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Metabolic Intervention Nanoparticles for Triple-Negative Breast Cancer Therapy via Overcoming FSP1-Mediated

Jie Yang1, Zengguang Jia1, Jun Zhang1

  • 1School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

Advanced Healthcare Materials
|April 8, 2022
PubMed

Insights

This study introduces Cu-SF(RSV) nanoparticles to combat triple-negative breast cancer (TNBC) by overcoming ferroptosis resistance. These nanoparticles target abnormal tumor metabolism, offering a new therapeutic strategy for TNBC.

Area of Science:

  • Biomedical engineering
  • Cancer research
  • Nanotechnology

Background:

  • Triple-negative breast cancer (TNBC) presents a poor prognosis due to its aggressive nature.
  • Ferroptosis, a regulated cell death, shows promise for TNBC treatment but faces resistance.
  • FSP1-mediated ubiquinone metabolism contributes to ferroptosis resistance in TNBC.

Purpose of the Study:

  • To develop Cu-SF(RSV) nanoparticles for inhibiting TNBC by overcoming FSP1-mediated ferroptosis resistance.
  • To investigate the mechanism of rosuvastatin (RSV) in disrupting redox homeostasis and ferroptosis resistance.
  • To evaluate the potential of these nanoparticles as a therapeutic platform for TNBC.

Main Methods:

  • Encapsulation of rosuvastatin (RSV) into silk fibroin (SF) nanoparticles (Cu-SF(RSV) NPs).
  • Intervention in the mevalonate pathway by RSV to disrupt the CoQ/FSP1 axis.
  • Generation of reactive oxygen species and glutathione depletion by Cu-SF(RSV) NPs to induce ferroptosis.

Main Results:

  • Cu-SF(RSV) NPs effectively overcome FSP1-mediated ferroptosis resistance in TNBC.
  • RSV disrupts metabolic pathways, restoring ferroptosis sensitivity.
  • The nanoparticles enhance ferroptosis by increasing oxidative stress.

Conclusions:

  • Cu-SF(RSV) nanoparticles represent a promising strategy for TNBC treatment.
  • Targeting tumor metabolism and ferroptosis resistance is a viable therapeutic approach.
  • Metabolic intervention nanoparticles offer a novel platform for clinical TNBC therapy.
Keywords:
ferroptosis resistancemetabolic interventionmetastasisstatins-loaded silk fibroin nanoparticlestriple-negative breast cancer

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