Rapid Response Fluorescence Probe Enabled In Vivo Diagnosis and Assessing Treatment Response of Hypochlorous Acid‐Mediated Rheumatoid Arthritis

Abstract

Abstract Diagnosis and early assessment of the treatment response of rheumatoid arthritis (RA) necessitates a reliable bioanalytical method for rapid, sensitive, and specific detection of the hypochlorous acid (HOCl) biomarker in inflammatory diseases. Herein, two fluorescence probes, Probe‐ 1 and Probe‐ 2 are developed for quantitative monitoring and visualization of inflammatory response–related HOCl levels in vitro and in vivo. In the presence of HOCl, fluorescence “OFF–ON” response is obtained for both the probes as a result of specific HOCl‐triggered CN bond cleavage reaction. Probe‐ 1 and Probe‐ 2 feature rapid response (<4 s), a high degree of sensitivity and selectivity toward HOCl, which allow them to be used for quantification of HOCl in a simulated physiological condition. Using Probe‐ 2 as the probe, fluorescence imaging and flow cytometry analysis of HOCl levels in lysosome of inflammatory mimic cells, visualization of HOCl generation in endotoxin‐induced inflammation of adult zebrafish and RA of mice are possible. Probe‐ 2 exhibits high effectiveness for early assessment of the treatment response of HOCl‐mediated RA in mice with an antiarthritic drug, methotrexate (MTX). The results demonstrate that Probe‐ 2 is a powerful tool for future studies on diagnosis and monitoring treatment efficiency in a broad range of inflammatory diseases, including RA.