Improving 5-Aminolevulinic acid photodynamic therapy through the modulation of iron metabolism

IF 2.6 3区医学 Q2 ONCOLOGY

Photodiagnosis and Photodynamic Therapy Pub Date : 2025-08-10 DOI:10.1016/j.pdpdt.2025.104755

Chenhan Li, Shun-ichiro Ogura

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引用次数: 0

Abstract

Background

5-aminolevulinic acid-based photodynamic therapy (ALA–PDT) has emerged as a promising cancer treatment owing to its selectivity and minimal invasiveness. However, certain cancer types exhibit resistance to ALA–PDT, partly due to insufficient protoporphyrin Ⅸ (PpⅨ) accumulation. This study aimed to enhance PpⅨ accumulation by modulating iron metabolism.

Methods

Two cancer cell lines were used in this study, TMK-1 and MCF-7. Divalent metal transporter 1 (DMT1) was knocked down genetically, and the iron chelator deferoxamine (DFO) was used to downregulate ferrochelatase (FECH). The cellular levels of PpⅨ, reactive oxygen species, Fe²⁺, and cell viability were determined to evaluate the efficacy of ALA–PDT.

Results

Knocking down DMT1 increased PpⅨ accumulation in TMK-1 cells but did not contribute to it in MCF-7 cells. DFO enhanced PpⅨ accumulation in both cell lines, primarily by removing excess iron ions and inhibiting FECH.

Conclusion

This study offers a novel strategy for improving the efficacy of ALA–PDT through the modulation of iron metabolism, achieved by targeting DMT1 and utilizing the iron chelator DFO. Additionally, DFO exhibited a dual mechanism, depending on cellular iron homeostasis.

查看原文本刊更多论文

通过调节铁代谢改善5-氨基乙酰丙酸光动力疗法。

背景：基于5-氨基乙酰丙酸的光动力疗法（ALA-PDT）因其选择性和微创性而成为一种很有前途的癌症治疗方法。然而，某些类型的癌症表现出对ALA-PDT的耐药性，部分原因是原卟啉Ⅸ（PpⅨ）积累不足。本研究旨在通过调节铁代谢促进PpⅨ积累。方法：采用TMK-1和MCF-7两种癌细胞系进行实验。基因敲除二价金属转运蛋白1 (DMT1)，并利用铁螯合剂去铁胺（DFO）下调铁螯合酶（FECH）。通过测定细胞中PpⅨ、活性氧、Fe2+水平和细胞活力来评价ALA-PDT的疗效。结果：敲除DMT1可增加TMK-1细胞中PpⅨ的积累，但对MCF-7细胞没有影响。DFO主要通过去除多余的铁离子和抑制FECH来增强两种细胞系中PpⅨ的积累。结论：本研究通过靶向DMT1，利用铁螯合剂DFO，提供了一种通过调节铁代谢来提高ALA-PDT疗效的新策略。此外，DFO表现出双重机制，依赖于细胞铁稳态。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Photodiagnosis and Photodynamic Therapy ONCOLOGY-

CiteScore

5.80

自引率

24.20%

发文量

509

审稿时长

50 days

期刊介绍： Photodiagnosis and Photodynamic Therapy is an international journal for the dissemination of scientific knowledge and clinical developments of Photodiagnosis and Photodynamic Therapy in all medical specialties. The journal publishes original articles, review articles, case presentations, "how-to-do-it" articles, Letters to the Editor, short communications and relevant images with short descriptions. All submitted material is subject to a strict peer-review process.