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Here, based on the finding that CD93 is exclusively up\u2010regulated on glioma\u2010associated vascular endothelial cells (VECs), small extracellular vesicles (sEVs) were modified with insulin\u2010like growth factor\u2010binding protein 7 (IGFBP7), a natural ligand of CD93, to create a delivery platform that can deliver therapeutic agents to glioma\u2010associated VECs with high efficiency. At markedly reduced intravenous doses, IGFBP7\u2010sEVs efficiently concentrated temozolomide (TMZ) within glioma and elicited pronounced tumor growth inhibition. More strikingly, systemic administration of stimulator of interferon genes (STING) agonist\u2010loaded IGFBP7\u2010sEVs outperformed direct intratumoral injection of free STING agonist: the glioma microenvironment (GME) was extensively remodeled and antigen\u2010presenting capacity of myeloid cells was markedly enhanced. Moreover, endothelial\u2010restricted STING activation attenuated the exhaustion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Consequently, the intensity of the tumor\u2010specific immune response was markedly augmented. Our data suggest that IGFBP7\u2010modified sEVs represent a novel platform that enables highly efficient, glioma VECs\u2010targeted delivery of therapeutics into glioma, and are adaptable to a broad spectrum of agents, especially immunomodulators. It is a novel and effective strategy for treating gliomas.\n                  <\/jats:p>","DOI":"10.1002\/advs.202518490","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:21:41Z","timestamp":1769062901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Engineered Small Extracellular Vesicles Targeting Tumor\u2010Associated Endothelial Cells to Effectively Remodel the Glioma Microenvironment"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2467-8664","authenticated-orcid":false,"given":"Lingling","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Burns and Cutaneous Surgery Xijing Hospital Fourth Military Medical University  Xi'an Shaanxi China"},{"name":"Laboratory of Gene Therapy Department of Biochemistry College of Life Sciences Shaanxi Normal University  Xi'an Shaanxi 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