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Previous studies have shown that GBM tumors have a reduced capacity to produce cholesterol and instead depend on the uptake of cholesterol produced by astrocytes. To target cholesterol metabolism to induce cancer cell death, synthetic high\u2010density lipoprotein (sHDL) nanodiscs delivering Liver\u2010X\u2010Receptor (LXR) agonists and CpG oligonucleotides for targeting GBM are investigated. LXR agonists synergize with sHDL nanodiscs by increasing the expression of the ABCA1 cholesterol efflux transporter, resulting in further depletion of cholesterol reserves within tumors, and CpG oligonucleotides are established adjuvants used in cancer immunotherapy that work through the toll\u2010like receptor 9 pathway. In the present study, treatment with GW\u2010CpG\u2010sHDL nanodiscs increases the expression of cholesterol efflux transporters on murine GL261 cells leading to enhanced cholesterol removal. 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Furthermore, 66% of long\u2010term survivors from the GW\u2010CpG\u2010sHDL +IR treatment group show no tumor tissue when rechallenged.<\/jats:p>","DOI":"10.1002\/smll.202307097","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T04:59:14Z","timestamp":1747371554000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["HDL Nanodiscs Loaded with Liver X Receptor Agonist Decreases Tumor Burden and Mediates Long\u2010term Survival in Mouse Glioma Model"],"prefix":"10.1002","volume":"21","author":[{"given":"Troy A.","family":"Halseth","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry College of Pharmacy University of Michigan  428 Church St Ann Arbor MI 48109 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anzar A.","family":"Mujeeb","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Michigan Medical 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