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Very small superparamagnetic iron oxide nanoparticles: Long-term fate and metabolic processing in atherosclerotic mice. 2018
Wolfram C Poller, and
Melanie Pieber, and
Philipp Boehm-Sturm, and
Evelyn Ramberger, and
Vasileios Karampelas, and
Konstantin Möller, and
Moritz Schleicher, and
Frank Wiekhorst, and
Norbert Löwa, and
Susanne Wagner, and
Jörg Schnorr, and
Matthias Taupitz, and
Karl Stangl, and
Verena Stangl, and
Antje Ludwig
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany. Electronic address: wolfram.poller@charite.de.
We investigated the biotransformation of very small superparamagnetic iron oxide nanoparticles (VSOP) in atherosclerotic LDLR-/- mice. Transmission electron microscopy revealed an uptake of VSOP not only by macrophages but also by endothelial cells in liver, spleen, and atherosclerotic lesions and their accumulation in the lysosomal compartment. Using magnetic particle spectroscopy (MPS), we show that the majority of VSOP's superparamagnetic iron was degraded within 28 days. MPS spectrum shape indicated changes in the magnetic properties of VSOP during the biodegradation process. Experiments with primary murine bone marrow derived macrophages, primary murine liver sinusoidal endothelial cells, and primary human aortic endothelial cells demonstrated that loading with VSOP induced a differential response of cellular iron homeostasis mechanisms with increased levels of ferritin and iron transport proteins in macrophages and increased levels of ferritin in endothelial cells.
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