Toxicity mechanisms of selected engineered nanoparticles on human neural cells in vitro

Abstract

Environmental exposure to nanoparticles (NPs) has significantly increased in the last decades, mostly due to increased environmental pollution and frequent use of NP containing consumer products. Such NPs may enter our body and cause various health-related problems. The brain is a particularly problematic accumulation site due to its physiological and anatomical restrictions. Several mechanisms of NP neurotoxicity have already been identified, however not enough is known especially regarding toxicity of engineered/industrial NPs. The focus of this in vitro study was on analysis of neurotoxicity of different engineered NPs, with which we come into contact in our daily lives; SiO₂ NPs, food grade (FG) TiO₂ NPs, TiO₂ P25 and silver NPs as examples of industrial NPs, and polyacrylic acid (PAA) coated cobalt ferrite NPs as an example of biomedical NPs. All short term exposure experiments (24-72 h) were performed on SH-SY5Y human neuroblastoma cell line in vitro using higher (25-50 μg/ml) as well as lower (2-10 μg/ml), concentrations that are more relevant for in vivo NPs exposure. We show that NPs can cause neurotoxicity through different mechanisms, such as membrane damage, cell cycle interference, ROS formation and accumulation of autophagosomes, depending on their physico-chemical properties and stability in physiological media. Low, in vivo achievable concentrations of NPs induced only minor or no changes in vitro, however prolonged exposure and accumulation in vivo could negatively affect the cells. This was also shown in case of autophagy dysfunction for TiO₂ P25 NPs and decrease of cell viability for TiO₂ FG NPs, which were only evident after 72 h of incubation.

Keywords: Cell cycle; Internalization; Nanoparticle; Neurotoxicity; ROS; Viability.