{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:59:09Z","timestamp":1792900749305,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173763,91842305,81771686"],"award-info":[{"award-number":["82173763,91842305,81771686"]}],"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 Materials"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glioblastoma multiforme (GBM) is notoriously resistant to immunotherapy due to its intricate immunosuppressive tumor microenvironment (TME). Dysregulated cholesterol metabolism is implicated in the TME and promotes tumor progression. Here, it is found that cholesterol levels in GBM tissues are abnormally high, and glioma\u2010supportive macrophages (GSMs), an essential \u201ccholesterol factory\u201d, demonstrate aberrantly hyperactive cholesterol metabolism and efflux, providing cholesterol to fuel GBM growth and induce CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells exhaustion. Bioinformatics analysis confirms that high 7\u2010dehydrocholesterol reductase (DHCR7) level in GBM tissues associates with increased cholesterol biosynthesis, suppressed tumoricidal immune response, and poor patient survival, and DHCR7 expression level is significantly elevated in GSMs. Therefore, an intracavitary sprayable nanoregulator (NR)\u2010encased hydrogel system to modulate cholesterol metabolism of GSMs is reported. The degradable NR\u2010mediated ablation of DHCR7 in GSMs effectively suppresses cholesterol supply and activates T\u2010cell immunity. Moreover, the combination of Toll\u2010like receptor 7\/8 (TLR7\/8) agonists significantly promotes GSM polarization to antitumor phenotypes and ameliorates the TME. Treatment with the hybrid system exhibits superior antitumor effects in the orthotopic GBM model and postsurgical recurrence model. Altogether, the findings unravel the role of GSMs DHCR7\/cholesterol signaling in the regulation of TME, presenting a potential treatment strategy that warrants further clinical trials.\n                  <\/jats:p>","DOI":"10.1002\/adma.202311109","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T11:32:51Z","timestamp":1703158371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Intracavitary Spraying of Nanoregulator\u2010Encased Hydrogel Modulates Cholesterol Metabolism of Glioma\u2010Supportive Macrophage for Postoperative Glioblastoma Immunotherapy"],"prefix":"10.1002","volume":"36","author":[{"given":"Yuanmin","family":"Dong","sequence":"first","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  44 West Culture Road Jinan Shandong Province 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  44 West Culture Road Jinan Shandong Province 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  44 West Culture Road Jinan Shandong Province 250012 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