Enhanced Integrative Diagnosis and Therapeutic Strategy for Hepatic Ischemia-Reperfusion Injury through HOCl-Sensitive Cysteine Delivery System for Targeted Antioxidant Modulation

Hepatic ischemia-reperfusion injury (HIRI) is a major cause of postoperative liver insufficiency and liver failure, and its pathological process is closely related to the synergistic dysregulation of oxidative stress. Currently, the diagnosis of HIRI is separated from its treatment, making it difficult to achieve effective intervention for HIRI progression. Considering that HOCl is an important upregulated marker at HIRI sites, this study developed an integrated diagnostic and therapeutic strategy based on HOCl-activated cysteine release. The designed smart molecular system, which specifically responds to HOCl via a urea bond, monitors real-time elevated HOCl levels through enhanced fluorescent signals. Meanwhile, the HOCl-activated release of cysteine and methylene blue significantly inhibited oxidative stress injury by scavenging reactive oxygen species (ROS) at the HIRI site, leading to a notable improvement in liver function indicators. This study is the first to combine the HOCl response with cysteine release to achieve antioxidant pathway regulation, which provides an innovative idea and effective strategy for the precise diagnosis and treatment of HIRI.