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DDC: 610 × Subject: Cytotoxicity ×

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    Impact of mucus modulation by N-acetylcysteine on nanoparticle toxicity
    (Amsterdam : Elsevier, 2023) Meziu, Enkeleda; Shehu, Kristela; Koch, Marcus; Schneider, Marc; Kraegeloh, Annette
    Human respiratory mucus is a biological hydrogel that forms a protective barrier for the underlying epithelium. Modulation of the mucus layer has been employed as a strategy to enhance transmucosal drug carrier transport. However, a drawback of this strategy is a potential reduction of the mucus barrier properties, in particular in situations with an increased exposure to particles. In this study, we investigated the impact of mucus modulation on its protective role. In vitro mucus was produced by Calu-3 cells, cultivated at the air-liquid interface for 21 days and used for further testing as formed on top of the cells. Analysis of confocal 3D imaging data revealed that after 21 days Calu-3 cells secrete a mucus layer with a thickness of 24 ± 6 μm. Mucus appeared to restrict penetration of 500 nm carboxyl-modified polystyrene particles to the upper 5–10 μm of the layer. Furthermore, a mucus modulation protocol using aerosolized N-acetylcysteine (NAC) was developed. This treatment enhanced the penetration of particles through the mucus down to deeper layers by means of the mucolytic action of NAC. These findings were supported by cytotoxicity data, indicating that intact mucus protects the underlying epithelium from particle-induced effects on membrane integrity. The impact of NAC treatment on the protective properties of mucus was probed by using 50 and 100 nm amine-modified and 50 nm carboxyl-modified polystyrene nanoparticles, respectively. Cytotoxicity was only induced by the amine-modified particles in combination with NAC treatment, implying a reduced protective function of modulated mucus. Overall, our data emphasize the importance of integrating an assessment of the protective function of mucus into the development of therapy approaches involving mucus modulation.
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    Surface defects reduce Carbon Nanotube toxicity in vitro
    (Amsterdam [u.a.] : Elsevier Science, 2019) Requardt, Hendrik; Braun, Armin; Steinberg, Pablo; Hampel, Silke; Hansen, Tanja
    The cytotoxicity of two different types of Multi-walled Carbon Nanotubes (MWCNTs)in A549 lung epithelial cells and HepG2 hepatocytes was investigated. One MWCNT still contained iron that was used as a catalyst during production, while the other one had all iron removed in a post-production heat treatment resulting in significantly fewer surface defects. The WST-8 assay was applied to test cell viability. To check the integrity of the cell membrane, we performed the lactate dehydrogenases assay (LDH)and measured the cellular production of reactive oxygen species (ROS). Finally, to examine cell proliferation, we conducted a cell cycle analysis. The results showed a dose- and time-dependent decrease in cell viability for both MWCNTs in both cell types. Moreover, a dose- and time-dependent increase in LDH leakage was detected, thereby indicating a decreased membrane integrity. The production of ROS was significantly increased in the case of the heat-treated MWCNTs. The heat-treated MWCNTs showed significantly stronger adverse effects when compared to the non-treated MWCNTs. Additionally, the heat-treated MWCNTs induced a dose-dependent cell cycle arrest in A549 cells. Both MWCNTs induced a significant cytotoxicity, whereby the heat treatment, leading to a decrease in surface defects, further increased the indicated adverse effects. © 2019 The Authors