Uptake of citrate-coated iron oxide nanoparticles into atherosclerotic lesions in mice occurs via accelerated transcytosis through plaque endothelial cells
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Uptake of citrate-coated iron oxide nanoparticles into atherosclerotic lesions in mice occurs via accelerated transcytosis through plaque endothelial cells
imprint:
Springer Science and Business Media LLC, 2016
Published in:Nano Research
Language:
English
DOI:
10.1007/s12274-016-1220-9
ISSN:
1998-0124;
1998-0000
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title>
<jats:p>Very small superparamagnetic iron oxide nanoparticles (VSOPs) rapidly accumulate in atherosclerotic lesions, thereby enabling plaque visualization by magnetic resonance imaging (MRI). This study was performed to identify the uptake mechanisms of VSOPs into atherosclerotic plaques. Low-density lipoprotein receptor-deficient (LDLR<jats:sup>−/−</jats:sup>) mice with advanced atherosclerosis were analyzed using MRI and transmission electron microscopy (TEM) at various time points after intravenous administration of VSOPs. Post-mortem MRI detected VSOP labeling of atherosclerotic plaques 10 min after injection, and the signal increased over the first 3 h. TEM revealed that the intensive plaque labeling was mediated by accelerated transcytosis of VSOPs through endothelial cells overlaying atherosclerotic lesions. Experiments with endocytosis inhibitors and small interfering RNA (siRNA) revealed a dynamin-dependent mechanism involving both clathrin- and caveolin-mediated processes. In cell culture experiments, endothelial VSOP uptake was enhanced under proatherogenic flow and TNFα stimulation, conditions that are both present in plaque areas. Our study demonstrates that VSOPs enable non-invasive MRI assessment of accelerated endothelial transcytosis, an important pathomechanism in atherosclerotic plaque formation.</jats:p>