A novel activatable fluorescent probe for revealing the dynamic of esterase and viscosity during ferroptosis and DILI

Esterase, a hydrolase, is present in a vast variety of animals, plants, and microbes. It has the potential to promote the hydrolysis of diverse esters while also could function as a valid indicator for assessing cell health. Besides, viscosity is a crucial metric for determining the smooth flow state of various biological macromolecules including proteins, polysaccharides, and lipids in the biological system, which is essential for intracellular signaling and interplay among multiple biological elements. Nevertheless, investigating the relationship between esterase activity, and viscosity in several relevant physiological and pathological processes remains challenging, owing to a lack of an appropriate tool. Herein, EaV is a unique multifunctional fluorescent probe that could measure local microviscosity and esterase in live cells via green and red channels at the same time. The utility of EaV for cell imaging was proven by measuring the esterase and viscosity changes in different cell states. More notably, we studied the changes in esterase and viscosity during erastin-induced ferroptosis, detecting for the first time a considerable reduction in esterase activity and an evident elevation in viscosity. In addition, EaV was used to image the changes of viscosity and esterase in the APAP-induced liver damage model. This fluorescence imaging tool revealed a flexible platform capable of highlighting variations of esterase and viscosity in many cellular processes and was also meaningful in further actually applied in more related early diagnosis and medical intervention.