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Updated: Jul 1, 2026

Revealing the Ferroptotic Phenotype of Medulloblastoma
04:01

Revealing the Ferroptotic Phenotype of Medulloblastoma

Published on: March 15, 2024

Metal-organic framework-based fuel-driven chemical reaction network for ferroptosis therapy

Ding Guo1,2, Qian Lin1, Quanyi Jin1

  • 1Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, PR China.

Journal of Nanobiotechnology
|June 29, 2026
PubMed

Insights

This study introduces novel nanoparticles that overcome cancer's ferroptosis defenses by inhibiting multiple pathways. This approach significantly inhibits tumor growth, offering a promising new cancer treatment strategy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Ferroptosis is a promising cancer treatment, but its efficacy is limited by three main defense pathways: glutathione (GSH)-glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1)-ubiquinol (CoQH2), and dihydroorotate dehydrogenase (DHODH)-CoQH2.
  • Overcoming these defense mechanisms is crucial for effective ferroptosis-based cancer therapies.

Purpose of the Study:

  • To design a novel drug delivery system (SRF@Au@M NPs) based on MIL-100(Fe) that can predictably break the three ferroptosis defense systems in tumor cells.
  • To investigate the synergistic effects of sorafenib, gold nanoparticles, and a novel redox-CRN for enhanced ferroptosis induction.

Main Methods:

  • Fabrication of SRF@Au@M NPs via size optimization of MIL-100(Fe), sorafenib loading, in-situ gold nanoparticle growth, and surface modification.
  • Investigating the mechanism of SRF@Au@M NPs in releasing sorafenib, generating reactive oxygen species (ROS), and disrupting NAD(P)H metabolic homeostasis.
  • Evaluating the therapeutic efficacy of SRF@Au@M NPs in 4T1 tumor cells and tumor-bearing mice models.

Main Results:

  • SRF@Au@M NPs effectively released sorafenib, inhibited GPX4 activity, and disrupted carbohydrate metabolism.
  • A novel redox-CRN was established, continuously generating ROS and consuming NADH, leading to the inhibition of FSP1-CoQH2 and DHODH-CoQH2 pathways.
  • SRF@Au@M NPs induced a potent ferroptosis storm in 4T1 tumor cells, achieving 92.5% tumor growth inhibition in mice.

Conclusions:

  • The developed SRF@Au@M NPs successfully broke the three ferroptosis defense pathways by leveraging chemical reaction network principles.
  • This strategy provides a new paradigm for ferroptosis activation and demonstrates significant potential for cancer treatment.
  • The study highlights the importance of targeting multiple defense mechanisms for enhanced therapeutic outcomes in cancer therapy.
Keywords:
Cancer treatmentChemical reaction networksFenton reactionFerroptosisMetal-organic frameworks

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