Work

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

Year: 2025

Type: article

Abstract: • The efficacy of ALA–PDT is closely linked to iron metabolism. • Divalent metal transporter 1 represents a promising target for improving ALA–PDT. • Deferoxamine improves ALA–PDT through dual mechanisms, depending on cellular iron homeostasis. 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. 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, Fe 2+ , and cell viability were determined to evaluate the efficacy of ALA–PDT. 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. 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.

Source: Photodiagnosis and Photodynamic Therapy

DOI: 10.1016/j.pdpdt.2025.104755

Authors: Chenhan Li, Shun-ichiro Ogura

Institution: Institute of Science Tokyo

Language: English

Topic: Photodynamic Therapy Research Studies

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,610