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journal article·2025-05Open access

HDL Nanodiscs Loaded with Liver X Receptor Agonist Decreases Tumor Burden and Mediates Long‐term Survival in Mouse Glioma Model

Troy A. Halseth, Anzar A. Mujeeb, Lisha Liu, Kaushik Banerjee, Nigel Lang, Todd Hollon, Minzhi Yu, Mark Vander Roest, Ling Mei, Hongliang He, Maya Sheth, Maria G. Castro, Anna Schwendeman

Small· Volume 21· Issue 20
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Abstract

Abstract Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor with a 5‐year survival rate of 7%. 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‐density lipoprotein (sHDL) nanodiscs delivering Liver‐X‐Receptor (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‐like receptor 9 pathway. In the present study, treatment with GW‐CpG‐sHDL nanodiscs increases the expression of cholesterol efflux transporters on murine GL261 cells leading to enhanced cholesterol removal. Experiments in GL261‐tumor‐bearing mice reveal combining GW‐CpG‐sHDL nanodiscs with radiation (IR) therapy significantly increases median survival compared to GW‐CpG‐sHDL or IR alone. Furthermore, 66% of long‐term survivors from the GW‐CpG‐sHDL +IR treatment group show no tumor tissue when rechallenged.
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Research context

Nanomaterials

OpenAlex topics: Cancer, Lipids, and Metabolism · Cholesterol and Lipid Metabolism · Drug Transport and Resistance Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Medicinal Chemistry College of Pharmacy University of Michigan 428 Church St Ann Arbor MI 48109 USA

Department of Neurosurgery University of Michigan Medical School Ann Arbor Michigan 48109 USA

Department of Cell and Developmental Biology University of Michigan Medical School Ann Arbor MI 48109 USA

Department of Pharmaceutics School of Pharmacy China Pharmaceutical University Nanjing 210009 China

Department of Pharmaceutical Sciences College of Pharmacy University of Michigan 428 Church St Ann Arbor MI 48109 USA

Engineering Research Center for Pharmaceuticals and Equipment of Sichuan Province Sichuan Industrial Institute of Antibiotics School of Pharmacy Chengdu University Chengdu 610106 China

State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China

Biointerfaces Institute NCRC 2800 Plymouth Rd Ann Arbor MI 48109 USA

Funding

National Institutes of Health · ChadTough Foundation · Ian's Friends Foundation · Leah's Happy Hearts · Pediatric Brain Tumor Foundation · American Heart Association · Pharmaceutical Research and Manufacturers of America Foundation

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