Accumulation of Iron Oxide and Silver Nanoparticles in Cultured Glial Cells

Abstract

Iron oxide nanoparticles (IONPs) and silver nanoparticles (AgNPs) are frequently used in everyday products as well as for biomedical applications. As nanoparticles (NPs) are known to cross the intact or damaged blood brain barrier, brain cells have to deal with NPs and NP-derived metal ions. Astrocytes and microglia are the first brain cells that are discussed to encounter NPs which reach the brain, but at the start of this thesis only little was known about the effects of AgNPs or IONPs on those cell types. The consequences of an exposure of astrocytes to AgNPs were studied on astrocyte-rich primary cultures as model systems. These cells efficiently took up AgNPs by endocytotic mechanisms and were neither acutely impaired in their viability nor during prolonged presence of accumulated AgNPs. Neither silver nor AgNPs was exported from the cells but presence of AgNPs in the cells was accompanied by an upregulation of metallothioneins that may safely store AgNP-derived silver ions, thereby protecting astrocytes against the potential toxicity of silver ions. These results are in line with the view that in brain astrocytes efficiently accumulate potentially toxic metals and metal-containing NPs and thereby provide protection for other brain cells. Primary microglial cultures were established and characterized as cell culture model of microglial cells and used to study the effects of an exposure of microglia to IONPs. Fluorescently labelled IONPs were applied to visualize the uptake and intracellular localization of IONPs. These NPs were rapidly taken up by microglia into lysosomal compartments via endocytotic mechanisms. Viable microglia appeared not to suffer from oxidative stress as the cellular glutathione levels remained stable, however, in contrast to astrocytes that had been treated with comparable IONPs, microglia only tolerated moderate concentrations of accumulated IONPs for a few hours before their viability was impaired which may be a consequence of a liberation of iron ions from the accumulated IONPs. The data presented in this thesis support the described differences regarding toxicity and uptake of NPs in astrocytes and microglia. This allows the assumption that astrocytes, due to their high capacity to take up NPs without impairment in their viability, may provide protection for microglial cells which efficiently accumulate NPs but are already damaged by the accumulation of relatively low concentrations.