Artikel
Characterizing interactions of very small magnetic iron oxide nanoparticles with murine primary CNS cells
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Veröffentlicht: | 21. Mai 2013 |
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Gliederung
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Objective: The potential use of iron oxide nanoparticles in technical and medical applications is continuously increasing due to their magnetic properties. Particularly with regard to diagnostics (e.g. MRI), toxicological studies in vivo only roughly investigate the influence of iron oxide particles on the clinical phenotype. For this reason our experimental approach aims at studying the effects on physiological parameters of the CNS. Depending on the composition, iron particles are capable to overcome the blood brain barrier and to accumulate in nervous tissue. Accordingly, we want to study the interaction of those particles with the cellular matrix of murine primary CNS cells and potential long-term effects of particle accumulations.
Method: We tested how different particle concentrations (0,5/ 1,5/ 3,0mM) and incubation times (6h, 12h, and 24h) influenced the morphology and vitality of primary CNS cells of mice in vitro. For microglia and astrocyte cultures we sacrificed C57Bl6/J pups (P0-P2). For primary neuronal cultures the hippocampal region of mice embryos (E18) was cultivated. We used monomer coated Very Small Superparamagnetic Iron Oxide Nanoparticles (VSOP; Charité-Universitaetsmedizin Berlin), Resovist® (Bayer Schering Pharma AG) and Feraheme® (AMAG Pharmaceuticals, Inc.). We analyzed the cell cultures by means of morphological stainings, cellular vitality and iron content using fluorescent microscopy and respective software.
Results: Our data show strong interactions of VSOP and Resovist® with microglia. Astrocytes showed slightly weaker interactions and even less showed neurons. We observed only very few to none Feraheme® accumulations in microglia, astrocytes and neurons. In each cell type particles were located in the intracellular space and extracellular we observed recently described, for cell-cell-communication secreted microvesicles. According to increasing iron contents within the cells, we identified elevated cell death.
Conclusions: VSOP, Resovist® and Feraheme® have so far not been reviewed in terms of interactions with CNS tissue and potential adverse effects. Our experiments show, that there is a considerable interference and cytotoxic effects between primary murine CNS cells and applied nanoparticles. The analysis of particle interaction with brain tissue and subsequent effects substantially contribute to the assessment of chances and limits in applications of iron oxide nanoparticles for diagnostics (e.g. MRI) in humans.