An acid-enhanced OFF-ON fluorescent probe for the detection of hypochlorous acid in rheumatoid arthritis

Excessive production of hypochlorite acid (HClO) and lactic acid are general hallmarks in the microenvironment of rheumatoid arthritis (RA). Here, we, for the first time, report an acid-enhanced "OFF-ON" fluorescent probe PPS for the detection of HClO in vivo. The probe PPS showed good water solubility, large Stokes shift (143 nm), and fast response toward HClO within 100 s. In the presence of HClO, the sulfur atom in the core of phenothiazine would be oxidized into sulfoxide, triggering intense fluorescence at 580 nm, whose fluorescence intensity could be further enhanced under acidic conditions. Moreover, the exogenous and endogenous HClO in living cells could be sensitively and selectively detected by PPS with a low LOD of 24 nM. Notably, PPS was able to rapidly visualize endogenous HClO generation in a RA mouse model, exhibiting a 2.3-fold higher fluorescence intensity than it in normal joint and 4.1-fold enhanced fluorescence intensity at acidic pH.