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New findings about iron oxide nanoparticles and their different effects on murine primary brain cells

Authors Neubert J, Wagner S, Kiwit J, Bräuer AU, Glumm J

Received 16 September 2014

Accepted for publication 16 October 2014

Published 13 March 2015 Volume 2015:10(1) Pages 2033—2049

DOI https://doi.org/10.2147/IJN.S74404

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Jenni Neubert,1 Susanne Wagner,2 Jürgen Kiwit,3 Anja U Bräuer,1,* Jana Glumm1,3,*

1Institute of Cell Biology and Neurobiology, Center for Anatomy, 2Institute for Radiology, Charité-Universitaetsmedizin Berlin, 3Clinic for Neurosurgery, HELIOS Klinikum Berlin-Buch, Berlin, Germany

*These authors contributed equally to this work

Abstract: The physicochemical properties of superparamagnetic iron oxide nanoparticles (SPIOs) enable their application in the diagnostics and therapy of central nervous system diseases. However, since crucial information regarding side effects of particle–cell interactions within the central nervous system is still lacking, we investigated the influence of novel very small iron oxide particles or the clinically approved ferucarbotran or ferumoxytol on the vitality and morphology of brain cells. We exposed primary cell cultures of microglia and hippocampal neurons, as well as neuron–glia cocultures to varying concentrations of SPIOs for 6 and/or 24 hours, respectively. Here, we show that SPIO accumulation by microglia and subsequent morphological alterations strongly depend on the respective nanoparticle type. Microglial viability was severely compromised by high SPIO concentrations, except in the case of ferumoxytol. While ferumoxytol did not cause immediate microglial death, it induced severe morphological alterations and increased degeneration of primary neurons. Additionally, primary neurons clearly degenerated after very small iron oxide particle and ferucarbotran exposure. In neuron–glia cocultures, SPIOs rather stimulated the outgrowth of neuronal processes in a concentration- and particle-dependent manner. We conclude that the influence of SPIOs on brain cells not only depends on the particle type but also on the physiological system they are applied to.

Keywords: microglia, hippocampal neurons, degeneration, morphology, nanoparticles
 

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