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In this study, supramolecular nanoscavengers are engineered by harnessing the intrinsic binding affinity between endogenous small\u2010molecule cholesterol and \u03b2\u2010cyclodextrin (\u03b2\u2010CD). This host\u2010guest interaction enabled both targeted drug release and cholesterol clearance through competitive displacement within the cholesterol\u2010rich microenvironment of GBM. Consequently, tumor\u2010associated cholesterol dysregulation is effectively disrupted, resulting in significant inhibition of cellular proliferation and invasion. Furthermore, the supramolecular nanoscavengers interfered with the metabolic crosstalk between tumor cells and immune cells involving cholesterol, thereby remodeling the immunosuppressive tumor microenvironment and demonstrating substantial therapeutic efficacy in vivo. Additionally, the dynamic and reversible binding between \u03b2\u2010CD and various guest molecules facilitated efficient delivery of the supramolecular host to the central nervous system (CNS). Collectively, these findings presented a promising strategy for targeting cholesterol as an intervention in the treatment of GBM as well as other CNS disorders associated with altered cholesterol metabolism.<\/jats:p>","DOI":"10.1002\/advs.202519690","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:24:19Z","timestamp":1763706259000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Supramolecular Nanoscavengers: Based \u201cCargo\u2010Exchange\u201d Breaking Cholesterol Metabolic Dysregulation for Glioblastoma Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Zonghua","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongrui","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1049-1216","authenticated-orcid":false,"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Brain Function and Disorders  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01772-0"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03224-y"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.12.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00529-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03607-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201606"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0150-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40880-018-0301-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03490-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105215"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307023"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu148"},{"key":"e_1_2_8_13_1","first-page":"880","volume":"21","author":"Crunkhorn S.","year":"2022","journal-title":"Nat. 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