@article{HaaseArlinghausTentschertetal.2011,
  author    = {Haase, Andrea and Arlinghaus, Heinrich F. and Tentschert, Jutta and Jungnickel, Harald and Graf, Philipp and Mantion, Alexandre and Draude, Felix and Galla, Sebastian and Plendl, Johanna and Goetz, Mario E. and Masic, Admir and Meier, Wolfgang P. and Thuenemann, Andreas F. and Taubert, Andreas and Luch, Andreas},
  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},
  series = {ACS nano},
  volume    = {5},
  journal   = {ACS nano},
  number    = {4},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1936-0851},
  doi       = {10.1021/nn200163w},
  pages     = {3059 -- 3068},
  year      = {2011},
  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.},
  language  = {en}
}
@article{HaaseRottMantionetal.2012,
  author    = {Haase, Andrea and Rott, Stephanie and Mantion, Alexandre and Graf, Philipp and Plendl, Johanna and Th{\"u}nemann, Andreas F. and Meier, Wolfgang P. and Taubert, Andreas and Luch, Andreas and Reiser, Georg},
  title     = {Effects of silver nanoparticles on primary mixed neural cell cultures: Uptake, oxidative stress and acute calcium responses},
  series = {Toxicological sciences},
  volume    = {126},
  journal   = {Toxicological sciences},
  number    = {2},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1096-6080},
  doi       = {10.1093/toxsci/kfs003},
  pages     = {457 -- 468},
  year      = {2012},
  abstract  = {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 mu g/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 mu g/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.},
  language  = {en}
}