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TRPV-1-targeted Fe-phenolate network provokes apoptosis and ferroptosis to treat non-small cell lung cancer

Ziyi Wang1,2, Liang Shao2, Chunbao Wang1

  • 1Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn.

Biomaterials Science
|July 7, 2026
PubMed

Insights

This study introduces a novel ferroptosis-inducing therapy for non-small cell lung cancer (NSCLC). The approach targets TRPV1 channels, simultaneously triggering apoptosis and ferroptosis for enhanced cancer cell killing.

Area of Science:

  • Biochemistry
  • Oncology
  • Nanotechnology

Background:

  • Ferroptosis is a promising cancer therapy target.
  • Non-small cell lung cancer (NSCLC) shows resistance to ferroptosis.
  • Targeting TRPV1 channels offers a new strategy for NSCLC treatment.

Purpose of the Study:

  • To develop a dual-action therapeutic platform for NSCLC.
  • To enhance NSCLC vulnerability to cell death induction.
  • To investigate a TRPV1-targeting approach for simultaneous apoptosis and ferroptosis.

Main Methods:

  • A novel platform delivering iron and a TRPV1 agonist (N-oleoyldopamine, OLDA) was developed.
  • The platform was designed to target cancer cells and induce intracellular iron and OLDA release.
  • Cellular responses (apoptosis, ferroptosis) and in vivo efficacy were evaluated.

Main Results:

  • The FeOLDA platform selectively killed A549 NSCLC cells compared to normal cells.
  • Intracellular OLDA activated TRPV1, leading to Ca2+ overload, mitochondrial/ER stress, and apoptosis.
  • Iron ions induced ferroptosis by depleting GPX4/GSH and increasing lipid peroxides.
  • FeOLDA suppressed tumor growth in vivo without causing systemic toxicity.

Conclusions:

  • The FeOLDA platform effectively induces simultaneous apoptosis and ferroptosis in NSCLC.
  • This dual-action strategy overcomes inherent ferroptosis resistance in NSCLC.
  • FeOLDA represents a targeted and efficient therapeutic approach for lung cancer treatment.

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