Near-Infrared Fluorescent Probe for Ratiometric Tracking Endogenous and Exogenous Lysosomal Hypochlorous Acid

Hypochlorous acid (HOCl) serves as a vital molecule in innate immune defense, and fluctuations of lysosomal HOCl levels may be linked to a range of physiological and pathological processes, which make the quantitative detection of lysosomal HOCl a necessity. Herein, we report the design and synthesis of a novel fluorescent probe, PD-OCl, which is constructed by conjugating phenothiazine and dicyanoisophorone moieties and exhibits near-infrared (NIR) emission and large Stokes shifts. Notably, PD-OCl can function as a robust ratiometric fluorescent probe for HOCl detection, exhibiting exceptional selectivity, high sensitivity, and rapid response kinetics. Additionally, the PD-OCl has been successfully applied for monitoring both exogenous and endogenous HOCl in living cells, where it displays excellent lysosomal targeting capability, providing a visualized and ratiometric approach for tracing the variations of subcellular HOCl levels. This work establishes PD-OCl as a promising candidate for investigating lysosomal HOCl levels in LPS-induced oxidative stress state cells.