Lactoferrin Nanoparticle-Vanadium Complex: A Promising High-Efficiency Agent against Glioblastoma by Triggering Autophagy and Ferroptosis

Glioblastoma represents the most aggressive type of brain cancer with minimal clinical advancements in recent decades attributed to the absence of efficient drug delivery strategies. In this study, we synthesized a series of vanadium complexes (V1-V4) and then constructed a lactoferrin (LF)-V4 nanoparticle (NP) delivery system. The nanoplatform crossed the blood-brain barrier by binding to low-density lipoprotein receptor-associated protein-1 and selectively targeted glioblastoma, ultimately inhibiting the growth of in situ glioblastoma tumors. LF-V4 NPs induced autophagic cell death in U87-MG cells by generating reactive oxygen species (ROS) that damaged the mitochondria. Further studies revealed that LF-V4 NPs triggered lipid peroxidation through the accumulation of ROS, the depletion of GSH, and the downregulation of GPX4 and SLC7A11, ultimately leading to ferroptosis in glioblastoma cells.