TY - JOUR A1 - Sieg, H. A1 - Krause, B.-C. A1 - Kästner, Claudia A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Tentschert, J. A1 - Jungnickel, H. A1 - Laux, P. A1 - Braeuning, A. A1 - Fessard, V. A1 - Thünemann, Andreas A1 - Luch, A. A1 - Lampen, A. T1 - Cellular Effects of In Vitro-Digested Aluminum Nanomaterials on Human Intestinal Cells N2 - Aluminum (Al) can be taken up from food, packaging, or the environment and thus reaches the human gastrointestinal tract. Its toxic potential after oral uptake is still discussed. The fate of different solid and ionic Al species during the passage through the digestive tract is the focus of this research, as well as the cellular effects caused by these different Al species. The present study combines the physicochemical processing of three recently studied Al species (metallic Al0, mineral Al2O3, and soluble AlCl3) in artificial digestion fluids with in vitro cell systems for the human intestinal barrier. Inductively coupled plasma mass spectrometry (ICP-MS) and small-angle X-ray scattering (SAXS) methods were used to characterize the Al species in the artificial digestion fluids and in cell culture medium for proliferating and differentiated intestinal Caco-2 cells. Cytotoxicity testing and cellular impedance measurements were applied to address the effects of digested Al species on cell viability and cell proliferation. Microarray-based transcriptome analyses and quantitative real-time PCR were conducted to obtain a deeper insight into cellular mechanisms of action and generated indications for cellular oxidative stress and an influence on xenobiotic metabolism, connected with alterations in associated signaling pathways. These cellular responses, which were predominantly caused by formerly ionic Al species and only at very high concentrations, were not impacted by artificial digestion. A two-directional conversion of Al between ionic species and solid particles occurred throughout all segments of the gastrointestinal tract, as evidenced by the presence of nanoscaled particles. Nevertheless, this presence did not increase the toxicity of the respective Al species. KW - SAXS KW - Small-angle X-ray scattering KW - Nanoparticle PY - 2020 U6 - https://doi.org/10.1021/acsanm.9b02354 VL - 3 IS - 3 SP - 2246 EP - 2256 PB - American Chemical Society AN - OPUS4-50632 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Krause, B. A1 - Meyer, T. A1 - Sieg, H. A1 - Kästner, Claudia A1 - Reichardt, P. A1 - Tentschert, J. A1 - Jungnickel, H. A1 - Estrela-Lopis, I. A1 - Burel, A. A1 - Chevance, S. A1 - Gauffre, F. A1 - Jalili, P. A1 - Meijer, J. A1 - Böhmert, L. A1 - Braeuning, A. A1 - Thünemann, Andreas A1 - Emmerling, Franziska A1 - Fessard, V. A1 - Laux, P. A1 - Lampen, A. A1 - Luch, A. T1 - Characterization of aluminum, aluminum oxide and titanium dioxide nanomaterials using a combination of methods for particle surface and size analysis N2 - The application of appropriate analytical techniques is essential for nanomaterial (NM) characterization. In this study, we compared different analytical techniques for NM analysis. Regarding possible adverse health effects, ionic and particulate NM effects have to be taken into account. As NMs behave quite differently in physiological media, special attention was paid to techniques which are able to determine the biosolubility and complexation behavior of NMs. Representative NMs of similar size were selected: aluminum (Al0) and aluminum oxide (Al2O3), to compare the behavior of metal and metal oxides. In addition, titanium dioxide (TiO2) was investigated. Characterization techniques such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were evaluated with respect to their suitability for fast characterization of nanoparticle dispersions regarding a particle's hydrodynamic diameter and size distribution. By application of inductively coupled plasma mass spectrometry in the single particle mode (SP-ICP-MS), individual nanoparticles were quantified and characterized regarding their size. SP-ICP-MS measurements were correlated with the information gained using other characterization techniques, i.e. transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). The particle surface as an important descriptor of NMs was analyzed by X-ray diffraction (XRD). NM impurities and their co-localization with biomolecules were determined by ion beam microscopy (IBM) and confocal Raman microscopy (CRM). We conclude advantages and disadvantages of the different techniques applied and suggest options for their complementation. Thus, this paper may serve as a practical guide to particle characterization techniques. KW - Small-angle X-ray scattering KW - SAXS PY - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-447057 SN - 2046-2069 VL - 8 IS - 26 SP - 14377 EP - 14388 PB - The Royal Society of Chemistry AN - OPUS4-44705 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Sieg, H. A1 - Braeuning, C. A1 - Kunz, B. M. A1 - Daher, H. A1 - Kästner, C. A1 - Krause, B.-C. A1 - Meyer, T. A1 - Jalili, P. A1 - Kogeveen, K. A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Burel, A. A1 - Chevance, S. A1 - Jungnickel, H. A1 - Tentschert, J. A1 - Laux, P. A1 - Braeuning, A. A1 - Gauffre, F. A1 - Fessard, V. A1 - Meijer, J. A1 - Estrela-Lopis, I. A1 - Thünemann, Andreas A1 - Luch, A. A1 - Lampen, A. T1 - Uptake and molecular impact of aluminum-containing nanomaterials on human intestinal caco-2 cells N2 - Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of Action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than Al2O3 nanoparticles, while AlCl3 showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 mg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related. KW - Small-angle x-ray scattering KW - SAXS KW - Nanopatricle PY - 2018 U6 - https://doi.org/10.1080/17435390.2018.1504999 SN - 1743-5390 VL - 12 IS - 9 SP - 992 EP - 1013 PB - Taylor & Francis AN - OPUS4-47432 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -