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Triggered All-Active Metal Organic Framework: Ferroptosis Machinery Contributes to the Apoptotic Photodynamic

Xuan Meng1, Jian Deng1, Fang Liu1

  • 1School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin University , Tianjin 300072 , China.

Nano Letters
|October 10, 2019
PubMed

Insights

This study shows that a novel nanocarrier enhances photodynamic therapy (PDT) by depleting glutathione (GSH) and inducing ferroptosis, leading to effective tumor suppression in mice.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Photodynamic therapy (PDT) is a promising cancer treatment, primarily inducing apoptosis.
  • The role of ferroptosis in PDT and its manipulation via nanocarriers remain areas for exploration.

Purpose of the Study:

  • To investigate the potential of a redox-responsive nanocarrier to induce ferroptosis alongside PDT.
  • To validate the contribution of ferroptosis to the antitumor efficacy of nanoscale PDT.

Main Methods:

  • Fabrication of a disulfide-bearing metal-organic framework (MOF) nanocarrier encapsulating chlorin e6 (Ce6).
  • Assessment of intracellular glutathione (GSH) depletion, glutathione peroxide 4 (GPX4) inactivation, and cytotoxicity in 4T1 cells.
  • Evaluation of in vivo antitumor efficacy and ferroptosis inhibition in a 4T1 tumor-bearing mice model.

Main Results:

  • The Ce6-loaded MOF nanocarrier depleted intracellular GSH and induced ferroptosis, independent of light.
  • GSH depletion led to GPX4 inactivation and enhanced cytotoxicity, which was reversible with ferroptosis inhibitors.
  • The nanocarrier demonstrated significant in vivo antitumor efficacy, suppressed tumor growth, and improved survival rates in mice.

Conclusions:

  • The developed all-active MOF nanocarrier effectively induces ferroptosis, contributing significantly to antitumor PDT.
  • Targeting ferroptosis presents a viable strategy to enhance the efficacy of nanoscale photodynamic therapy.
Keywords:
Photodynamic therapydrug deliveryferroptosismetal organic frameworkredox-responsive

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