TY - JOUR A1 - Lichtenstein, D. A1 - Ebmeyer, J. A1 - Meyer, T. A1 - Behr, A.-C. A1 - Kästner, Claudia A1 - Böhmert, L. A1 - Juling, J. A1 - Niemann, B. A1 - Fahrenson, C. A1 - Selve, S. A1 - Thünemann, Andreas A1 - Meijer, J. A1 - Estrela-Lopis, I. A1 - Bräuning, A. A1 - Lampen, A. T1 - It takes more than a coating to get nanoparticles through the intestinal barrier in vitro N2 - Size and shape are crucial parameters which have impact on the potential of nanoparticles to penetrate cell membranes and epithelial barriers. Current research in nanotoxicology additionally focuses on particle coating. To distinguish between core- and coating-related effects in nanoparticle uptake and translocation, two nanoparticles equal in size, coating and charge but different in core material were investigated. Silver and iron oxide nanoparticles coated with poly(acrylic acid) were chosen and extensively characterized by small-angle x-ray scattering, nanoparticle tracing analysis and transmission electron microscopy (TEM). Uptake and transport were studied in the intestinal Caco-2 model in a Transwell System with subsequent elemental analysis. TEM and ion beam microscopy were conducted for particle visualization. Although equal in size, charge and coating, the behavior of the two particles in Caco-2 cells was different: while the internalized amount was comparable, only iron oxide nanoparticles additionally passed the epithelium. Our findings suggest that the coating material influenced only the uptake of the nanoparticles whereas the translocation was determined by the core material. Knowledge about the different roles of the particle coating and core materials in crossing biological barriers will facilitate toxicological risk assessment of nanoparticles and contribute to the optimization of pharmacokinetic properties of nano-scaled pharmaceuticals. KW - Silver KW - Nanoparticle KW - Polymer KW - Polyacrylic acid PY - 2017 U6 - https://doi.org/10.1016/j.ejpb.2016.12.004 SN - 0939-6411 SN - 1873-3441 VL - 118 SP - 21 EP - 29 PB - Elsevier AN - OPUS4-41170 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lichtenstein, D. A1 - Meyer, T. A1 - Böhmert, L. A1 - Juling, S. A1 - Fahrenson, C. A1 - Selve, S. A1 - Thünemann, Andreas A1 - Meijer, J. A1 - Estrela-Lopis, I. A1 - Braeuning, A. A1 - Lampen, A. T1 - Dosimetric quantification of coating-related uptake of silver nanoparticles N2 - The elucidation of mechanisms underlying the cellular uptake of nanoparticles (NPs) is an important topic in nanotoxicological research. Most studies dealing with silver NP uptake provide only qualitative data about internalization efficiency and do not consider NP-specific dosimetry. Therefore, we performed a comprehensive comparison of the cellular uptake of differently coated silver NPs of comparable size in different human intestinal Caco-2 cell-derived models to cover also the influence of the intestinal mucus barrier and uptake-specialized M-cells. We used a combination of the Transwell system, transmission electron microscopy, atomic absorption spectroscopy, and ion beam microscopy techniques. The computational in vitro sedimentation, diffusion, and dosimetry (ISDD) model was used to determine the effective dose of the particles in vitro based on their individual physicochemical characteristics. Data indicate that silver NPs with a similar size and shape show coating-dependent differences in their uptake into Caco-2 cells. The internalization of silver NPs was enhanced in uptake-specialized M-cells while the mucus did not provide a substantial barrier for NP internalization. ISDD modeling revealed a fivefold underestimation of dose–response relationships of NPs in in vitro assays. In summary, the present study provides dosimetry-adjusted quantitative data about the influence of NP coating materials in cellular uptake into human intestinal cells. Underestimation of particle effects in vitro might be prevented by using dosimetry models and by considering cell models with greater proximity to the in vivo situation, such as the M-cell model. KW - Silver nanoparticles KW - Small-angle X-ray scattering KW - Saxs PY - 2017 U6 - https://doi.org/10.1021/acs.langmuir.7b01851 SN - 0743-7463 VL - 33 IS - 45 SP - 13087 EP - 13097 PB - Americal Chemical Society AN - OPUS4-42875 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Stock, V. A1 - Fahrenson, C. A1 - Thünemann, Andreas A1 - Donmez, M. H. A1 - Voss, L. A1 - Bohmert, L. A1 - Braeuning, A. A1 - Lampen, A. A1 - Sieg, H. T1 - Impact of artificial digestion on the sizes and shapes of microplastic particles N2 - Current analyses show a widespread occurrence of microplastic particles in food products and raise the question of potential risks to human health. Plastic particles are widely considered to be inert due to their low chemical reactivity and therefore supposed to pose, if at all only minor hazards. However, variable physicochemical conditions during the passage of the gastrointestinal tract gain strong importance, as they may affect particle characteristics. This study aims to analyze the impact of the gastrointestinal passage on the physicochemical particle characteristics of the five most produced and thus environmentally relevant plastic materials polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate and polystyrene. Scanning electron microscopy (SEM) and subsequent image analysis were employed to characterize microplastic particles. Our results demonstrate a high resistance of all plastic particles to the artificial digestive juices. The present results underline that the main stages of the human gastrointestinal tract do not decompose the particles. This allows a direct correlation between the physicochemical particle characteristics before and after digestion. Special attention must be paid to the adsorption of organic compounds like proteins, mucins and lipids on plastic particles since it could lead to misinterpretations of particle sizes and shapes. KW - Artificial digestion KW - Gastrointestinal barrier KW - Microplastic KW - Oral uptake KW - Particle size PY - 2020 U6 - https://doi.org/10.1016/j.fct.2019.111010 VL - 135 SP - 111010 PB - Elsevier Ltd. AN - OPUS4-49999 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Paul, M. B. A1 - Fahrenson, C. A1 - Givelet, L. A1 - Herrmann, T. A1 - Loescher, K. A1 - Böhmert, L. A1 - Thünemann, Andreas A1 - Braeuning, A. A1 - Sieg, H. T1 - Beyond microplastics ‑ investigation on health impacts of submicron and nanoplastic particles after oral uptake in vitro N2 - The continuously increasing use of plastics is supposed to result in a rising exposure of MNPs to humans. Available data on human health risks of microplastics after oral uptake increased immensely in the past years and indicates very likely only low risks after oral consumption. Concerning nanoplastics, uptake, transport and potential adverse effects after oral uptake are less well understood. This study aims to investigate differences between microplastic particles and particles in the submicron- and nanoscaled size derived from food-relevant polymers with a particle size range consistent with higher potential for cellular uptake, fate, and effects when applied to human intestinal and liver cells. This work includes the development of cellular and subcellular detection methods for synthetic polymeric particles in the micro- and nanometer-range, using Scanning Electron Microscopy, Small-Angle X-ray and Dynamic Light Scattering methods, Asymmetric Flow Field Flow Fractionation, octanol-water fractionation, fluorescence microscopy and flow cytometry. Polylactic acid (250 nm and 2 μm (polydisperse)), melamine formaldehyde (366 nm) and polymethylmethacrylate (25 nm) were thoroughly characterized. The submicro- and nanoplastic test particles showed an increased uptake and transport quantity through intestinal cells. Both types of particles resulted in observed differences of uptake behavior, most likely influenced by different lipophilicity, which varied between the polymeric test materials. Toxic effects were detected after 24 h only in overload situations for the particles in the submicrometer range. This study provides further evidence for gastrointestinal uptake of submicro- and nanoplastics and points towards differences regarding bioavailability between microplastics and smaller plastic particles that may result following the ingestion of contaminated food and beverages. Furthermore, the results reinforce the importance for studying nanoplastics of different materials of varying size, surface properties, polymer composition and hydrophobicity. KW - Small-angle X-ray scattering KW - SAXS KW - nanoparticle PY - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-550741 VL - 2 SP - 1 EP - 19 PB - Springer Nature AN - OPUS4-55074 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -