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.