Affiliation: | 1. 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;2. Charité–Universitätsmedizin Berlin, Department of Experimental Neurology and Center for Stroke Research Berlin, Berlin, Germany;3. Charité–Universitätsmedizin Berlin, NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Berlin, Germany;4. Physikalisch-Technische Bundesanstalt, Berlin, Germany;5. Charité–Universitätsmedizin Berlin, Klinik für Radiologie, Berlin, Germany;6. DZHK (German Centre for Cardiovascular Research), Berlin, Germany;7. Berlin Institute of Health (BIH), Berlin, Germany |
Abstract: | 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. |