In Vivo Fluorescent Labeling of Foam Cell-Derived Extracellular Vesicles as Circulating Biomarkers for In Vitro Detection of Atherosclerosis

Abstract

Real-time monitoring of the development of atherosclerosis (AS) is key to the management of cardiovascular disease (CVD). However, existing laboratory approaches lack sensitivity and specificity, mostly due to the dearth of reliable AS biomarkers. Herein, we developed an in vivo fluorescent labeling strategy that allows specific staining of the foam cell-derived extracellular vesicles (EVs) in atherosclerotic plaques, which are released into the blood as circulating biomarkers for in vitro detection of AS. This strategy relies on a self-assembled nanoprobe that could recognize foam cells specifically, where the probe is degraded by the intracellular HClO to produce a trifluoromethylbearing boron-dipyrromethene fluorophore (termed B-CF 3 ), a lipophilic dye that can be transferred to the exosomal membranes. These circulating B-CF 3 -stained EVs can be detected directly on a fluorescence spectrometer or microplate reader without resorting to any sophisticated analytical method. This liquid-biopsy format enables early detection and real-time differentiation of lesion vulnerability during AS progression, facilitating effective CVD management.

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

“… 223 To further facilitate detection, the investigators also monitored circulating stained EVs by specifically staining atherosclerotic plaque (AS) foam cell‐derived exosomes directly in the circulation by fluorescence spectrometry or zymography, enabling early detection and real‐time differentiation of lesion vulnerability during AS progression, thereby facilitating effective CVD management. 224 …”