TY - JOUR A1 - Haase, A. A1 - Arlinghaus, H. F. A1 - Tentschert, J. A1 - Jungnickel, H. A1 - Graf, P. A1 - Mantion, Alexandre A1 - Draude, F. A1 - Galla, S. A1 - Plendl, J. A1 - Goetz, M.E. A1 - Masic, A. A1 - Meier, W. A1 - Thünemann, Andreas A1 - Taubert, A. A1 - Luch, A. T1 - Application of laser postionization secondary neutral mass spectrometry / time-of-flight secondary ion mass spectrometry in nanotoxicology: Visualization of nanosilver in human macrophages and cellular responses N2 - Silver nanoparticles (SNP) are the subject of worldwide commercialization because of their antimicrobial effects. Yet only little data on their mode of action exist. Further, only few techniques allow for visualization and quantification of unlabeled nanoparticles inside cells. To study SNP of different sizes and coatings within human macrophages, we introduce a novel laser postionization secondary neutral mass spectrometry (Laser-SNMS) approach and prove this method superior to the widely applied confocal Raman and transmission electron microscopy. With time-of-flight secondary ion mass spectrometry (TOF-SIMS) we further demonstrate characteristic fingerprints in the lipid pattern of the cellular membrane indicative of oxidative stress and membrane fluidity changes. Increases of protein carbonyl and heme oxygenase-1 levels in treated cells confirm the presence of oxidative stress biochemically. Intriguingly, affected phagocytosis reveals as highly sensitive end point of SNP-mediated adversity in macrophages. The cellular responses monitored are hierarchically linked, but follow individual kinetics and are partially reversible. KW - Nanosilver KW - Laser-SNMS KW - TOF-SIMS KW - Confocal Raman microscopy KW - Oxidative stress KW - Protein carbonyls PY - 2011 DO - https://doi.org/10.1021/nn200163w SN - 1936-0851 VL - 5 IS - 4 SP - 3059 EP - 3068 PB - ACS Publ. CY - Washington, DC, USA AN - OPUS4-23656 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Draude, F. A1 - Galla, S. A1 - Pelster, A. A1 - Tentschert, J. A1 - Jungnickel, H. A1 - Haase, A. A1 - Mantion, Alexandre A1 - Thünemann, Andreas A1 - Taubert, A. A1 - Luch, A. A1 - Arlinghaus, H. F. T1 - ToF-SIMS and laser-SNMS analysis of macrophages after exposure to silver nanoparticles N2 - Silver nanoparticles (SNPs) are among the most commercialized nanoparticles because of their antibacterial effects. Besides being employed, e.g. as a coating material for sterile surfaces in household articles and appliances, the particles are also used in a broad range of medical applications. Their antibacterial properties make SNPs especially useful for wound disinfection or as a coating material for prostheses and surgical instruments. Because of their optical characteristics, the particles are of increasing interest in biodetection as well. Despite the widespread use of SNPs, there is little knowledge of their toxicity. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and laser post-ionization secondary neutral mass spectrometry (Laser-SNMS) were used to investigate the effects of SNPs on human macrophages derived from THP-1 cells in vitro. For this purpose, macrophages were exposed to SNPs. The SNP concentration ranges were chosen with regard to functional impairments of the macrophages. To optimize the analysis of the macrophages, a special silicon wafer sandwich preparation technique was employed; ToF-SIMS was employed to characterize fragments originating from macrophage cell membranes. With the use of this optimized sample preparation method, the SNP-exposed macrophages were analyzed with ToF-SIMS and with Laser-SNMS. With Laser-SNMS, the three-dimensional distribution of SNPs in cells could be readily detected with very high efficiency, sensitivity, and submicron lateral resolution. We found an accumulation of SNPs directly beneath the cell membrane in a nanoparticular state as well as agglomerations of SNPs inside the cells. KW - Laser-SNMS KW - ToF-SIMS KW - Life sciences KW - Imaging KW - Nanoparticles KW - Three-dimensional depth profiling KW - Silver nanoparticle PY - 2013 DO - https://doi.org/10.1002/sia.4902 SN - 0142-2421 SN - 1096-9918 VL - 45 IS - 1 SP - 286 EP - 289 PB - Wiley CY - Chichester AN - OPUS4-27585 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Mantion, Alexandre T1 - New silver nanoparticles with tailored bioactive surface properties as a model for toxicological investigations T2 - Golm International Symposium Bioactive Surfaces CY - Potsdam, Germany DA - 2010-05-20 PY - 2010 AN - OPUS4-21248 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Khare, V. A1 - Li, Z. A1 - Mantion, Alexandre A1 - Ayi, A. A. A1 - Sonkaria, S. A1 - Voelkl, A. A1 - Thünemann, Andreas A1 - Taubert, A. T1 - Strong anion effects on gold nanoparticle formation in ionic liquids N2 - Ionic liquids (ILs) have attracted tremendous interest in the recent past for their potential in many chemical fields. The current report explores the effects of a set of ILs based on the 1-ethyl-3-methyl-imidazolium cation and different anions on the formation of gold nanoparticles. X-Ray diffraction finds face-centered cubic gold in all cases, but transmission electron microscopy (TEM) shows that there are distinct differences in particle formation and stabilization with the ethyl sulfate (ES), trifluoromethanesulfonate (TfO) and methanesulfonate (MS) anions. With the MS anion, nanoparticles with diameters between 5 and 7 nm form, which increasingly aggregate at higher reaction temperatures. With TfO, also small 5 to 7 nm particles form, but only at low temperatures. Above ca. 160 °C, large, ill-defined and aggregated particles form. With ES, polydisperse samples form at all temperatures except 160 °C. In this case the nanoparticles appear often surrounded by an IL film, which appears to stabilize individual, ca. 15 to 20 nm particles. Dynamic light scattering and UV/Vis spectroscopy further show that in suspension the particles are, much like seen in the TEM, more strongly aggregated with higher reaction temperatures. In summary, the results suggest that there are very specific IL-gold interactions that are responsible for the formation of gold particles with an IL-specific shape, size, and aggregation behavior. KW - Ionic liquid templating KW - Gold nanoparticle KW - Ionic liquid PY - 2010 DO - https://doi.org/10.1039/b917467b SN - 0959-9428 SN - 1364-5501 VL - 20 SP - 1332 EP - 1339 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-20872 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Khare, V. A1 - Kraupner, A. A1 - Mantion, Alexandre A1 - Jelicic, A. A1 - Thünemann, Andreas A1 - Giordano, C. A1 - Taubert, A. T1 - Stable iron carbide nanoparticle dispersions in [Emim][SCN] and [Emim][N(CN)2] ionic liquids N2 - Dispersions of Fe3C nanoparticles in several ionic liquids (ILs) have been investigated. The ILs are based on 1-ethyl-3-methylimidazolium [Emim] and 1-butyl-3-methylimidazolium [Bmim] cations. Anions are ethylsulfate [ES], methanesulfonate [MS], trifluoromethylsulfonate (triflate) [TfO], tetrafluoroborate [BF4], dicyanamide [N(CN)2], and thiocyanate [SCN]. Among the ILs studied, [Emim][SCN] and [Emim][N(CN)2] stand out because only in these ILs have stable and transparent nanoparticle dispersions been obtained. All other ILs lead to blackish, slightly turbid dispersions or to completely nontransparent suspensions, which often contain undispersed sediment. UV/vis spectroscopy, transmission electron microscopy, and X-ray scattering suggest that the reason for the stabilization of the Fe3C nanoparticles in [Emim][SCN] is the leaching of traces of iron from the particles (without affecting the crystal structure of the Fe3C particles). The resulting particle surface is thus carbon-rich, which presumably favors the stabilization of the particles. A similar explanation can be postulated for [Emim][N(CN)2], with the dicyanamide anion also being a good ligand for iron. KW - Ionic liquid KW - Iron carbide PY - 2010 DO - https://doi.org/10.1021/la100775m SN - 0743-7463 SN - 1520-5827 VL - 26 IS - 13 SP - 10600 EP - 10605 PB - American Chemical Society CY - Washington, DC AN - OPUS4-21624 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Graf, P. A1 - Mantion, Alexandre A1 - Foelske, A. A1 - Shkilnyy, A. A1 - Masic, A. A1 - Thünemann, Andreas A1 - Taubert, A. T1 - Peptide-coated silver nanoparticles: Synthesis, surface chemistry, and pH-triggered, reversible assembly into particle assemblies N2 - Simple tripeptides are scaffolds for the synthesis and further assembly of peptide/silver nanoparticle composites. Herein, we further explore peptide-controlled silver nanoparticle assembly processes. Silver nanoparticles with a pH-responsive peptide coating have been synthesized by using a one-step precipitation/coating route. The nature of the peptide/silver interaction and the effect of the peptide on the formation of the silver particles have been studied via UV/Vis, X-ray photoelectron, and surface-enhanced Raman spectroscopies as well as through electron microscopy, small angle X-ray scattering and powder X-ray diffraction with Rietveld refinement. The particles reversibly form aggregates of different sizes in aqueous solution. The state of aggregation can be controlled by the solution pH value. At low pH values, individual particles are present. At neutral pH values, small clusters form and at high pH values, large precipitates are observed. KW - Hybrid materials KW - Nano-particles KW - Oligopeptides KW - pH KW - Silver PY - 2009 DO - https://doi.org/10.1002/chem.200802329 SN - 0947-6539 SN - 1521-3765 VL - 15 IS - 23 SP - 5831 EP - 5844 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-19514 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - 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 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 - Tentschert, J. A1 - Jungnickel, H. A1 - Graf, P. A1 - Mantion, Alexandre A1 - Draude, F. A1 - Plendl, J. A1 - Goetz, M.E. A1 - Galla, S. A1 - Masic, A. A1 - Thünemann, Andreas A1 - Taubert, A. A1 - Arlinghaus, H. F. A1 - Luch, A. T1 - Toxicity of silver nanoparticles in human macrophages: uptake, intracellular distribution and cellular responses N2 - Silver nanoparticles (SNP) are among the most commercialized nanoparticles worldwide. They can be found in many diverse products, mostly because of their antibacterial properties. Despite its widespread use only little data on possible adverse health effects exist. It is difficult to compare biological data from different studies due to the great variety in sizes, coatings or shapes of the particles. Here, we applied a novel synthesis approach to obtain SNP, which are covalently stabilized by a small peptide. This enables a tight control of both size and shape. We applied these SNP in two different sizes of 20 or 40 nm (Ag20Pep and Ag40Pep) and analyzed responses of THP-1-derived human macrophages. Similar gold nanoparticles with the same coating (Au20Pep) were used for comparison and found to be non-toxic. We assessed the cytotoxicity of particles and confirmed their cellular uptake via transmission electron microscopy and confocal Raman microscopy. Importantly a majority of the SNP could be detected as individual particles spread throughout the cells. Furthermore we studied several types of oxidative stress related responses such as induction of heme oxygenase I or formation of protein carbonyls. In summary, our data demonstrate that even low doses of SNP exerted adverse effects in human macrophages. KW - Silver nanoparticles KW - Neurotoxicology KW - Protein carbonyls KW - ROS PY - 2011 DO - https://doi.org/10.1088/1742-6596/304/1/012030 SN - 1742-6588 SN - 1742-6596 VL - 304 SP - 012030-1 - 012030-14 PB - IOP Publ. CY - Bristol, UK AN - OPUS4-24035 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tentschert, J. A1 - Draude, F. A1 - Jungnickel, H. A1 - Haase, A. A1 - Mantion, Alexandre A1 - Galla, S. A1 - Thünemann, Andreas A1 - Taubert, A. A1 - Luch, A. A1 - Arlinghaus, H. F. T1 - TOF-SIMS analysis of cell membrane changes in functional impaired human macrophages upon nanosilver treatment N2 - Silver nanoparticles (SNP) are among the most commercialized nanoparticles. Here, we show that peptide-coated SNP cause functional impairment of human macrophages. A dose-dependent inhibition of phagocytosis is observed after nanoparticle treatment, and pretreatment of cells with N-acetyl cysteine (NAC) can counteract the phagocytosis disturbances caused by SNP. Using the surface-sensitive mode of time-of-flight secondary ion mass spectrometry, in combination with multivariate statistical methods, we studied the composition of cell membranes in human macrophages upon exposure to SNP with and without NAC preconditioning. This method revealed characteristic changes in the lipid pattern of the cellular membrane outer leaflet in those cells challenged by SNP. Statistical analyses resulted in 19 characteristic ions, which can be used to distinguish between NAC pretreated and untreated macrophages. The present study discusses the assignments of surface cell membrane phospholipids for the identified ions and the resulting changes in the phospholipid pattern of treated cells. We conclude that the adverse effects in human macrophages caused by SNP can be partially reversed through NAC administration. Some alterations, however, remained. KW - Silver nanoparticles KW - Lipidomics KW - N-acetyl cysteine KW - Phagocytosis KW - Oxidative stress KW - Reference material PY - 2013 DO - https://doi.org/10.1002/sia.5155 SN - 0142-2421 SN - 1096-9918 VL - 45 IS - 1 SP - 483 EP - 485 PB - Wiley CY - Chichester AN - OPUS4-27586 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Nehring, R. A1 - Palivan, C.G. A1 - Moreno-Flores, S. A1 - Mantion, Alexandre A1 - Tanner, P. A1 - Toca-Herrera, J.L. A1 - Thünemann, Andreas A1 - Meier, W. T1 - Protein decorated membranes by specific molecular interactions N2 - Here we characterize new metal-functionalized amphiphilic diblock copolymers, developed for both surface and solution molecular recognition applications. Polybutadiene-block-poly(ethylene oxide) copolymers functionalized with nitrilotriacetic acid and tris(nitrilotriacetic acid) were complexed with nickel(II) to obtain coordination sites for oligohistidine residues of model proteins. Mixtures of functionalized polymers with the respective non-functionalized block copolymers self-assemble in aqueous solution into vesicular structures with a controlled density of the metal end-groups on their surface. In solution, binding of His6-tagged green fluorescent protein (EGFP) and red fluorescent protein (RFP) to the vesicle surface was quantified by fluorescence correlation spectroscopy. Small-angle X-ray scattering indicates an increase of the membrane thickness by 2-3 nm upon protein binding. Block copolymer monolayers at the air-water interface and on solid support served as a model system to characterize the protein-decorated membranes by Brewster angle microscopy and AFM. High resolution AFM of solid-supported, hydrated monolayers indicates that the proteins form densely packed and partially ordered arrays with the cylindrically shaped EGFP molecules lying flat on the surface of the films. KW - Amphiphilic copolymer KW - Metal centers KW - His-tag proteins KW - Molecular recognition PY - 2010 DO - https://doi.org/10.1039/c002838j SN - 1744-683X VL - 6 SP - 2815 EP - 2824 PB - RSC Publ. CY - Cambridge AN - OPUS4-21564 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -