targeted alleviation of ischemic stroke reperfusion via atorvastatin-ferritin Gd-layered double hydroxide","volume":"20","author":"Wang","year":"2023","journal-title":"Bioact Mater"},{"key":"2026071620013763500_rbag119-B19","first-page":"100886","article-title":"Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury","volume":"19","author":"Zhang","year":"2024","journal-title":"Asian J Pharm Sci"},{"key":"2026071620013763500_rbag119-B20","doi-asserted-by":"crossref","first-page":"e2401462","DOI":"10.1002\/adhm.202401462","article-title":"Phosphorus dendrimers Co-deliver fibronectin and edaravone for combined ischemic stroke treatment via cooperative modulation of microglia\/neurons and vascular regeneration","volume":"13","author":"Ma","year":"2024","journal-title":"Adv Healthc Mater"},{"key":"2026071620013763500_rbag119-B21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.freeradbiomed.2024.03.019","article-title":"Edaravone dexborneol protects against cerebral ischemia\/reperfusion-induced blood-brain barrier damage by inhibiting ferroptosis via activation of nrf-2\/HO-1\/GPX4 signaling","volume":"217","author":"Xiao","year":"2024","journal-title":"Free Radic Biol Med"},{"key":"2026071620013763500_rbag119-B22","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1161\/STROKEAHA.120.031197","article-title":"Edaravone dexborneol versus edaravone alone for the treatment of acute ischemic stroke: a phase III, randomized, double-blind, comparative trial","volume":"52","author":"Xu","year":"2021","journal-title":"Stroke"},{"key":"2026071620013763500_rbag119-B23","first-page":"19","article-title":"Immune cells: potential carriers or agents for drug delivery to the central nervous system","volume":"11","author":"Zhang","year":"2024","journal-title":"Mil Med Res"},{"key":"2026071620013763500_rbag119-B24","doi-asserted-by":"crossref","first-page":"e2301779","DOI":"10.1002\/adma.202301779","article-title":"Bacteria-derived outer-membrane vesicles hitchhike neutrophils to enhance ischemic stroke therapy","volume":"35","author":"Pan","year":"2023","journal-title":"Adv Mater"},{"key":"2026071620013763500_rbag119-B25","first-page":"230","article-title":"C-176 loaded Ce DNase nanoparticles synergistically inhibit the cGAS-STING pathway for ischemic stroke treatment","volume":"29","author":"Zhu","year":"2023","journal-title":"Bioact Mater"},{"key":"2026071620013763500_rbag119-B26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pneurobio.2016.05.001","article-title":"Functions and mechanisms of microglia\/macrophages in neuroinflammation and neurogenesis after stroke","volume":"142","author":"Xiong","year":"2016","journal-title":"Prog Neurobiol"},{"key":"2026071620013763500_rbag119-B27","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.biomaterials.2019.04.026","article-title":"Scaffolds biomimicking macrophages for a glioblastoma NIR-Ib imaging guided photothermal therapeutic strategy by crossing blood-brain barrier","volume":"211","author":"Lai","year":"2019","journal-title":"Biomaterials"},{"key":"2026071620013763500_rbag119-B28","doi-asserted-by":"crossref","first-page":"23746","DOI":"10.1021\/acsnano.3c07555","article-title":"Biomimetic macrophage membrane-camouflaged nanoparticles induce ferroptosis by promoting mitochondrial damage in glioblastoma","volume":"17","author":"Cao","year":"2023","journal-title":"ACS Nano"},{"key":"2026071620013763500_rbag119-B29","doi-asserted-by":"crossref","first-page":"e2101526","DOI":"10.1002\/advs.202101526","article-title":"Macrophage-disguised manganese dioxide nanoparticles for neuroprotection by reducing oxidative stress and modulating inflammatory microenvironment in acute ischemic stroke","volume":"8","author":"Li","year":"2021","journal-title":"Adv Sci"},{"key":"2026071620013763500_rbag119-B30","doi-asserted-by":"crossref","first-page":"eado6798","DOI":"10.1126\/sciadv.ado6798","article-title":"Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis","volume":"10","author":"Luo","year":"2024","journal-title":"Sci Adv"},{"key":"2026071620013763500_rbag119-B31","doi-asserted-by":"crossref","first-page":"e2300326","DOI":"10.1002\/smll.202300326","article-title":"M2 macrophage membrane-mediated biomimetic-nanoparticle carrying COX-siRNA targeted delivery for prevention of tendon adhesions by inhibiting inflammation","volume":"19","author":"Sun","year":"2023","journal-title":"Small"},{"key":"2026071620013763500_rbag119-B32","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1161\/STROKEAHA.112.659656","article-title":"Microglia\/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia","volume":"43","author":"Hu","year":"2012","journal-title":"Stroke"},{"key":"2026071620013763500_rbag119-B33","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.jconrel.2024.11.033","article-title":"Exploration of M2 macrophage membrane as a biotherapeutic agent and strong synergistic therapeutic effects in ischemic stroke","volume":"378","author":"Zhang","year":"2025","journal-title":"J Control Release"},{"key":"2026071620013763500_rbag119-B34","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.7150\/thno.68895","article-title":"M2 microglia-derived extracellular vesicles promote white matter repair and functional recovery via miR-23a-5p after cerebral ischemia in mice","volume":"12","author":"Li","year":"2022","journal-title":"Theranostics"},{"key":"2026071620013763500_rbag119-B35","doi-asserted-by":"crossref","first-page":"e2305659","DOI":"10.1002\/smll.202305659","article-title":"Engineered macrophage membrane-coated nanoparticles with enhanced CCR2 expression promote spinal cord injury repair by suppressing neuroinflammation and neuronal death","volume":"20","author":"Gu","year":"2024","journal-title":"Small"},{"key":"2026071620013763500_rbag119-B36","doi-asserted-by":"crossref","first-page":"e202400410","DOI":"10.1002\/cmdc.202400410","article-title":"Biomimetic cell membrane-coated nanoparticles for cancer theranostics","volume":"19","author":"Jiang","year":"2024","journal-title":"ChemMedChem"},{"key":"2026071620013763500_rbag119-B37","doi-asserted-by":"crossref","first-page":"114040","DOI":"10.1016\/j.intimp.2025.114040","article-title":"Hydroxysafflor yellow a attenuates the inflammatory response in cerebral ischemia-reperfusion injured mice by regulating microglia polarization per SIRT1-mediated HMGB1\/NF-\u03baB signaling pathway","volume":"147","author":"Yao","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"2026071620013763500_rbag119-B38","doi-asserted-by":"crossref","first-page":"122036","DOI":"10.1016\/j.biomaterials.2023.122036","article-title":"Activated macrophage membrane-coated nanoparticles relieve osteoarthritis-induced synovitis and joint damage","volume":"295","author":"Zhou","year":"2023","journal-title":"Biomaterials"},{"key":"2026071620013763500_rbag119-B39","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1136\/svn-2024-003442","article-title":"Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation","volume":"10","author":"Liu","year":"2025","journal-title":"Stroke Vasc Neurol"},{"key":"2026071620013763500_rbag119-B40","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.3390\/ijms23042223","article-title":"Cell membrane-cloaked nanotherapeutics for targeted drug delivery","volume":"23","author":"Lee","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026071620013763500_rbag119-B41","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.1021\/acsnano.1c10635","article-title":"Nanotechnology tools enabling biological discovery","volume":"16","author":"Salvador-Morales","year":"2022","journal-title":"ACS Nano"},{"key":"2026071620013763500_rbag119-B42","doi-asserted-by":"crossref","first-page":"e20240957","DOI":"10.1084\/jem.20240957","article-title":"Targeting CD206+ macrophages disrupts the establishment of a key antitumor immune axis","volume":"222","author":"Ray","year":"2025","journal-title":"J Exp Med"},{"key":"2026071620013763500_rbag119-B43","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.7150\/thno.81520","article-title":"Cell-membrane-coated nanoparticles for the fight against pathogenic bacteria, toxins, and inflammatory cytokines associated with sepsis","volume":"13","author":"Wang","year":"2023","journal-title":"Theranostics"},{"key":"2026071620013763500_rbag119-B44","doi-asserted-by":"crossref","first-page":"5689","DOI":"10.1038\/s41467-024-50021-9","article-title":"Hematopoietic stem and progenitor cell membrane-coated vesicles for bone marrow-targeted leukaemia drug delivery","volume":"15","author":"Li","year":"2024","journal-title":"Nat Commun"},{"key":"2026071620013763500_rbag119-B45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12951-023-02255-w","article-title":"M2 microglia-derived exosome-loaded electroconductive hydrogel for enhancing neurological recovery after spinal cord injury","volume":"22","author":"Guan","year":"2024","journal-title":"J Nanobiotechnology"},{"key":"2026071620013763500_rbag119-B46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cytogfr.2024.06.002","article-title":"The impact of cytokines in neuroinflammation-mediated stroke","volume":"78","author":"Kumari","year":"2024","journal-title":"Cytokine Growth Factor Rev"},{"key":"2026071620013763500_rbag119-B47","doi-asserted-by":"crossref","first-page":"1047550","DOI":"10.3389\/fimmu.2022.1047550","article-title":"The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: a review","volume":"13","author":"Zeng","year":"2022","journal-title":"Front Immunol"},{"key":"2026071620013763500_rbag119-B48","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.7150\/thno.99822","article-title":"Microenvironment-responsive nanosystems for ischemic stroke therapy","volume":"14","author":"Wu","year":"2024","journal-title":"Theranostics"}],"container-title":["Regenerative Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/rb\/advance-article-pdf\/doi\/10.1093\/rb\/rbag119\/68522835\/rbag119.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/rb\/article-pdf\/doi\/10.1093\/rb\/rbag119\/68522835\/rbag119.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/rb\/article-pdf\/doi\/10.1093\/rb\/rbag119\/68522835\/rbag119.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:01:50Z","timestamp":1784246510000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/rb\/article\/doi\/10.1093\/rb\/rbag119\/8707645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":48,"URL":"https:\/\/doi.org\/10.1093\/rb\/rbag119","relation":{},"ISSN":["2056-3418","2056-3426"],"issn-type":[{"value":"2056-3418","type":"print"},{"value":"2056-3426","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"rbag119"}}