A mitochondrial targeted near-infrared ratio fluorescent probe for ferroptosis related hydrogen polysulfides imaging in arthritis

Abstract

Hydrogen polysulfide (H₂S_n, n > 1), as an active sulfur substance derived from hydrogen sulfide, is considered a new potential signaling molecule that occupies an irreplaceable position in physiological regulation and signal transduction processes. Ferroptosis, an iron-dependent form of programmed cell death, is caused by the iron dependent accumulation of lipid peroxides associated with reactive oxygen species. The process of ferroptosis generates abundant reactive oxygen species, indirectly promoting the elevation of intracellular hydrogen polysulfide levels. There is evidence to suggest a close relationship between ferroptosis and arthritis. This work developed a near-infrared ratiometric fluorescent probe (Mito-S₄) with a large Stokes shift (∼240 nm) based on nucleophilic addition mechanism, which can quickly (18 s) and sensitively (Detection Limit = 0.165 μM) detect H₂S_n in cells. The mechanism of action was verified through theoretical calculations and nuclear magnetic analysis, and the probe Mito-S₄ was successfully applied to visualize H₂S_n in cellular mitochondria. The cell imaging results showed that the probe successfully achieved tracking of H₂S_n in mitochondria during inflammation and ferroptosis processes. In addition, pathological section experiments have confirmed that the probe has good in vivo imaging ability. It is worth mentioning that further in vivo imaging experiments have for the first time delved into the mechanism of H₂S_n in the process of ferroptosis in arthritis, which can provide new research methods and therapeutic targets for the treatment of arthritis.