A Fast-Responsive OFF–ON Near-Infrared-II Fluorescent Probe for In Vivo Detection of Hypochlorous Acid in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease, and its etiology is closely related to the overproduction of hypochlorous acid (HClO). However, early detection of RA using an activatable near-infrared-II (NIR-II, 1000-1700 nm) fluorescent probe remains challenging. Herein, we first report an "OFF-ON" NIR-II fluorescent probe named PTA (phenothiazine triphenylamine) for imaging HClO in deep-seated early RA. Electron-rich phenothiazine in the core of PTA was utilized as both an HClO-recognition moiety and a precursor of electron acceptors, displaying a typical donor-acceptor-donor structure with excellent NIR-II emission at 936/1237 nm once reacted with HClO. The probe PTA exhibited good water solubility, high photostability, and rapid response capability toward HClO within 30 s. Moreover, it was able to sensitively and specifically detect exogenous and endogenous HClO in living cells in both visible and NIR-II windows. Notably, PTA enabled the sensitive and rapid visualization of HClO generation in an inflammatory RA mouse model, showing a 4.3-fold higher NIR-II fluorescence intensity than that in normal hindlimb joints. These results demonstrate that PTA holds great promise as a robust platform for diagnosis of HOCl-mediated inflammatory disorders.