In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury and liver cancer via a near-infrared fluorescent probe

Abstract

The liver, a main detoxification organ, has evolved a complex enzymatic system to respond to multiple pathological conditions, in which leucine aminopeptidase (LAP) has been reported to participate in detoxifying cisplatin in hepatoma cells and contribute to the intrinsic drug resistance. In vivo imaging of LAP activity in liver disease models is thus helpful to further understand the function of LAP in detoxification and medicine, but such an imaging approach is still lacking. Herein, we develop a selective and sensitive near-infrared fluorescent probe (HCAL) for this purpose. Using the probe, combined with confocal fluorescence imaging, we disclose the upregulations of LAP in acetaminophen-induced liver injury and tumor-bearing mice models. Supplementary acetylcysteine can suppress this upregulation, revealing that the LAP increase may be connected with a deficiency in biothiols. Moreover, HCAL has been used to image LAP in hepatoma cells, tumor tissues and xenograft tumor mice models successfully. These results demonstrate that HCAL may be a promising tool for studying the function of LAP in LAP-associated liver diseases.