GSH and H2O2 dynamic correlation in the ferroptosis pathways revealed by engineered probe in tumor and kidney injury

Abstract

Ferroptosis is a cell death mode of lipid peroxidation caused by iron metabolism disorder and redox imbalance, which is closely associated with the evolution of tumour and ischemia reperfusion injury and other diseases, and it involves the excessive accumulation of reactive oxygen species promoting ferroptosis pathway and thiols-associated anti-ferroptosis pathway. To study the dynamic correlation between reactive oxygen species and active sulfur in the two pathways is of great significance for revealing the precise regulation mechanism of ferroptosis. Hydrogen peroxide (H2O2) and glutathione (GSH), as very active redox species in organisms, participate dynamically in the ferroptosis process. In this study, hemicyanine dye conjugated H2O2 specific response site were coupled with coumarin derivative containing GSH specific response site, realizing distinguishing simultaneous detection of H2O2 and GSH through near-infrared and cyan fluorescence emission after response. At the cellular level, the dynamic correlation between H2O2 and GSH in the ferroptosis pathway was explored, and the synergistic ferroptosis inducer was screened for further application at the tumor level, then monitoring the process of ferroptosis inducer used for tumor ablation and ferroptosis inhibitor used to alleviate kidney ischemia–reperfusion injury by fluorescence imaging.