Design and application of lysosomal targeting pH-sensitive ?-galactosidase fluorescent probe

beta-galactosidase is a lysosomal enzyme that plays an essential biological function as a cancer marker in many physiological and pathological processes. Therefore, it is of great significance to study the detection and visualization methods of its activity in organelles. Here, we propose a feasible design strategy to switch fluorescence using an intramolecular photoinduced electron transfer (PET) process to obtain a pH-sensitive beta-gal activable fluorescent probe (MLC). The probe was able to react selectively with beta-gal and produce a strong fluorescence signal at low pH (4.5-6). Because of its special pH response mode, the probe has a similar function of double lock, with demonstrates high selectivity toward beta-gal, lower cytotoxicity, lysosomal localization, and fast response time (<10 min). In addition, with the help of MLC, we successfully visualized beta-gal in ovarian cancer cells at different pH conditions. Notably, no beta-gal fluorescent probe design using this strategy has yet been developed. We hope that these applications will make MLC a potentially powerful tool in the prevention and treatment of cancer.

Automated summary

In this study, a feasible design strategy using intramolecular photoinduced electron transfer (PET) process was proposed to obtain a pH-sensitive beta-gal activable fluorescent probe (MLC). The probe selectively reacted with beta-gal and produced strong fluorescence at low pH. The probe demonstrated high selectivity, lower cytotoxicity, lysosomal localization, and fast response time, making it a potentially powerful tool in cancer prevention and treatment.