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 JF - Langmuir 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 DO - 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 - Sieg, H. A1 - Kästner, Claudia A1 - Krause, B. A1 - Meyer, T. A1 - Burel, A. A1 - Böhmert, L. A1 - Lichtenstein, D. A1 - Jungnickel, H. A1 - Tentschert, J. A1 - Laux, P. A1 - Braeuning, A. A1 - Estreal-Lopis, I. A1 - Gauffre, F. A1 - Fessard, V. A1 - Meijer, J. A1 - Luch, A. A1 - Thünemann, Andreas A1 - Lampen, A. T1 - Impact of an artificial digestion procedure on aluminum-containing nanomaterials JF - Langmuir N2 - Aluminum has gathered toxicological Attention based on relevant human exposure and its suspected hazardous potential. Nanoparticles from food supplements or Food contact materials may reach the human gastrointestinal tract. Here, we monitored the physicochemical fate of aluminum containing nanoparticles and aluminum ions when passaging an in vitro model of the human gastrointestinal tract. Smallangle X-ray scattering (SAXS), transmission electron microscopy (TEM), ion beam microscopy (IBM), secondary ion beam mass spectrometry (TOF-SIMS), and inductively coupled plasma mass spectrometry (ICP-MS) in the singleparticle mode were employed to characterize two aluminumcontaining nanomaterials with different particle core materials (Al0, γAl2O3) and soluble AlCl3. Particle size and shape remained unchanged in saliva, whereas strong Agglomeration of both aluminum nanoparticle species was observed at low pH in gastric fluid together with an increased ion release. The levels of free aluminum ions decreased in intestinal fluid and the particles deagglomerated, thus liberating primary particles again. Dissolution of nanoparticles was limited and substantial changes of their shape and size were not detected. The amounts of particle-associated phosphorus, chlorine, potassium, and calcium increased in intestinal fluid, as compared to nanoparticles in standard dispersion. Interestingly, nanoparticles were found in the intestinal fluid after addition of ionic aluminum. We provide a comprehensive characterization of the fate of aluminum nanoparticles in simulated gastrointestinal fluids, demonstrating that orally ingested nanoparticles probably reach the intestinal epithelium. The balance between dissolution and de novo complex formation should be considered when evaluating nanotoxicological experiments. KW - Small-angle X-ray scattering KW - SAXS KW - Nanoparticle PY - 2017 DO - https://doi.org/10.1021/acs.langmuir.7b02729 SN - 1520-5827 SN - 0743-7463 VL - 33 IS - 40 SP - 10726 EP - 10735 PB - Americal Chemical Society AN - OPUS4-42438 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - 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 JF - European Journal of Pharmaceutics and Biopharmaceutics 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 DO - 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 -