Multifunctional "three-in-one" fluorescent theranostic system for hepatic ischemia- reperfusion injury

Hepatic ischemia-reperfusion injury (HIRI) is the main cause of postoperative liver dysfunction and liver failure. Traditional separation of HIRI diagnosis and therapy confers several disadvantages, including the inability to visualize the therapeutic and asynchronous action. However, developing a versatile material with integrated diagnosis and treatment for HIRI remains a great challenge. Given that hypochlorous acid (HOCl) plays a crucial oxidative role in HIRI, we developed a single-component multifunctional fluorescent theranostic platform (MB-Gly) with a “three-in-one” molecular design incorporating a near-infrared fluorophore methylene blue, glycine and a HOCl-response unit, which could not only provide real-time visualization of HIRI but also boost targeted drug delivery. Using MB-Gly, we were able to achieve real-time and dynamic monitoring of HOCl during HIRI in hepatocytes and mouse livers and reduce the liver damage in hepatocytes and mice. RNA sequencing illustrated the therapeutic role of MB-Gly associated with changes in gene expression related to apoptosis, oxidative stress, metabolism and inflammation. To the best of our knowledge, this is the first multifunctional fluorescent theranostic system for HIRI reported to date. Our smart “three-in-one” approach shines light on the etiology and pathogenesis of HIRI, providing profound insights into the development of potential therapeutic targets.