A hepatic-ER cascade-targeting probe co-activated by β-Gal and ClO- for monitoring DILI and therapeutic process.

In this work, a hepatic-endoplasmic reticulum (ER) cascade-targeting probe RDM-Gal-ClO was designed and synthesized, and its fluorescence can be co-activated by β-galactosidase (β-Gal) and ClO-, rather than by β-Gal or ClO- alone. RDM-Gal-ClO can selectively monitor β-Gal and ClO- without interference from some related substances, and the detection limit of RDM-Gal-ClO to ClO- can be calculated to be 50 nM in the presence of 10 U β-Gal. Low toxic RDM-Gal-ClO sequentially exhibits good hepatic-targeting ability driven by the specific recognition of galactose on ASGPR, as well as ER-targeting ability driven by the interaction between benzenesulfonamide moiety and sulfonylurea receptors (SUR). Whether at the cellular or animal level, RDM-Gal-ClO can monitor the progression of drug induced liver injury (DILI) in real-time, and the therapeutic process of GSH on APAP-induced DILI, providing a new tool for a deeper understanding of pathological and pharmacological mechanisms of DILI.