Imaging alkaline phosphatase activity in alcoholic liver disease via a rational-designed NIR fluorogenic probe

Alkaline phosphatase is a zinc-based metalloenzyme present in various tissues, and its levels increase in alcoholic liver injury. Herein, we report an enzyme-activatable NIR probe, BDP-R-ALP, that enables highly sensitive and selective detection of alkaline phosphatase activity. At the cellular level, the probe realized real-time imaging of endogenous ALP in ALP-positive HepG2 cells and an alcoholic-liver-disease (ALD) cell model. Furthermore, it enabled tracking of endogenous ALP in a tumor-bearing mouse model. Additionally, two murine models of ALD, simulating hazardous drinking and excessive drinking (a form of alcohol use disorder), were established. BDP-R-ALP allowed non-invasive imaging of alcohol-induced liver injury by reflecting ALP dynamics in these ALD mice, providing a practical tool for ALD diagnosis. Finally, following the administration of a hepatoprotective drug to the model mice, BDP-R-ALP was successfully used to evaluate the therapeutic efficacy of the treatment for ALD.