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.