{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:46:39Z","timestamp":1781534799377,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2024NSCQ\u2010MSX0394"],"award-info":[{"award-number":["CSTB2024NSCQ\u2010MSX0394"]}],"id":[{"id":"10.13039\/501100005230","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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glioblastoma (GBM) presents significant challenges in treatment due to the presence of the blood\u2010brain barrier (BBB) and immunosuppressive tumor microenvironment (TME). Here, we developed a novel metal\u2010supramolecular delivery system (FLM@VC) that empowers meningeal lymphatic vessels\u00a0(MLVs)\u2010bridged intracranial\u2010peripheral dual immune modulation to reverse GBM immune suppression. Using coordination\u2010driven self\u2010assembly of lipoic acid (LA), iron ions (Fe\n                    <jats:sup>3+<\/jats:sup>\n                    ), and bovine albumin (BSA), we engineered nanoassemblies with Verubecestat (MK\u20108931) encapsulated and with vascular endothelial growth factor C (VEGF\u2010C) and c(RGDfK) conjugated. Subcutaneously delivered FLM@VC hijacks the MLVs for brain delivery bypassing the BBB, overcoming the limitations of conventional intravenous administration. Upon tumor accumulation, GSH\u2010responsive disassembly releases MK\u20108931 to reprogram TAMs from the pro\u2010tumoral M2 to the anti\u2010tumoral M1 phenotype, thereby eliciting proinflammatory cytokine secretion and enhancing phagocytic clearance of GBM cells. Concurrently, VEGF\u2010C\u2010mediated MLV expansion enhances dendritic cell (DC) trafficking to deep cervical lymph nodes (dCLNs), potently priming CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses. This MLVs\u2010bridged intracranial\u2010peripheral dual immunomodulation strategy effectively transforms immunologically \u201ccold\u201d GBM into \u201chot\u201d tumors, resulting in potent tumor eradication and significantly prolonged survival in orthotopic GBM models. It not only presents a novel paradigm for synergistic GBM immunotherapy but also provides an alternative brain drug delivery approach.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522604","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T18:46:12Z","timestamp":1770576372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metal\u2010Supramolecular Drug Delivery System Empowered Meningeal Lymphatic Vessels\u2010Bridged Intracranial\u2010Peripheral Dual Immune Modulation for Reversing Glioblastoma Immune Suppression"],"prefix":"10.1002","volume":"13","author":[{"given":"Chenxi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongsheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zening","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranran","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengchen","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuchi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7761-309X","authenticated-orcid":false,"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010024\u201001226\u2010x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21613"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c01253"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01402"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201005041\u2010y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010024\u201001544\u20107"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.02.009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3779\/j.issn.1009\u20103419.2023.106.07"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4185"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000520\u20105"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.217"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010021\u201000267\u20109"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010024\u201000829\u20107"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.01.056"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010019\u20100205\u2010x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425240903540205"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00007\u201010"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.03.002"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010023\u201000766\u20107"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.868986"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.12.058"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0030"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl7122"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3666"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.111972"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.09.022"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c16326"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.0c01806"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100368\u20108"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101912\u2010x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010022\u201000639\u20105"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202522604","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202522604","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202522604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T08:59:03Z","timestamp":1776416343000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202522604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,8]]},"references-count":31,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/advs.202522604"],"URL":"https:\/\/doi.org\/10.1002\/advs.202522604","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,8]]},"assertion":[{"value":"2025-11-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22604"}}