Mapping dynamic changes in lysosomal polarity with a sensitive and large stokes shift fluorescent probe

Lysosomal polarity is closely associated with its functional integrity, and its dynamic changes serve as a key indicator for assessing cellular status and the progression of various diseases. However, currently available fluorescent probes for monitoring lysosomal polarity generally suffer from small Stokes shifts and insufficient sensitivity, leading to low signal-to-noise ratios and susceptibility to auto-fluorescence interference, making it difficult to accurately track dynamic fluctuations. To address the above challenge, this study successfully developed a novel lysosome-targeted fluorescent probe PTC. PTC is ingeniously designed based on a strong intramolecular charge transfer (ICT) effect, exhibiting not only high sensitivity to the microenvironmental polarity (showing a good linear relationship between fluorescence intensity and polarity) but also a remarkably large Stokes shift (>165 nm). We successfully achieved high-fidelity imaging of lysosomal polarity, detected autophagy process, and captured in real-time the dynamic evolution of lysosome. This probe provides a powerful chemical tool for in-depth research into the molecular mechanisms of lysosome-related diseases.