---
title: "TRPV1-targeted Fe-phenolate (FeOLDA) induces apoptosis and ferroptosis in NSCLC"
id: "pubmed-42411334"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42411334"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42411334/"
doi: "10.1039/d6bm00434b"
published_at: "2026-08-11T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# TRPV1-targeted Fe-phenolate (FeOLDA) induces apoptosis and ferroptosis in NSCLC
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42411334
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42411334/)
- **DOI:** [10.1039/d6bm00434b](https://doi.org/10.1039%2Fd6bm00434b)
- **Published At:** 2026-08-11T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study describes a **TRPV1-targeted Fe-phenolate network** (FeOLDA) that self-delivers intracellular iron (Fe3+) and the TRPV1 agonist N-oleoyldopamine (OLDA) to non-small cell lung cancer (**NSCLC**) cells. - OLDA released intracellularly activates **TRPV1** channels, producing Ca2+ overload and provoking mitochondrial and endoplasmic reticulum stress that leads to **apoptosis**. - Released Fe3+ ions catalyze Fenton reactions that deplete antioxidant defenses (GPX4/GSH) and increase lipid peroxides, triggering **ferroptosis**. - FeOLDA showed selective cytotoxicity for A549 NSCLC cells compared with normal bronchial epithelial BEAS-2B cells in vitro. - In vivo, FeOLDA suppressed tumor growth while avoiding weight loss and multi-organ toxicity observed with cisplatin in the reported experiments. - The platform is presented as a dual-action, lung cancer–targeted strategy to overcome NSCLC resistance to ferroptosis by combining apoptosis and ferroptosis induction. - Specific experimental details, dosing regimens, quantitative efficacy metrics, and full safety data were not reported in the provided source abstract.
## Clinical Analysis & Structured Key Points
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R. China. zhangjiaxjtu@xjtu.edu.cn.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-2 "Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn."), [Liang Shao](https://pubmed.ncbi.nlm.nih.gov/?term=Shao+L&cauthor_id=42411334)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-2 "Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn."), [Chunbao Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+C&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Dawei Luo](https://pubmed.ncbi.nlm.nih.gov/?term=Luo+D&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Lu Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+L&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Rong Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+R&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Ting Liang](https://pubmed.ncbi.nlm.nih.gov/?term=Liang+T&cauthor_id=42411334)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-3 "Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China."), [Guanying Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+G&cauthor_id=42411334)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-2 "Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn."), [Jia Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+J&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#full-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn.") Affiliations Expand ### Affiliations * 1 Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn. * 2 Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn. * 3 Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. * PMID: **42411334** * DOI: [ 10.1039/d6bm00434b ](https://doi.org/10.1039/d6bm00434b) Item in Clipboard # TRPV-1-targeted Fe-phenolate network provokes apoptosis and ferroptosis to treat non-small cell lung cancer Ziyi Wang et al. Biomater Sci. 2026. Show details Display options Display options Format Abstract PubMed PMID Biomater Sci Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biomater+Sci%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biomater+Sci%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42411334/) . 2026 Aug 11;14(16):4336-4348. doi: 10.1039/d6bm00434b. ### Authors [Ziyi Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Z&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-2 "Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn."), [Liang Shao](https://pubmed.ncbi.nlm.nih.gov/?term=Shao+L&cauthor_id=42411334)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-2 "Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn."), [Chunbao Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+C&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Dawei Luo](https://pubmed.ncbi.nlm.nih.gov/?term=Luo+D&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Lu Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+L&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Rong Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+R&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn."), [Ting Liang](https://pubmed.ncbi.nlm.nih.gov/?term=Liang+T&cauthor_id=42411334)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-3 "Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China."), [Guanying Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+G&cauthor_id=42411334)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-2 "Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn."), [Jia Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+J&cauthor_id=42411334)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42411334/#short-view-affiliation-1 "Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn.") ### Affiliations * 1 Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. zhangjiaxjtu@xjtu.edu.cn. * 2 Department of Biophysics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. guanyingli@xjtu.edu.cn. * 3 Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, P. R. China. * PMID: **42411334** * DOI: [ 10.1039/d6bm00434b ](https://doi.org/10.1039/d6bm00434b) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Ferroptosis has emerged as a potential therapeutic target for chemotherapy of cancer. However, non-small cell lung cancer (NSCLC) exhibits high tolerance to ferroptosis due to inherent resistance. To increase NSCLC vulnerability, we present a TRPV1-targeting approach that self-delivers intracellular irons and TRPV1 agonist (_N_ -oleoyldopamine, OLDA) to provoke simultaneous apoptosis and ferroptosis in NSCLC. Intracellular release of OLDA activates TRPV1 channels, triggering Ca2+ overload and mitochondrial/ER stress to induce apoptosis, while Fe3+ ions drive Fenton reactions, depleting GPX4/GSH and elevating lipid peroxides to induce ferroptosis. FeOLDA demonstrated selective cytotoxicity toward A549 NSCLC cells over normal bronchial epithelial BEAS-2B cells. _In vivo_ studies demonstrate that FeOLDA effectively suppresses tumor growth without weight loss or multi-organ toxicity associated with cisplatin. This dual-action platform offers a lung cancer-targeted and efficient strategy for NSCLC treatment. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Quercetagitrin targets EIF3D to activate NCOA4-mediated ferritinophagy-dependent ferroptosis for the treatment of non-small cell lung cancer. ](https://pubmed.ncbi.nlm.nih.gov/41653617/) Tang X, Wu F, Rao H, Luo X, Zhang G, Lai X, Li C, Fang J, Li H.Tang X, et al.Phytomedicine. 2026 Apr;153:157914. doi: 10.1016/j.phymed.2026.157914. Epub 2026 Feb 2.Phytomedicine. 2026.PMID: 41653617 * [ Gallic acid: A promising anti-non-small cell lung cancer compound targeting early growth response protein-1 for apoptosis and ferroptosis. ](https://pubmed.ncbi.nlm.nih.gov/42030802/) Li BB, Zhang JT, Jiang YY, Li X, Wang DN, Zang JM, Liu ZL, Hu FX, Zhu X, Shen CC, Zhang W, Xu F.Li BB, et al.Phytomedicine. 2026 Jul;156:158220. doi: 10.1016/j.phymed.2026.158220. 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