Rapid Two-Photon Fluorescence Imaging of Monoamine Oxidase B for Diagnosis of Early-Stage Liver Fibrosis in Mice.

Abstract

Liver fibrosis could induce cirrhosis and liver cancer, causing serious damages to liver function and even death. Early diagnosis of fibrosis is extremely requisite for optimizing treatment schedule to improve cure rate. In early-stage fibrosis, overexpressed monoamine oxidase B (MAO-B) can serve as a biomarker, which greatly contributes to the diagnosis of early liver fibrosis. However, there is still a lack of desired strategy to precisely monitor MAO-B in situ. In this work, we established a two-photon fluorescence imaging method for in vivo detection of MAO-B activity counting on a simply prepared probe, BiPhAA. The BiPhAA could be activated by MAO-B within 10 min and fluoresced brightly. To our knowledge, this BiPhAA-based imaging platform for MAO-B is more rapid than other current detection methods. Furthermore, BiPhAA allowed the dynamic observation of endogenous MAO-B level changes in hepatic stellate cells (LX-2). Through two-photon fluorescence imaging, we observed six times higher fluorescence brightness in the liver tissue of fibrosis mice than that of normal mice, thus successfully distinguishing mice with liver fibrosis from normal mice. Our work offers a simple, fast, and highly sensitive approach for imaging MAO-B in situ and paves a way to the diagnosis of early liver fibrosis with accuracy.