Ultra-pH-sensitive sensor for visualization of lysosomal autophagy, drug-induced pH alteration and malignant tumors microenvironment

Abstract The acidity of lysosome is essential to complete its own physiological activities. The abnormal fluctuation of pH in lysosome can cause many serious diseases, such as cancer and Alzheimer's disease. Therefore, it is particularly important to develop a tool for visualizing detection the pH fluctuations of lysosome. Herein, a new ratiometric fluorescent probe (SN-Lyso) with (ICT-FRET) dual mechanism for detecting pH fluctuations of lysosomes was proposed, which was the combination of the 2-(2-morpholinoethyl)-1,8-naphthalic anhydride and spiropyran by a nonconjugated linker. SN-Lyso responded to acid and alkali pH changes with red and green emissions, respectively. Meanwhile, SN-Lyso was successfully applied in fluorescence imaging in living cells. It was found that cells undergoing autophagy could cause lysosomal pH to decrease, and chloroquine-stimulated result in lysosomal pH to increase. In addition, SN-Lyso was sensitive to pH and could specifically identify tumor in mice. We expect that SN-Lyso will provide an efficient method for studying the mechanism of lysosomal pathology and visualizing the treatment of tumor sites.