College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Biomedical Science, Shandong Normal University, Jinan 250014, P.R. China.
Anal Chem. 2021 May 11;93(18):7110-7117. doi: 10.1021/acs.analchem.1c00815. Epub 2021 Apr 28.
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 this work, we established a two-photon fluorescence imaging method for 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 and paves a way to the diagnosis of early liver fibrosis with accuracy.
肝纤维化可导致肝硬化和肝癌,严重损害肝功能,甚至导致死亡。早期诊断纤维化对于优化治疗方案、提高治愈率极为必要。在肝纤维化的早期阶段,过表达的单胺氧化酶 B(MAO-B)可以作为生物标志物,这对早期肝纤维化的诊断有很大帮助。然而,仍然缺乏理想的策略来精确监测 MAO-B。在这项工作中,我们建立了一种基于双光子荧光成像的 MAO-B 活性检测方法,该方法基于一种简单制备的探针 BiPhAA。BiPhAA 可以在 10 分钟内被 MAO-B 激活,并发出明亮的荧光。据我们所知,这种基于 BiPhAA 的 MAO-B 成像平台比其他当前的检测方法更快。此外,BiPhAA 允许对肝星状细胞(LX-2)中内源性 MAO-B 水平变化进行动态观察。通过双光子荧光成像,我们观察到纤维化小鼠肝组织中的荧光亮度比正常小鼠高六倍,从而成功地区分了纤维化小鼠和正常小鼠。我们的工作为 MAO-B 的成像提供了一种简单、快速和高灵敏度的方法,并为早期肝纤维化的准确诊断开辟了道路。