title: 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.
abstract: 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.
authors: German Federal Institute for Risk Assessment (BfR), Department of Product Safety, Thielallee 88-92, 14195 Berlin, Germany. andrea.haase@bfr.bund.de
authors: Andrea
authors: A
authors: Haase
authors: Heinrich F
authors: HF
authors: Arlinghaus
authors: Jutta
authors: J
authors: Tentschert
authors: Harald
authors: H
authors: Jungnickel
authors: Philipp
authors: P
authors: Graf
authors: Alexandre
authors: A
authors: Mantion
authors: Felix
authors: F
authors: Draude
authors: Sebastian
authors: S
authors: Galla
authors: Johanna
authors: J
authors: Plendl
authors: Mario E
authors: ME
authors: Goetz
authors: Admir
authors: A
authors: Masic
authors: Wolfgang
authors: W
authors: Meier
authors: Andreas F
authors: AF
authors: Thünemann
authors: Andreas
authors: A
authors: Taubert
authors: Andreas
authors: A
authors: Luch
mesh_terms: D006801:Humans; D008264:Macrophages / Q000737:chemistry* / Q000648:ultrastructure; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D018384:Oxidative Stress; D012834:Silver / Q000032:analysis*; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*; D014116:Toxicology
chemical_list: D012834:Silver