Biological and Medicinal Chemistry

A Visible Light-triggered Ferroptosis Probe: Visualization, Endoplasmic Reticulum Localization and Photo-induced Lipid Peroxidation

Authors

  • Zhibin Song College of Chemistry and Chemical Engineering & Jiangxi Normal University ,
  • Zhiming Xing College of Chemistry and Chemical Engineering & Jiangxi Normal University ,
  • Jiangyu Yan Institute of Chemical Biology and Nanomedicine & Hunan University ,
  • Yongxiang Miao College of Chemistry and Chemical Engineering & Jiangxi Normal University ,
  • Yawen Ruan Institute of Chemical Biology and Nanomedicine & Hunan University ,
  • Youkang Zhou College of Chemistry and Chemical Engineering & Jiangxi Normal University ,
  • Yingqun Tang College of Chemistry and Chemical Engineering & Jiangxi Normal University ,
  • Guorui Li Institute of Chemical Biology and Nanomedicine & Hunan University ,
  • Jing Huang Institute of Chemical Biology and Nanomedicine & Hunan University ,
  • Yiyuan Peng College of Chemistry and Chemical Engineering & Jiangxi Normal University

Abstract

Accumulation of lethal lipid peroxidation plays the central role in ferroptosis initiation and execution. However, it remains unclear whether the location of lipid peroxidation accumulation in subcellular organelles contributes to ferroptosis initiation due to the lack of specific small-molecule probe. Here we report a quinazolinone-pyridine difluoroboron complex (BODIQPys) with vinyltriphenylamine modification, BODIQPy-TPA, as a near-infrared (NIR) bioimaging and photo-induced ferroptosis bifunctional probe. BODIQPy-TPA with D-π-A structure exhibits a good endoplasmic reticulum (ER) localization and photo-activated lipid reactive oxygen species (ROS) generation. The photo-induced ferroptosis is confirmed by morphological changes of live cell fluorescence imaging, suppression of cell death by a ferroptosis inhibitor (Fer-1) and down-regulation of ferritin heavy polypeptide 1 (FTH1). This study is the first example of visual photo-induced ferroptosis by small organic molecular probe, which provides a promising tool for further investigation of the direct relationship between lipid peroxidation accumulation and ferroptosis. Moreover, ferroptosis induced by photodynamic therapy (PDT) process in ER will be a good strategy to improve the efficiency of PDT for apoptosis-resistant tumor cells.

Content

Thumbnail image of Manuscript for ChemRxiv.pdf

Supplementary material

Thumbnail image of Supporting information.pdf
Supporting Information
Experimental details and crystal, magnetic property data and analytical data for all compounds
Thumbnail image of movie 1.pptx
Movie of photo-induced ferroptosis in B16 Cells
The morphology of the cells changes with continuous light irradiation in the process of photo-induced ferroptosis.