A novel HClO-activatable lysosome-targeted fluorescent probe for imaging and diagnosis of atherosclerosis

Abstract

Atherosclerosis (AS) is a systemic vascular disease that typically takes decades before overt disease manifests itself. Due to this silent course, it is essential to create disease predictors before clinical lesions develop. In AS, dysfunction of lysosome induced by the accumulation of HClO changes cytokine secretion from macrophages. The formation of foam cells with an elevated HOCl level is regarded as an iconic feature of the early AS lesion. However, fluorescent probes targeting lysosome to monitor the variations of HClO level during the AS procedure have not reported. In this work, we firstly report a lysosome-targeted fluorescence probe, Lys-HClO, for evaluating AS by mapping the fluctuation of HClO with high selectivity and sensitivity. Meanwhile, probe Lys-HClO can be located in lysosome and successfully used to detected endogenous and exogenous HClO in cells. Furthermore, probe Lys-HClO was effectively applied to imaging endogenous HClO in zebrafish. Notably, with the assistance of probe Lys-HClO, we successfully monitored the significant up regulation of HClO in aorta of high-fat diet (HFD) -induced AS. These results indicate that Lys-HClO was a prospective image tool in studying early diagnosis of AS.