Engineering of Reversible Luminescent Probes for Real-Time Intravital Imaging of Liver Injury and Repair

Abstract

As the major organ for drug metabolism and detoxification, the liver is prone to damage and severely impaired functionality. The treatment of liver diseases is based on a clear understanding of the process underlying liver injury and repair. However, intravital real-time imaging of liver injury and repair is still limited due to the lack of in vivo reversible visualization methods. To this end, we proposed a rational design strategy for the development of a reversible upconversion luminescence nanoprobe that allows real-time and in vivo imaging of liver injury and repair processes. As a proof of concept, we first developed a small molecule probe NB3 which can reversibly respond to related analytes of early liver injury [peroxynitrite (ONOO-)] and liver repair [glutathione (GSH)]. The small molecule probe was then integrated with a core-shell upconversion nanoparticle to form a sophisticated nanoprobe. Compared with traditional small molecule probes, this nanoprobe exhibited a higher selectivity to ONOO-, longer retention time in liver, and wider dynamic response range to GSH after oxidation by ONOO-. The novel nanoprobe facilitated the successful monitoring and discrimination among the different degrees of liver injury and repair in a mouse model.