@article{Poller2016, 
author = {Wolfram C. Poller and Evelyn Ramberger and Philipp Boehm-Sturm and Susanne Mueller and Konstantin Möller and Norbert Löwa and Frank Wiekhorst and Susanne Wagner and Matthias Taupitz and Eyk Schellenberger and Gert Baumann and Karl Stangl and Verena Stangl and Antje Ludwig},
title = {Uptake of citrate-coated iron oxide nanoparticles into atherosclerotic lesions in mice occurs via accelerated transcytosis through plaque endothelial cells},
year = {2016},
journal = {Nano Research},
volume = {9},
number = {11},
pages = {3437-3452},
keywords = {atherosclerosis, unstable plaques, magnetic resonance imaging, decreased endothelial barrier function, superparamagnetic iron oxide nanoparticles},
url = {https://www.sciopen.com/article/10.1007/s12274-016-1220-9},
doi = {10.1007/s12274-016-1220-9},
abstract = {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-/-) 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.}
}