A Mitochondria-Targeting Probe for Extended Imaging of H ₂ S and Viscosity in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a destructive autoimmune disease that is closely related to hydrogen sulfide (H 2 S) and intracellular viscosity. This study highlights the dual characteristics of H 2 S as an anti-inflammatory signaling molecule and the influence of intracellular viscosity on cellular signaling. Therefore, a dual-responsive probe ( MS-L ) was developed to simultaneously monitor H 2 S and viscosity. In addition to obtaining quantifiable emission from 606 to 598 nm upon MS-L reacting with H 2 S, the intramolecular charge transfer sensing mechanism was achieved, following which MS-OH was produced. The predicted mechanism was then confirmed by 1 H NMR, HR-MS, HPLC, and DFT. The emission of the probe was enhanced in high-viscosity liquids, which inhibit twisted intramolecular charge transfer and prevent energy loss via nonradiative decay. Remarkably, MS-L could selectively image mitochondrial H 2 S and viscosity in addition to long-time visualizing. The probe could distinguish healthy cells from cancerous cells by measuring endogenous H 2 S levels and viscosity. Studies on a mouse model of RA induced by λ-carrageenan reveal that MS-L offers excellent real-time and long-term imaging capabilities for RA. Moreover, with MS-L, substantial increases in joint tissue H 2 S and viscosity were observed during RA. All findings suggest that MS-L is a highly effective tool for the examination and diagnosis of RA.