A ratiometric fluorescent probe for imaging the fluctuation of HOBr during endoplasmic reticulum stress

Endoplasmic reticulum (ER) stress is closely associated with cell apoptosis, autophagy, DNA damage, metabolism, and migration. When ER stress occurs, a large number of reactive oxygen species, including hypobromous acid (HOBr), are generated. The degree of ER stress can be understood by accurately detecting the HOBr concentration in the ER. Unfortunately, no ER-targetable probes for detecting HOBr have been reported to date. To solve this problem, we developed a naphthalimide-based fluorescent probe (ER-NABr) for imaging HOBr in the ER. Upon reaction with HOBr, a red shift in the fluorescence spectrum occurs due to the difference in the molecular conjugation between the original ER-NABr and the reaction product. ER-NABr showed a fast response (within 30 s) and high selectivity towards HOBr, with a ratiometric quantitative response (5-40 μM) and high sensitivity (138 nM). With its excellent biocompatibility and remarkable ER-targetable ability, ER-NABr was successfully utilized to ratiometrically image intracellular HOBr, particularly during ER stress, which is beneficial for revealing the role of HOBr in ER-associated diseases.