Chmielewska, A. (2023). Effects of Polystyrene Nanoparticles on Cells of the Neurovascular Unit [Diploma Thesis, Technische Universität Wien]. reposiTUm. https://doi.org/10.34726/hss.2023.101927
quantity of plastic in our environment is growing exponentially due to its increased production, rapidly accumulating plastic waste, and poor recycling systems (Geyer et al., 2017). The awareness of those facts and potential issues connected to them are gaining greater attention due to extensive media coverage and scientific research. Special consideration has been brought to micro- and nanoplastic yielding around 3000 publications on the topic between the years 2016 and 2021 according to a bibliometric analysis using Web of Science’s Core Collection (Sorensen and Jovanović, 2021). There is a growing fear that smaller plastic particles may be more widely dispersed and hazardous than larger ones. However, some basic data is missing for a profound risk assessment of nanoplastic particles such as environmental and human exposure levels or interactions at the cellular level (Brachner et al., 2020). In a recent publication by Leslie et al., the detected cumulative concentration of plastic in human blood yielded around 1.6 g/mL (Leslie et al., 2022). Plastic particles in blood could potentially come into contact with the blood-brain barrier (BBB) and change its functionality or even pass through it, which could have detrimental effects on the central nervous system. This project aimed to evaluate whether nanopolystyrene of different surface chemistry and size can affect the cells of the neurovascular unit: endothelial cells, astrocytes, or pericytes. In the cell viability study, the cells were exposed to various concentrations of nanoplastic for 48 hours. In addition, human cerebral microvascular endothelial cells (hCMEC/D3) and human induced pluripotent stem cell derived brain capillary endothelial-like cells (hiPSC-BCELCs) were cultured on transwell inserts. After the nanoplastic-treatment, changes in the transendothelial electrical resistance (TEER) of the cellular monolayer were recorded. Finally, an uptake study with hCMEC/D3 cells, astrocytes, and pericytes was conducted via exposure to fluorescently labelled selected nanoparticles for 48 hours. The findings demonstrated that only doses markedly greater (300 g/ml or 100 g/ml) than those observed in the blood (Leslie et al., 2022) resulted in decreased cell viability or compromised barrier integrity. The most toxic, out of the tested particle types, turned out to be the PS carboxylated 50 nm and stained aminated 100 nm. It was proven, that both size and zeta potential influence the cell toxicity of nanopolystyrene. It was also determined, that the 50 nm particles have a statistically more harmful effect on the tested cells, than larger – 100 nm nanopolystyrene. Further, this research has shown that the particles' features can drastically alter depending on the matrix they are dispersed in, the length of the incubation, exposure to UV radiation, or even the measurement technique. The experiments revealed that the smaller particles show (50 nm) higher agglomeration tendencies in any considered cell culture medium. The agglomeration of particles determines their internalization potential.
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