Engineering a highly selective probe for ratiometric imaging of HS and revealing its signaling pathway in fatty liver disease.

Hydrogen polysulfides (HS , > 1) have continuously been proved to act as important signal mediators in many physiological processes. However, the physiological role of HS and their signaling pathways in complex diseases, such as the most common liver disease, nonalcoholic fatty liver disease (NAFLD), have not been elucidated due to lack of suitable tools for selective detection of intracellular HS . Herein, we adopted a general and practical strategy including recognition site screening, construction of a ratiometric probe and self-assembly of nanoparticles, to significantly improve the probes' selectivity, photostability and biocompatibility. The ratiometric probe selectively responds to HS , avoiding interaction with biothiol and persulfide. Moreover, this probe was applied to image HS in NAFLD for the first time and reveal the HS generation pathways in the cell model of drug-treated NAFLD. The pathway of HS revealed by provides significant insights into the roles of HS in NAFLD and future drug development.