Accurate diagnosis of hepatic fibrosis with dual detection of nitric oxide and viscosity by a ratiometric fluorescent probe

Abstract

Hepatic fibrosis (HF) is a prevalent and irreversible liver disease caused by unhealthy lifestyles. However, no specific diagnosis tools, except for liver biopsy, are available for HF so far. It was reported that nitric oxide (NO) levels and viscosity in the liver are elevated with HF aggravation, thereby possibly acting as HF biomarkers. Based on this finding, a single-wavelength excited ratiometric fluorescent probe, BDP, was developed as the NO-activated and viscosity-enhanced probe for diagnosing HF first. In the presence of NO, probe BDP exhibited a distinct fluorescence change from red to orange within 12 min. Moreover, the fluorescent intensity of probe BDP could be greatly strengthened in a highly viscous environment. In biological application, probe BDP showed excellent biocompatibility and an ability to ratiometrically image exogenous and endogenous NO in HeLa cells. In addition, more obvious fluorescent signals were observed in cells with increased viscosity induced by nystatin. In particular, the probe accurately diagnosed HF in a mouse model by analyzing ratiometric fluorescence signals.