TY - JOUR A1 - Haase, Andrea A1 - Arlinghaus, Heinrich F. A1 - Tentschert, Jutta A1 - Jungnickel, Harald A1 - Graf, Philipp A1 - Mantion, Alexandre A1 - Draude, Felix A1 - Galla, Sebastian A1 - Plendl, Johanna A1 - Goetz, Mario E. A1 - Masic, Admir A1 - Meier, Wolfgang P. A1 - Thuenemann, Andreas F. A1 - Taubert, Andreas A1 - Luch, Andreas 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 JF - ACS nano 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 Y1 - 2011 U6 - https://doi.org/10.1021/nn200163w SN - 1936-0851 VL - 5 IS - 4 SP - 3059 EP - 3068 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Draude, F. A1 - Galla, S. A1 - Pelster, Axel A1 - Tentschert, J. A1 - Jungnickel, H. A1 - Haase, Alfred A1 - Mantion, Alexandre A1 - Thuenemann, Andreas F. A1 - Taubert, Andreas A1 - Luch, A. A1 - Arlinghaus, H. F. T1 - ToF-SIMS and Laser-SNMS analysis of macrophages after exposure to silver nanoparticles JF - Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films N2 - Silver nanoparticles (SNPs) are among the most commercialized nanoparticles because of their antibacterial effects. Besides being employed, e. g. as a coatingmaterial 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 Y1 - 2013 U6 - https://doi.org/10.1002/sia.4902 SN - 0142-2421 VL - 45 IS - 1 SP - 286 EP - 289 PB - Wiley-Blackwell CY - Hoboken ER -