Hypochlorite activatable ratiometric fluorescent probe based on endoplasmic reticulum stress for imaging of atherosclerosis

Abstract

Endoplasmic reticulum (ER) stress can induce reactive oxygen (ROS) generation which is directly associated with the emergence of atherosclerosis. Foam cells could promote atherogenesis by inducing ER stress. To understand hypochlorite (ClO^-) levels in foam cells under ER stress, novel ER-targeted ClO^- activatable ratiometric fluorescence probes Rx-NE and Rx-NCE were designed using a classical rhodamine dye and coumarin dye bridge moiety as the fluorescent skeleton. Both Rx-NE and Rx-NCE demonstrated ratiometric detection capabilities for ClO^-, with Rx-NCE showing better sensitivity compared to Rx-NE. The probe Rx-NCE could detect the upregulation of ClO^- in foam cells under ER stress and clearly outline delineation of the boundary of atherosclerotic plaques by dual-color imaging. Importantly, the hypochlorite-activated ratiometric probe Rx-NCE had been innovatively applied to the distinction of atherosclerotic blood vessels in atherosclerosis-bearing transgenic (tg) (flk1: eGFP) zebrafish. The probe Rx-NCE is of significant value for investigating the pathological role of ER stress and atherosclerotic diseases, as well as offering new insights into the identification of atherosclerosis.

Keywords: Atherosclerosis; Endoplasmic reticulum stress; Foam cells; Hypochlorite-activatable; Ratiometric fluorescence probe.