T-0901317

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.

Tendon injuries often disrupt lipid metabolism, leading to cholesterol accumulation and compromised collagen fiber development, thus hindering effective healing.However, the effects of lipid deposition in the process of tendon defect repair using biomaterials remain unclear.In this study, immature collagen structure and lipid accumulation were confirmed in injured tendon.Proteomic anal. identified apolipoprotein E (ApoE) as a key modulator of lipid metabolism in tendon injury.Using ApoE-knockout mice fed a high-fat diet, the role of ApoE in promoting tendon tissue development was verified.A rat Achilles tendon defect model was used to examine the therapeutic effects of T0901317-loaded polycaprolactone-poly(L-lactide-co-caprolactone)-Gelatin (PPG) nanofibers, designed for localized, sustained release of T0901317 to enhance ApoE expression and regulate lipid metabolism at the injury site.The application of T0901317-loaded PPG nanofibers effectively reduced lipid deposition and inhibited ectopic ossification and chondrogenesis, leading to promoted collagen maturation and enhanced biomech. properties of regenerated tendon tissue.KEGG pathway anal. indicated that ApoE regulated inflammation via the NF-κB pathway, modulating IL-6, TGF-β, and angiogenesis.These findings demonstrate the therapeutic potential of targeting lipid metabolism through localized drug delivery systems, such as T0901317-loaded PPG nanofibers, as a promising approach for improving tendon repair and regeneration.