{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:26:34Z","timestamp":1786976794922,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82222035"],"award-info":[{"award-number":["82222035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300462"],"award-info":[{"award-number":["82300462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402456"],"award-info":[{"award-number":["82402456"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515011290"],"award-info":[{"award-number":["2025A1515011290"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lung transplantation (LTx) is a life\u2010saving procedure for patients with end\u2010stage respiratory failure; however, primary graft dysfunction (PGD), primarily induced by ischemia\/reperfusion injury (IRI), remains a major complication. Although ex vivo lung perfusion (EVLP) improves preservation, clinical translation remains challenging owing to IRI complexity. Here, a novel approach is presented to mitigate lung IRI by developing of neutrophil\u2010derived ROS\u2010responsive cellular vesicles (SOD2\u2010Fer\u20101@CVs). This hybrid system integrates superoxide dismutase 2 (SOD2)\u2010overexpressing neutrophil nanovesicles with ROS\u2010responsive liposomes loaded with ferrostatin\u20101 (Fer\u20101), a potent ferroptosis inhibitor. SOD2\u2010Fer\u20101@CVs enabled targeted delivery to inflamed tissues and high oxidative stress environments, enabling ROS\u2010triggered release of SOD2 and Fer\u20101. The SOD2\u2010Fer\u20101@CVs system mechanistically targeted the core pathological pathways of IRI, including oxidative stress alleviation, adsorption and neutralization of pro\u2010inflammatory cytokines, ferroptosis suppression, and restoration of endothelial barrier integrity, with concurrent promotion of macrophage M2 polarization. Using the proprietary small\u2010animal EVLP platform, the therapeutic administration of SOD2\u2010Fer\u20101@CVs significantly mitigated of reperfusion\u2010related pathologies and improved graft performance, including enhanced oxygenation, reduced airway resistance, and restored lung compliance, attenuating lung injury after LTx. This study established a novel nanotherapeutic strategy that synergizes with EVLP to address multifactorial IRI, showing high translational potential for improving donor lung quality and LTx outcomes.<\/jats:p>","DOI":"10.1002\/advs.202506127","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T14:35:04Z","timestamp":1755182104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Engineering Neutrophil Vesicles for Synergistic Protection against Ischemia\/Reperfusion Injury after Lung Transplant"],"prefix":"10.1002","volume":"12","author":[{"given":"Hao\u2010Xiang","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease &amp; National Clinical Research Center for Respiratory Disease  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Yun","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute for Engineering Medicine Kunming Medical University  Kunming 650500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease &amp; National Clinical Research Center for Respiratory Disease  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Fang","family":"Meng","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology Shenzhen Bay Laboratory  Shenzhen 518132 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease &amp; National Clinical Research Center for Respiratory Disease  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease &amp; National Clinical Research Center for Respiratory Disease  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan\u2010Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease &amp; National Clinical Research Center for Respiratory Disease  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5010-0729","authenticated-orcid":false,"given":"Lang","family":"Rao","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology Shenzhen Bay Laboratory  Shenzhen 518132 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Jin","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute for Engineering Medicine Kunming Medical University  Kunming 650500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Xing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease &amp; National Clinical Research Center for Respiratory Disease  Guangzhou 510120 China"},{"name":"Southern Medical University  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2022.04.004"},{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","unstructured":"Medicine T L R Lancet Respir. Med2024 12 337.","DOI":"10.1016\/S2213-2600(24)00122-X"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.5500\/wjt.v13.i3.58"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000004503"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00121-2024"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061333"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13100859"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112739"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-023-01475-7"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0327"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061417"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2025.110943"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04601-w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02222-2019"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103231"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119402"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/ti.2024.12979"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.4285\/ctr.23.0057"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1390026"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1358153"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2024.149097"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13100859"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.2c00026"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2023.101942"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S457393"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202401369"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42155-z"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vesic.2022.100004"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkae062"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202402103"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-022-2328-x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02908-w"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1343364"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c02940"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c10784"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01953-8"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122718"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13103"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42958"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202307379"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202311803"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg3277"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.08.012"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S442727"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202406758"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1115603"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NH00070A"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2023.122071"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-024-01753-8"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/accountsmr.4c00362"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2017.1324730"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03263-8"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.81520"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-020-02556-3"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22454-z"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1142228"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.03.002"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2022.06.002"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.02.002"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0473"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3389\/ti.2024.13189"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.05.009"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezaf027"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202506127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:30:33Z","timestamp":1763119833000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202506127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":63,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/advs.202506127"],"URL":"https:\/\/doi.org\/10.1002\/advs.202506127","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"assertion":[{"value":"2025-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e06127"}}