Ginsenoside F2-modified liposomes delivering FTY720 enhance glioblastoma targeting and antitumor activity via ferroptosis

作者：Huizhe Xu, Zhisheng Wu, Jiamei Tang, Yu Gan, Ji‐Cheng Li, Yingying Yu, Yi Chen, Rui Sui, Jia Liu, Ye Zhang, Haozhe Piao · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156917 · 被引用次数：7 · 研究领域：Sphingolipid Metabolism and Signaling、Ferroptosis and cancer prognosis、Ginseng Biological Effects and Applications

BACKGROUND: Glioblastoma (GBM) is the most malignant primary intracranial tumor. Owing to its unfavorable prognosis and frequent recurrence, patient outcomes are poor even with standard treatment. Recent studies have reported that FTY720, a structurally modified sphingosine extracted from Cordyceps sinensis, has preclinical antitumor efficacy and can regulate the microenvironment of GBM. However, the mechanism and effective utilization of FTY720, i.e., avoiding adverse reactions during systemic application in GBM remain unclear. PURPOSE: This study aimed to investigate the mechanisms by which FTY720 suppresses GBM growth and to explore the ability of a novel liposomal nanoparticle carrying FTY720 to directly target GBM. METHODS: Molecular, cytological, and histological techniques were employed to assess the effects of FTY720 on GBM cells, both in vitro and in vivo. Ferroptosis induction and its regulatory mechanisms were explored using a combination of reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) assays; transmission electron microscopy (TEM); and orthotopic GBM mouse model experiments. A nanoparticle drug delivery system based on liposomes (GF2-FTY720-LPs) was synthesized by thin film dispersion. RESULTS: Our study revealed that FTY720 induces ferroptosis in GBM cells through the AMPK-mTOR-GPX4 pathway, and that ginsenoside F2 (GF2) plays a synergistic role by reducing GSH levels. GF2-FTY720-LPs show superior targeting ability and potent inhibit...