ACS Sens. 2020, 5,7,1949-1958.

Ji-Ting Hou, Bingya Wang, Yuxia Zou, Peiwen Fan, Xueping Chang, Xinhua Cao*, Shan Wang*, and Fabiao Yu*

The early diagnosis of osteoarthritis (OA) can halt or delay the progression of the disease, and it is essentially beneficial to its treatment. However, biomarkers with sufficient sensitivity for dynamically identifying early OA are still yet to be determined. The overproduced hypochlorous acid (HOCl) has been proposed as an obvious symptom in early OA. Herein, based on the oxidation reaction of the sulfur atom in phenothiazine into sulfoxide, we design and synthesize a phenothiazine-derived coumarin fluorescent probe PDC for the detection of ClO in cells and in an OA mouse model. The probe PDC exhibits excellent selectivity and sensitivity for ClO detection with a limit of detection as low as 16.1 nM. Taking advantage of the probe PDC, we visualize and evaluate the level changes of ClO in macrophage cells, which is stimulated by various inflammatory factors. The anti-inflammatory and therapeutic effects of selenocysteine and methotrexate in inflamed cells are also confirmed. Finally, with in vivo imaging of ClO concentration changes in OA BALB/c mouse models, we successfully inspected the relationship between OA phenotypes and the burst of ClO. We suggest that abnormal changes in HOCl concentration may be considered as a new biomarker for the early OA diagnosis.