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Updated: Jun 7, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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A positive-feedback loop suppresses TNBC tumour growth by remodeling tumour immune microenvironment and inducing

Pingting Ye1, Chunhui Wang1, Yixuan Wen1

  • 1Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200120, China.

Biomaterials
|November 14, 2024
PubMed

Insights

This study developed novel nanoparticles loaded with metformin to induce ferroptosis, a cell death mechanism. This approach enhances the immune response against triple-negative breast cancer (TNBC), offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Immunotherapy
  • Nanomedicine
  • Biomedical Engineering

Background:

  • Triple-negative breast cancer (TNBC) is aggressive, characterized by poor immunogenicity and limited immune cell infiltration, necessitating advanced therapeutic strategies.
  • Ferroptosis, a form of programmed cell death, can enhance tumor immunogenicity and activate the immune system, making it a promising avenue for cancer treatment.
  • Metformin (MET), an anti-diabetic drug, can modulate the tumor immune microenvironment (TIME) and foster an immunostimulatory environment.

Purpose of the Study:

  • To investigate the potential of metformin to promote ferroptosis and enhance the immune response in TNBC.
  • To design and develop a novel nanoparticle system for targeted delivery of metformin to induce ferroptosis and remodel the TIME.

Main Methods:

  • Development of self-assembled metformin-loaded Fe3+-doped polydopamine nanoparticles (Fe-PDA-MET NPs).
  • Induction of ferroptosis in TNBC cells using Fe-PDA-MET NPs under 808 nm irradiation.
  • Evaluation of immune cell infiltration (CD8+ T cells and NK cells) and assessment of the ferroptotic positive-feedback loop.

Main Results:

  • Fe-PDA-MET NPs effectively disordered cellular redox homeostasis and induced robust ferroptosis.
  • Metformin upregulated intracellular l-Glutamine, promoting ferroptosis and remodeling the TIME.
  • Significant increase in CD8+ T cell and NK cell infiltration was observed, augmenting ferroptosis and enhancing the anti-tumor immune response.

Conclusions:

  • Fe-PDA-MET NPs establish a ferroptotic positive-feedback loop, offering an effective strategy for controlling TNBC progression.
  • This approach shows promise in enhancing tumor immunogenicity and reshaping the TIME for improved cancer immunotherapy.
Keywords:
FerroptosisMetforminNanoparticleT cell exhaustionThe tumour immune microenvironment

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