{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:57:04Z","timestamp":1790798224824,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272571"],"award-info":[{"award-number":["82272571"]}],"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":["82372418"],"award-info":[{"award-number":["82372418"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Parkinson's disease (PD) is driven by neurodegeneration, iron accumulation, and microglial senescence, yet effective therapy is hindered by the blood\u2013brain barrier (BBB). By constructing the largest\u2010to\u2010date single\u2010cell atlas of the human substantia nigra, we identified a marked upregulation of PLXDC2 in PD microglia. Leveraging this finding, we developed a multifunctional biomimetic nanoplatform (HFn\u2010GM@siPLXDC2\/DFO\/CeO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010NP). This system co\u2010encapsulates the iron chelator deferoxamine and antioxidant CeO\n                    <jats:sub>2<\/jats:sub>\n                    nanoparticles, carries PLXDC2\u2010targeting siRNA, and features a ferritin\u2010modified microglial membrane coating to enhance BBB penetration and lesion targeting. In vivo, the nanoplatform efficiently traversed the BBB, reducing iron deposition and reactive oxygen species while suppressing microglial inflammation. Crucially, the treatment significantly alleviated dopaminergic neurodegeneration and improved motor performance\u2010including coordination, balance, and endurance in PD mice. Mechanistically, we demonstrate that PLXDC2 contributes to microglial senescence via the cGAS\u2010STING pathway, and its silencing attenuates neuroinflammation and oxidative stress. This study establishes a potent nanotherapeutic strategy integrating microenvironment remodeling with precise gene regulation to mitigate PD progression and alleviate motor deficits.\n                  <\/jats:p>","DOI":"10.1002\/advs.77793","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PLXDC2 siRNA\u2010Mediated Intervention Attenuates Microglial Senescence Through cGAS\u2010STING Signaling"],"prefix":"10.1002","author":[{"given":"Heyue","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Radiology Affiliated Hospital and Medical School of Nantong University  Nantong People's Republic of China"},{"name":"Research Center of Clinical Medicine Affiliated Hospital and Medical School of Nantong University  Nantong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University  Beijing People's Republic of China"},{"name":"Beijing Key Laboratory of Research and Translation for Drugs and Medical Devices in Precision Diagnosis and Treatment of Sports Injuries  Beijing People's Republic of China"},{"name":"Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Affiliated Hospital of Nantong University  Nantong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Nursing Peking University  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Ju","sequence":"additional","affiliation":[{"name":"Research Center of Clinical Medicine Affiliated Hospital and Medical School of Nantong University  Nantong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University  Beijing People's Republic of China"},{"name":"Beijing Key Laboratory of Research and Translation for Drugs and Medical Devices in Precision Diagnosis and Treatment of Sports Injuries  Beijing People's Republic of China"},{"name":"Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University  Beijing People's Republic of China"},{"name":"Beijing Key Laboratory of Research and Translation for Drugs and Medical Devices in Precision Diagnosis and Treatment of Sports Injuries  Beijing People's Republic of China"},{"name":"Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Center of Clinical Medicine Affiliated Hospital and Medical School of Nantong University  Nantong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University  Beijing People's Republic of China"},{"name":"Beijing Key Laboratory of Research and Translation for Drugs and Medical Devices in Precision Diagnosis and Treatment of Sports Injuries  Beijing People's Republic of China"},{"name":"Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Research Center of Clinical Medicine Affiliated Hospital and Medical School of Nantong University  Nantong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzheng","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Radiology Affiliated Hospital and Medical School of Nantong University  Nantong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianquan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University  Beijing People's Republic of China"},{"name":"Beijing Key Laboratory of Research and Translation for Drugs and Medical Devices in Precision Diagnosis and Treatment of Sports Injuries  Beijing People's Republic of China"},{"name":"Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University  Beijing People's Republic of China"},{"name":"Beijing Key Laboratory of Research and Translation for Drugs and Medical Devices in Precision Diagnosis and Treatment of Sports Injuries  Beijing People's Republic of China"},{"name":"Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University  Huai'an People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(16)30230\u20107"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00218\u2010X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.131045"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-1777775"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)01419\u20108"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-223176"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2024.120547"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102032"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12071012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.05.044"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010024\u201002587\u20101"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.06.023"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2025.161251"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010025\u201001499\u20106"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010021\u201003262\u20109"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0BM01726D"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106934"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010019\u20100619\u20100"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010023\u201000699\u20100"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010024\u201001590\u20101"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi8287"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1390310"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2021.01.003"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209254"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c20492"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b08785"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202005562"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b06969"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010025\u201003646\u2010x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114485"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201801362"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003937"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201011220\u20101"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-025-00737-7"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023311\u20109"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201031799\u2010y"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(21)00030\u20102"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02741387"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084176"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102477"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102077"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103787"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020537"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010018\u20100242\u2010x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.07.003"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071468"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002807"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.01.011"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010019\u20100566\u20101"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9080743"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR\u2010D\u201024\u201000245"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj2102"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77793","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77793","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:09:52Z","timestamp":1790795392000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":54,"alternative-id":["10.1002\/advs.77793"],"URL":"https:\/\/doi.org\/10.1002\/advs.77793","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2025-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77793"}}