A two-photon endoplasmic reticulum-targeting fluorescent probe for the imaging of pH in living cells and zebrafish

Abstract

The pH changes of the endoplasmic reticulum (ER) are closely related to many diseases. Herein, we present a new pH-sensitive fluorescent probe (Na-pH) for the observation of ER acidification in living cells and ER stress in vivo. Na-pH consists of 1,8-naphthalimide as a fluorescence-on signal unit, 4-methylbenzenesulfonamide moiety for ER localization, and piperazine group as a pH-responsive site. Na-pH shows a sensitive fluorescence enhancement under acidic conditions, allowing it to monitor ER acidification. Meanwhile, Na-pH has a negligible response to common species, and possesses low cytotoxicity. In biological experiments, Na-pH can be used for tracking acidification during ER stress. In addition, Na-pH was also applied for two-photon imaging of pH in living tissues and zebrafish. We expect that Na-pH has great potential as a practical tool for real-time monitoring of ER acidification, which helps to reveal the pathogenesis of ER stress-related diseases.