TY - JOUR A1 - Haase, A. A1 - Mantion, Alexandre A1 - Graf, P. A1 - Plendl, J. A1 - Thünemann, Andreas A1 - Meier, W. A1 - Taubert, A. A1 - Luch, A. T1 - A novel type of silver nanoparticles and their advantages in toxicity testing in cell culture systems JF - Archives of toxicology N2 - Silver nanoparticles (SNPs) are among the most commercialized nanoparticles worldwide. Often SNP are used because of their antibacterial properties. Besides that they possess unique optic and catalytic features, making them highly interesting for the creation of novel and advanced functional materials. Despite its widespread use only little data exist in terms of possible adverse effects of SNP on human health. Conventional synthesis routes usually yield products of varying quality and property. It thus may become puzzling to compare biological data from different studies due to the great variety in sizes, coatings or shapes of the particles applied. Here, we applied a novel synthesis approach to obtain SNP of well-defined colloidal and structural properties. Being stabilized by a covalently linked small peptide, these particles are nicely homogenous, with narrow size distribution, and form monodisperse suspensions in aqueous solutions. We applied these peptide- coated SNP in two different sizes of 20 or 40 nm (Ag20Pep and Ag40Pep) and analyzed responses of THP- 1-derived human macrophages while being exposed against these particles. Gold nanoparticles of similar size and coating (Au20Pep) were used for comparison. The cytotoxicity of particles was assessed by WST-1 and LDH assays, and the uptake into the cells was confirmed via transmission electron microscopy. In summary, our data demonstrate that this novel type of SNP is well suited to serve as model system for nanoparticles to be tested in toxicological studies in vitro. KW - Silver nanoparticles KW - Peptide coating KW - Nanotoxicity PY - 2012 DO - https://doi.org/10.1007/s00204-012-0836-0 SN - 0340-5761 SN - 1432-0738 VL - 86 IS - 7 SP - 1089 EP - 1098 PB - Springer CY - Berlin ; Heidelberg [u.a.] AN - OPUS4-26269 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Haase, A. A1 - Rott, S. A1 - Mantion, Alexandre A1 - Graf, P. A1 - Plendl, J. A1 - Thünemann, Andreas A1 - Meier, W.P. A1 - Taubert, A. A1 - Luch, A. A1 - Reiser, G T1 - Effects of silver nanoparticles on primary mixed neural cell cultures: uptake, oxidative stress and acute calcium responses JF - Toxicological sciences N2 - In the body, nanoparticles can be systemically distributed and then may affect secondary target organs, such as the central nervous system (CNS). Putative adverse effects on the CNS are rarely investigated to date. Here, we used a mixed primary cell model consisting mainly of neurons and astrocytes and a minor proportion of oligodendrocytes to analyze the effects of well-characterized 20 and 40 nm silver nanoparticles (SNP). Similar gold nanoparticles served as control and proved inert for all endpoints tested. SNP induced a strong size-dependent cytotoxicity. Additionally, in the low concentration range (up to 10 µg/ml of SNP), the further differentiated cultures were more sensitive to SNP treatment. For detailed studies, we used low/medium dose concentrations (up to 20 µg/ml) and found strong oxidative stress responses. Reactive oxygen species (ROS) were detected along with the formation of protein carbonyls and the induction of heme oxygenase-1. We observed an acute calcium response, which clearly preceded oxidative stress responses. ROS formation was reduced by antioxidants, whereas the calcium response could not be alleviated by antioxidants. Finally, we looked into the responses of neurons and astrocytes separately. Astrocytes were much more vulnerable to SNP treatment compared with neurons. Consistently, SNP were mainly taken up by astrocytes and not by neurons. Immunofluorescence studies of mixed cell cultures indicated stronger effects on astrocyte morphology. Altogether, we can demonstrate strong effects of SNP associated with calcium dysregulation and ROS formation in primary neural cells, which were detectable already at moderate dosages. KW - Silver nanoparticles KW - Neurons KW - Oxidative stress KW - Protein carbonyls KW - Calcium KW - Reference material KW - Nanoparticle KW - Small-angle X-ray scattering KW - SAXS PY - 2012 DO - https://doi.org/10.1093/toxsci/kfs003 SN - 1096-6080 SN - 1096-0929 VL - 126 IS - 2 SP - 457 EP - 468 PB - Oxford University Press CY - Oxford AN - OPUS4-25633 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -