Visualization of the protective role of estrogen against female liver fibrosis via an ER viscosity NIR fluorescent probe

Endoplasmic reticulum (ER) viscosity has emerged as a new potential biomarker for hepatic fibrosis (HF). Herein, we report the first ER-targeting viscosity-responsive near-infrared (NIR) fluorescent probe HBT-PP for investigations of HF pathogenesis. The twisted intramolecular charge transfer (TICT) and the excited state intramolecular proton transfer (ESIPT) are combined to endow HBT-PP with the selective response towards viscosity (∼62-fold) and a super large stokes shift (∼320 nm). HBT-PP mainly targets organelle ER and is able to image the drug- or alcohol-induced viscosity elevation in living cells. Significantly, HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression. Of note, after 10 min of stain with HBT-PP, HF lesions showed a stage-based response, indicating the potential of this probe in fast and early diagnosis of HF. These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.