Imaging of intracellular sulfane sulfur expression changes under hypoxic stress via a selenium-containing near-infrared fluorescent probe

Hypoxia is a significant global issue affecting the health of organisms. Oxygen homeostasis is critical for mammalian cell survival and cellular activities. Hypoxic stress can lead to cell injury and death, which contributes to many diseases. Sulfane sulfur is involved in crucial roles in physiological processes of maintaining intracellular redox state and ameliorating oxidative damage. Therefore, real-time imaging of changes in sulfane sulfur levels is important for understanding their biofunctions in cells. In this study, we develop a new near-infrared (NIR) fluorescent probe BD-diSeH for imaging of sulfane sulfur changes in cells and in vivo under hypoxic stress. The probe includes two moieties: an NIR azo-BODIPY fluorophore equipped with a strong nucleophilic phenylselenol group (–SeH). The probe is capable of tracing dynamic changes of endogenous sulfane sulfur based on a fast and spontaneous intramolecular cyclization reaction. The probe has been successfully used for imaging sulfane sulfur in 3D-multicellular spheroid and mouse hippocampus under hypoxic stress. The overall levels of sulfane sulfur are affected by the degree and length of hypoxic stress. The results reveal a close relationship between sulfane sulfur and hypoxia in living cells and in vivo, allowing better understanding of physiological and pathological processes involving sulfane sulfur. Moreover, to investigate the effects of environmental hypoxia on aquatic animals, this probe has been applied for sulfane sulfur detection in hypoxic zebrafish.