Hypochlorous acid-activatable two-photon excited NIR fluorescent probe with a high signal-to-background ratio for imaging osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease, and early diagnosis of OA is crucial for its treatment, which is more beneficial for osteoarthritis patients to relieve symptoms, delay disease progression, and improve quality of life. Hypochlorous acid plays a "double-edged sword" role in OA, and can serve as a biomarker for OA. Here, based on the advantages of NIR fluorescent probe and two-photon fluorescent probe, a hypochlorous acid-activatable two-photon excited NIR fluorescent probe (TP-NIR-HClO) based on spirolactam ring-opening strategy was developed for imaging OA this paper. TP-NIR-HClO showed a highly selective two-photon excited NIR fluorescence "off-on" response for HClO in solution, with a high signal-to-background ratio (the maximum SBR was approximately 150), a detection limit (30 nM), and a linear response range (150 nM to 6 μM). Moreover, TP-NIR-HClO was successfully applied for two-photon imaging of HClO in cells and tissues, with a maximum imaging depth of 225 μM. Finally, TP-NIR-HClO was successfully applied for imaging osteoarthritis in mice. All the results confirm that TP-NIR-HClO is a useful tool for imaging HClO in biosystem and studying the pathology and the diagnosis of osteoarthritis.