Artikel
Effects of different superparamagnetic iron oxide nanoparticles on the vitality of murine primary brain cells
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Veröffentlicht: | 13. Mai 2014 |
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Gliederung
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Objective: The potential use of nanometer sized superparamagnetic iron oxide particles (IONPs) as MRI contrast agents in medical diagnostics is continuously increasing. IONPs are being investigated to image the pathogenesis of several CNS diseases in vivo. However, sufficient information regarding particle-tissue interactions is lacking and depending on the composition IONPs are capable to overcome the blood brain barrier. Accordingly, we studied the interaction of those particles with the cellular matrix of murine primary CNS cells and potential long-term effects of particle exposure.
Method: We tested the influence of different particle concentrations (0,5/1,5/3,0 mM) and incubation times (6h, 24h) on the morphology and vitality of primary microglia, hippocampal neurons and neuronglia co-cultures in vitro. Microglial cultures were prepared from C57Bl6/J pups (P0-P2), neuronal cultures from mice embryos (E18) and incubated with two monomer coated Very Small Iron Oxide Particles (VSOP-R1/-R2), differing in size or with clinically proven polymer coated Resovist® (Bayer Schering Pharma AG) or Feraheme® (AMAG Pharmaceuticals, Inc.), respectively. We examined cell cultures by means of cell survival, degeneration and morphological alterations using immunocytochemistry, fluorescent microscopy and respective software for statistical analysis.
Results: We observed increased microglial death with increasing IONP exposure times and concentrations, except for Feraheme® that even showed declines in cell death to increasing extents at higher concentrations. Microglia exposed to Resovist® showed highest uptake rates and exposing VSOPs strongly increased cell death. Quantifying primary neurons revealed significant increases of degenerated cells for all tested IONP concentrations, especially for Resovist®. In neuron-glia co-cultures we observed elevated levels of degenerated neurons after incubation with Resovist® and VSOP-R2. Exposing Feraheme® significantly attenuated neuronal branching of neuronal cultures that were least affected by VSOP-R2.
Conclusions: VSOPs, 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 are a considerable interferences and cytotoxic effects between primary murine CNS cells and applied IONPs. The analysis of particle interactions and subsequent effects substantially contribute to the assessment of chances and limits in applications of IONPs for diagnostics (e.g. MRI) in humans.