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We developed apolipoprotein B fragment\u2010decorated nanoparticles co\u2010loaded with regorafenib and erythrodiol (ApoBf\u2010R\/E@NPs), a low\u2010density lipoprotein receptor\u2010oriented biomimetic nanoplatform that couples brain\u2010tumor delivery with coordinated dual\u2010drug exposure. Fixed\u2010ratio combination\u2010index analysis demonstrated synergy between the two agents. Regorafenib disrupts autophagy\u2010associated nutrient salvage and restricts angiogenic support, whereas erythrodiol stabilizes ATP\u2010binding cassette transporter A1 and depletes cellular cholesterol. These complementary perturbations converge on ATP depletion, mitochondrial dysfunction, and suppression of phosphoinositide 3\u2010kinase\/protein kinase B and mitogen\u2010activated protein kinase signaling. Across established and patient\u2010derived GBM models, treatment broadly impaired tumor\u2010cell survival while suppressing stemness\u2010associated programs and reducing viability and tumorsphere persistence in patient\u2010derived glioma stem\u2010like cell cultures. Treatment also promoted an immunogenic cell death\u2010associated tumor\u2010cell state and antitumor immune remodeling. In immunocompetent GBM models, ApoBf\u2010R\/E@NPs showed preferential intracranial tumor\u2010associated delivery, suppressed orthotopic and untreated distal tumor growth, and delayed postoperative regrowth, accompanied by systemic immune remodeling and expansion of memory\u2010associated T\u2010cell populations. These findings establish a blood\u2010brain barrier\u2010oriented nanodelivery strategy that couples complementary metabolic vulnerabilities to broad GBM control, stem\u2010like compartment suppression, and antitumor immunity.<\/jats:p>","DOI":"10.1002\/advs.78189","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:03:22Z","timestamp":1791774202000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low\u2010Density Lipoprotein Receptor\u2010Targeted Biomimetic Nanoplatform Suppresses Glioblastoma Stemness and Remodels Antitumor Immunity via Dual Metabolic Disruption"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-387X","authenticated-orcid":false,"given":"Yining","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Translational Medicine Research Institute First Hospital of Jilin University Changchun People's 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