A two-photon fluorescent probe for turn-on monitoring HOCl level in endoplasmic reticulum

To understand the relationship between endoplasmic reticulum (ER) stress and the level of hypochlorous acid (HOCl), it is highly desired to develop an ER-targetable HOCl probe to monitoring the HOCl level. In this study, a new turn-on type of two-photon ER-targetable fluorescent probe (ER-NPA) is designed for fluorescent sensing and imaging HOCl in ER using 4-hydroxy-1,8-naphthalimide as the fluorophore , p-aminophenyl ether as the recognition receptor, and methyl sulfonamide as ER-targetable group. The probe ER-NPA exhibits some intrinsic features such as excellent water solubility, good biocompatibility , significantly fast and enhanced fluorescence response to HOCl within 60 s, and detection limit as low as 6.2 nM for HOCl determination. The probe ER-NPA is successfully applied to real-time monitoring of exogenous and endogenous HOCl fluctuations in HeLa cells and zebrafish during ER stress. The developed probe ER-NPA may provide a new strategy to reveal the chemical biology roles of HOCl in ER stress-related diseases.