A water-soluble and lysosome-targeted pH fluorescent probe for analytical monitoring of cellular oxidative stress and in vivo non-invasive imaging of alcoholic gastritis in mice

Abstract

As a key acidic organelle, the pH homeostasis of lysosomes is critical for cellular functions. Existing pH fluorescent probes generally face limitations such as poor water solubility, insufficient targeting, and narrow pH response range, which hinder their practical applications in biomedical fields. In this study, a novel lysosome-targeted fluorescent probe, ANM, was designed and synthesized, which was molecularly optimized to possess excellent water solubility, precise lysosomal localization ability (P = 0.94), and a wide range of pH response properties (pH 3–8). ANM exhibits high fluorescence quantum yield (52.59%) and excellent photostability and selectivity for real-time monitoring of lysosomal pH dynamics in complex biological environments. ANM was demonstrated to be useful for visual imaging of lysosomal pH imbalance under oxidative stress and it enabled non-invasive diagnosis of gastritis in a mouse model of alcoholic gastritis by means of oral administration. This work provides a new strategy for developing diagnostic tools for pH imbalance-related diseases.