A Galactose-Modified Light-Activatable Persulfurated Arene Fluorescent Probe for Targeted Imaging of Polarity and...

Monitoring intracellular physiological changes, particularly the dysregulation of key microenvironmental parameters like viscosity and polarity, provides critical functional insights into diseased states. Herein, we report a fluorescent probe, HTB-βGal, based on persulfurated arenes and sensitive to both polarity and viscosity. Modified with galactose, the probe exhibits good water solubility and is initially non-emissive in aqueous solution. Upon light irradiation, its fluorescence gradually increases due to the photoexcitation-induced aggregation (PEIA) characteristic of the persulfurated arene core. In the H₂O/1,4-dioxane mixture, as the dioxane content rises and the polarity decreases, the probe displays an increase in the fluorescence intensity ratio I₄₈₂/I₅₁₅, accompanied by a gradual increase in overall intensity. In the H₂O/glycerol system, increasing the glycerol content raises the viscosity, which suppresses the rotation of the C-S bond during the PEIA process, thereby enhancing the emission intensity at 500 nm without a significant spectral shift. Unlike conventional probes for polarity and viscosity detection, the photoactivatable fluorescence signal enables remote and controlled activation, ensuring the fidelity of the fluorescence readout. Only signals that change upon light irradiation are recognized as true responses, effectively eliminating false positives arising from fluctuations in cellular autofluorescence or interference from other unknown factors. This strategy significantly enhances detection accuracy. In cellular experiments, the galactose moiety enables targeted delivery to liver cancer cells via interaction with the asialoglycoprotein receptor (ASGPR). Once internalized, the probe accurately monitors changes in the cellular microenvironment, using the increase in the fluorescence intensity ratio between the channels of 405/420-500 nm and 405/500-600 nm for polarity, and enhanced emission of the channel 405/440-540 nm for viscosity.