In vivo imaging of reactive oxygen species (ROS)-producing pro-inflammatory macrophages in murine carotid atheromas using a CD44-targetable and ROS-responsive nanosensor

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In this study, we report the in vivo imaging of reactive oxygen species (ROS)-overproducing pro-inflammatory macrophages in atherosclerotic plaques using a fluorescent ROS nanosensor. We designed the nanosensor by chemically conjugating hyaluronic acid (HA, a targeting ligand for CD44 receptor), chlorin e6 [Ce6; a near-infrared fluorescent (NIRF) dye], and a thioketal (TK) linker (ROS-degradable linker). The self-assembled nanosensor emitted weak NIRF signals in normal physiological conditions, whereas it emitted strong NIRF signals under ROS-abundant conditions. The cytocompatible nanosensor showed higher intracellular internalization via receptor-mediated endocytosis, which enabled the visualization of intracellular ROS in pro-inflammatory macrophages. Moreover, we demonstrated that the nanosensor enabled the successful targeting and imaging of CD44- and ROS-overproducing pro-inflammatory macrophages in atherosclerotic plaques, as validated by confocal microscopy and immunohistological analyses. These data suggest that our ROS nanosensor is suitable for ROS imaging in pro-inflammatory macrophages in vitro and in vivo and will be a promising approach for imaging atherosclerotic tissues and evaluating the effects of antioxidants.
Publisher
ELSEVIER SCIENCE INC
Issue Date
2020-12
Language
English
Article Type
Article
Citation

JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY, v.92, pp.158 - 166

ISSN
1226-086X
DOI
10.1016/j.jiec.2020.08.034
URI
http://hdl.handle.net/10203/278209
Appears in Collection
ME-Journal Papers(저널논문)
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