TY  - JOUR
A1  - Haase, Andrea
A1  - Rott, Stephanie
A1  - Mantion, Alexandre
A1  - Graf, Philipp
A1  - Plendl, Johanna
A1  - Thünemann, Andreas F.
A1  - Meier, Wolfgang P.
A1  - Taubert, Andreas
A1  - Luch, Andreas
A1  - Reiser, Georg
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 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.
KW  - silver nanoparticles
KW  - neurons
KW  - oxidative stress
KW  - protein carbonyls
KW  - calcium
Y1  - 2012
U6  - https://doi.org/10.1093/toxsci/kfs003
SN  - 1096-6080
VL  - 126
IS  - 2
SP  - 457
EP  - 468
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
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  - Graf, Philipp
A1  - Mantion, Alexandre
A1  - Haase, Andrea
A1  - Thuenemann, Andreas F.
A1  - Masic, Admir
A1  - Meier, Wolfgang P.
A1  - Luch, Andreas
A1  - Taubert, Andreas
T1  - Silicification of peptide-coated silver nanoparticles-A biomimetic soft chemistry approach toward chiral hybrid core-shell materials
JF  - ACS nano
N2  - Silica and silver nanoparticles are relevant materials for new applications in optics, medicine, and analytical chemistry. We have previously reported the synthesis of pH responsive, peptide-templated, chiral silver nanoparticles. The current report shows that peptide-stabilized nanoparticles can easily be coated with a silica shell by exploiting the ability of the peptide coating to hydrolyze silica precursors such as TEOS or TMOS. The resulting silica layer protects the nanoparticles from chemical etching, allows their inclusion in other materials, and renders them biocompatible. Using electron and atomic force microscopy, we show that the silica shell thickness and the particle aggregation can be controlled simply by the reaction time. Small-angle X ray scattering confirms the Ag/peptide@silica core-shell structure. UV-vis and circular dichroism spectroscopy prove the conservation of the silver nanoparticle chirality upon silicification. Biological tests show that the biocompatibility in simple bacterial systems is significantly improved once a silica layer is deposited on the silver particles.
KW  - peptide-templated materials
KW  - silver nanoparticles
KW  - chiral nanoparticles
KW  - Ag/peptide@SiO(2) nanostructures
KW  - core-shell structures
Y1  - 2011
U6  - https://doi.org/10.1021/nn102969p
SN  - 1936-0851
VL  - 5
IS  - 2
SP  - 820
EP  - 833
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Mantion, Alexandre
A1  - Graf, Philipp
A1  - Florea, Ileana
A1  - Haase, Andrea
A1  - Thuenemann, Andreas F.
A1  - Masic, Admir
A1  - Ersen, Ovidiu
A1  - Rabu, Pierre
A1  - Meier, Wolfgang P.
A1  - Luch, Andreas
A1  - Taubert, Andreas
T1  - Biomimetic synthesis of chiral erbium-doped silver/peptide/silica core-shell nanoparticles (ESPN)
JF  - Nanoscale
N2  - Peptide-modified silver nanoparticles have been coated with an erbium-doped silica layer using a method inspired by silica biomineralization. Electron microscopy and small-angle X-ray scattering confirm the presence of an Ag/peptide core and silica shell. The erbium is present as small Er(2)O(3) particles in and on the silica shell. Raman, IR, UV-Vis, and circular dichroism spectroscopies show that the peptide is still present after shell formation and the nanoparticles conserve a chiral plasmon resonance. Magnetic measurements find a paramagnetic behavior. In vitro tests using a macrophage cell line model show that the resulting multicomponent nanoparticles have a low toxicity for macrophages, even on partial dissolution of the silica shell.
Y1  - 2011
U6  - https://doi.org/10.1039/c1nr10930h
SN  - 2040-3364
VL  - 3
IS  - 12
SP  - 5168
EP  - 5179
PB  - Royal Society of Chemistry
CY  - Cambridge
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  - 
TY  - JOUR
A1  - Haase, A.
A1  - Mantion, A.
A1  - Graf, P.
A1  - Plendl, J.
A1  - Thünemann, Andreas F.
A1  - Meier, Wolfgang P.
A1  - Taubert, Andreas
A1  - Luch, A.
T1  - A novel type of silver nanoparticles and their advantages in toxicity testing in cell culture systems
JF  - Archives of toxicology : official journal of EUROTOX
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
Y1  - 2012
U6  - https://doi.org/10.1007/s00204-012-0836-0
SN  - 0340-5761
VL  - 86
IS  - 7
SP  - 1089
EP  - 1098
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Tentschert, J.
A1  - Draude, F.
A1  - Jungnickel, H.
A1  - Haase, A.
A1  - Mantion, Alexandre
A1  - Galla, S.
A1  - Thuenemann, Andreas F.
A1  - Taubert, Andreas
A1  - Luch, A.
A1  - Arlinghaus, H. F.
T1  - TOF-SIMS analysis of cell membrane changes in functional impaired human macrophages upon nanosilver treatment
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 (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
Y1  - 2013
U6  - https://doi.org/10.1002/sia.5155
SN  - 0142-2421
VL  - 45
IS  - 1
SP  - 483
EP  - 485
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Lutze, Jana
A1  - Bañares, Miguel A.
A1  - Pita, Marcos
A1  - Haase, Andrea
A1  - Luch, Andreas
A1  - Taubert, Andreas
T1  - alpha-((4-Cyanobenzoyl)oxy)-omega-methyl poly(ethylene glycol)
BT  - a new stabilizer for silver nanoparticles
JF  - Beilstein journal of nanotechnology
N2  - The article describes the synthesis and properties of alpha-((4-cyanobenzoyl)oxy)-omega-methyl poly(ethylene glycol), the first poly(ethylene glycol) stabilizer for metal nanoparticles that is based on a cyano rather than a thiol or thiolate anchor group. The silver particles used to evaluate the effectiveness of the new stabilizer typically have a bimodal size distribution with hydrodynamic diameters of ca. 13 and ca. 79 nm. Polymer stability was evaluated as a function of the pH value both for the free stabilizer and for the polymers bound to the surface of the silver nanoparticles using H-1 NMR spectroscopy and zeta potential measurements. The polymer shows a high stability between pH 3 and 9. At pH 12 and higher the polymer coating is degraded over time suggesting that alpha-((4-cyanobenzoyl) oxy)-omega-methyl poly(ethylene glycol) is a good stabilizer for metal nanoparticles in aqueous media unless very high pH conditions are present in the system. The study thus demonstrates that cyano groups can be viable alternatives to the more conventional thiol/thiolate anchors.
KW  - cyano anchor group
KW  - poly(ethylene glycol)
KW  - polymer coating
KW  - silver nanoparticles
Y1  - 2017
U6  - https://doi.org/10.3762/bjnano.8.67
SN  - 2190-4286
VL  - 8
SP  - 627
EP  - 635
PB  - Beilstein-Institut zur Förderung der Chemischen Wissenschaften
CY  - Frankfurt, Main
ER  - 
TY  - JOUR
A1  - Tentschert, Jutta
A1  - Jungnickel, Harald
A1  - Reichardt, Philipp
A1  - Leube, Peter
A1  - Kretzschmar, Bernd
A1  - Taubert, Andreas
A1  - Luch, A.
T1  - Identification of nano clay in composite polymers
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  - Industrialized food production is in urgent search for alternative packaging materials, which can serve the requirements of a globalized world in terms of longer product shelf lives, reduced freight weight to decrease transport costs, and better barrier functionality to preserve its freshness. Polymer materials containing organically modified nano clay particles as additives are one example for a new generation of packaging materials with specific barrier functionality to actually hit the market. Clay types used for these applications are aluminosilicates, which belong to the mineral group of phyllosilicates. These consist of nano-scaled thin platelets, which are organically modified with quaternary ammonium compounds acting as spacers between the different clay layers, thereby increasing the hydrophobicity of the mineral additive. A variety of different organically modified clays are already available, and the use as additive for food packaging materials is one important application. To ensure valid risk assessments of emerging nano composite polymers used in the food packaging industry, exact analytical characterization of the organically modified clay within the polymer matrix is of paramount importance. Time-of-flight SIMS in combination with multivariate statistical analysis was used to differentiate modified clay reference materials from another. Time-of-flight SIMS spectra of a reference polymer plate, which contained one specific nano clay composite, were acquired. For each modified clay additive, a set of characteristic diagnostic ions could be identified, which then was used to successfully assign unknown clay additives to the corresponding reference material. Thus, the described methodology could be used to define and characterize nano clay within polymer matrices. Copyright (c) 2014 John Wiley & Sons, Ltd.
KW  - ToF-SIMS
KW  - nanoparticles
KW  - nano clay
KW  - polymer
KW  - food contact material
Y1  - 2014
U6  - https://doi.org/10.1002/sia.5546
SN  - 0142-2421
SN  - 1096-9918
VL  - 46
SP  - 334
EP  - 336
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Maharjan, Romi Singh
A1  - Singh, Ajay Vikram
A1  - Hanif, Javaria
A1  - Rosenkranz, Daniel
A1  - Haidar, Rashad
A1  - Shelar, Amruta
A1  - Singh, Shubham Pratap
A1  - Dey, Aditya
A1  - Patil, Rajendra
A1  - Zamboni, Paolo
A1  - Laux, Peter
A1  - Luch, Andreas
T1  - Investigation of the associations between a nanomaterial's microrheology and toxicology
JF  - ACS omega / American Chemical Society
N2  - With the advent of Nanotechnology, the use of nanomaterials in consumer products is increasing on a daily basis, due to which a deep understanding and proper investigation regarding their safety and risk assessment should be a major priority. To date, there is no investigation regarding the microrheological properties of nanomaterials (NMs) in biological media. 
In our study, we utilized in silico models to select the suitable NMs based on their physicochemical properties such as solubility and lipophilicity. Then, we established a new method based on dynamic light scattering (DLS) microrheology to get the mean square displacement (MSD) and viscoelastic property of two model NMs that are dendrimers and cerium dioxide nanoparticles in Dulbecco's Modified Eagle Medium (DMEM) complete media at three different concentrations for both NMs. Subsequently, we established the cytotoxicological profiling using water-soluble tetrazolium salt-1 (WST-1) and a reactive oxygen species (ROS) assay. 
To take one step forward, we further looked into the tight junction properties of the cells using immunostaining with Zonula occluden-1 (ZO-1) antibodies and found that the tight junction function or transepithelial resistance (TEER) was affected in response to the microrheology and cytotoxicity. The quantitative polymerase chain reaction (q-PCR) results in the gene expression of ZO-1 after the 24 h treatment with NPs further validates the findings of immunostaining results. 
This new method that we established will be a reference point for other NM studies which are used in our day-to-day consumer products.
Y1  - 2022
U6  - https://doi.org/10.1021/acsomega.2c00472
SN  - 2470-1343
VL  - 7
IS  - 16
SP  - 13985
EP  - 13997
PB  - ACS Publications
CY  - Washington, DC
ER  -