A functional carbon dots induce ferroptosis by suppressing PLPP4 activity to inhibit glioblastoma growth

[Display omitted] •A novel carbon dots (MGA-CDs) from metformin and gallic acid.•MGA-CDs inhibits glioblastoma growth via a new ferroptosis suppressor PLPP4.•The disorder of glycerophospholipid metabolism is a new ferroptosis mechanism.•A strategy to expand MGA-CDs-based therapeutic agent for glioblastoma. Glioblastoma is a fatal primary brain cancer lacking effective therapeutic drugs. The presence of the blood–brain barrier (BBB) severely hinders the delivery of drugs to the brain. In recent years, nanoparticles, especially carbon dots (CDs), are promising drug delivery strategy for CNS diseases. Here, we synthesized a novel carbon dots（MGA-CDs）for glioblastoma treatment by hydrothermal method using metformin and gallic acid as precursor. MGA-CDs shows dominant BBB permeability and sensitive anti-tumor activity. In addition, MGA-CDs exhibits significant capability of targeting tumor cells mitochondria without the aid of anyextra targeting molecules, resulting in the shrunken of mitochondria and reduced numbers of mitochondrial cristae. Transcriptome profiling suggested that MGA-CDs disturbs the glycerophospholipid metabolism pathway by inhibiting the expression of PLPP4, thereby inducing ferroptosis. The efficient therapeutic potency of MGA-CDs is further confirmed in human-derived orthotopic glioblastoma mice model. MGA-CDs significantly inhibited the growth of intracranial tumors and prolonged the survival of tumor-bearing mice. This work presents a viable strategy that development of CDs-based novel therapeutic agent for glioblastoma.