A near-infrared ratiometric fluorescent probe for ferroptosis related hydrogen polysulfides imaging in arthritis

Hydrogen polysulfide (H₂S_n, n > 1) is considered a highly promising new signaling molecule that plays an irreplaceable key role in physiological regulation. Ferroptosis is primarily driven by iron-dependent accumulation of lipid peroxides related to reactive oxygen species under the action of iron. During the process of ferroptosis, large amounts of ROS are produced, which promote an increase in intracellular levels of hydrogen polysulfide. There are studies indicating a close and undeniable association between ferroptosis and arthritis. Based on this, our study synthesized a near-infrared ratiometric fluorescent probe TMN-S₄ for in vivo and in vitro detection and imaging of H₂S_n. TMN-S₄ exhibits high sensitivity (DL = 0.38 μM) and selectivity towards H₂S_n, and cytotoxicity assays have shown that it has low biological toxicity and good biocompatibility. The nucleophilic substitution mechanism between the probe and H₂S_n was verified through spectroscopic experiments and NMR analysis, and the probe TMN-S₄ has been effectively used for track and image endogenous and exogenous H₂S_n sources in cells. In addition, the probe monitored the changes in intracellular H₂S_n expression levels during ferroptosis in a ratio signal mode. More importantly, TMN-S₄ successfully achieved imaging of H₂S_n in arthritis mice associated with ferroptosis. This provides an effective experimental tool for a deeper understanding of the mechanism of action of H₂S_n in arthritis caused by ferroptosis.