Hydrogen Sulfide Donor Featuring Dual-Modal Imaging for the Theranostic Management of Drug-Induced Liver Injury

Drug-induced liver injury (DILI) in diabetes remains a critical and clinically challenging disease due to the lack of effective theranostic tools. Herein, we report SKCLS, a carboxylesterase (CE, an enzyme overexpressed in the liver)-activatable hydrogen sulfide (H₂S) donor integrating near-infrared fluorescence and chemiluminescence (NIRF/CHL) imaging for DILI theranostics in diabetes. Upon CE-mediated hydrolysis, SKCLS undergoes a self-immolative reaction to generate NIRF and CHL signals for the precise tracking of liver repair processes and the release of carbonyl sulfide (COS), which can be rapidly converted to H₂S via carbonic anhydrase (CA). The in situ delivery of H₂S effectively alleviates oxidative injury by activating the Keap1-Nrf2/ARE pathway and accelerates hepatic functional recovery. This study successfully establishes an innovative theranostic platform that combines dual-mode diagnosis and H₂S therapy. It not only effectively solves the theranostic problems associated with DILI management in diabetes but also opens up new avenues for managing other injury-related liver diseases.