Assessing Atherosclerosis by Super-Resolution Imaging of HClO in Foam Cells Using a Ratiometric Fluorescent Probe

Atherosclerosis (AS) is the leading cause of cardiovascular disease. Foam cells, with elevated lipid droplets (LDs) and HClO levels, are the main components of the atherosclerotic plaques that are characteristic of AS. Super-resolution imaging can be used to visualize the distribution of LDs in foam cells at the nanometer level, facilitating the identification of LDs and HClO. In the present study, we report the development of a ratiometric fluorescent probe, SFL-HClO, for super-resolution imaging of LDs and HClO. Super-resolution imaging with this probe revealed the precise structure of LDs at the suborganelle level. Moreover, the fluorescence behavior of SFL-HClO on the surface of LDs verified its excellent performance in detecting HClO in the foam cells. SFL-HClO can sequentially and specifically respond to LDs and HClO via "turn-on" and ratiometric signal output, respectively, thus contributing to precise imaging of foam cells. Importantly, we demonstrate that SFL-HClO can be used to report on upregulated HClO in atherosclerotic plaques in the aorta of AS mice, providing a suitable fluorescent tool for early atherosclerotic disease assessment.