Engineering a highly selective probe for ratiometric imaging of H2S n and revealing its signaling pathway in fatty liver disease.

Hydrogen polysulfides (H2S n , n > 1) have continuously been proved to act as important signal mediators in many physiological processes. However, the physiological role of H2S n 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 H2S n . 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 PPG-Np-RhPhCO selectively responds to H2S n , avoiding interaction with biothiol and persulfide. Moreover, this probe was applied to image H2S n in NAFLD for the first time and reveal the H2S n generation pathways in the cell model of drug-treated NAFLD. The pathway of H2S n revealed by PPG-Np-RhPhCO provides significant insights into the roles of H2S n in NAFLD and future drug development.