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Andrea Haase published an article in September 2017.
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(2012 - 2017)
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Article 1 Read 1 Citation Benchmark of Nanoparticle Tracking Analysis on Measuring Nanoparticle Sizing and Concentration Published: 28 September 2017
Journal of Micro and Nano-Manufacturing, doi: 10.1115/1.4037124
One of the greatest challenges in the manufacturing and development of nanotechnologies is the requirement for robust, reliable and accurate characterization data. Presented here are the results of an interlaboratory comparison brought about through multiple rounds of engagement with NanoSight Malvern and 10 pan-European research facilities. Following refinement of the Nanoparticle Tracking Analysis technique, the size and concentration characterization of nanoparticles in liquid suspension was proven to be robust and reproducible for multiple sample types in mono-modal, binary or multi-modal mixtures. The limits of measurement were shown to exceed the 30 nm to 600 nm range (with all system models), with percentage coefficients of variation being calculated as sub 5 % for monodisperse samples. Particle size distributions were also improved through the incorporation of the Finite Track Length Adjustment algorithm, which most noticeably acts to improve the resolution of multimodal sample mixtures. The addition of a software correction to account for variations between instruments also dramatically increased the accuracy and reproducibility of concentration measurements. When combined, the advances brought about during the ILCs allow for the simultaneous determination of accurate and precise nanoparticle sizing and concentration data in one measurement.
Article 2 Reads 2 Citations CompNanoTox2015: novel perspectives from a European conference on computational nanotoxicology on predictive nanotoxicol... Published: 09 August 2017
Nanotoxicology, doi: 10.1080/17435390.2017.1371351
A first European Conference on Computational Nanotoxicology, CompNanoTox, was held in November 2015 in Benahavís, Spain with the objectives to disseminate and integrate results from the European modeling and database projects (NanoPUZZLES, ModENPTox, PreNanoTox, MembraneNanoPart, MODERN, eNanoMapper and EU COST TD1204 MODENA) as well as to create synergies within the European NanoSafety Cluster. This conference was supported by the COST Action TD1204 MODENA on developing computational methods for toxicological risk assessment of engineered nanoparticles and provided a unique opportunity for cross fertilization among complementary disciplines. The efforts to develop and validate computational models crucially depend on high quality experimental data and relevant assays which will be the basis to identify relevant descriptors. The ambitious overarching goal of this conference was to promote predictive nanotoxicology, which can only be achieved by a close collaboration between the computational scientists (e.g. database experts, modeling experts for structure, (eco) toxicological effects, performance and interaction of nanomaterials) and experimentalists from different areas (in particular toxicologists, biologists, chemists and material scientists, among others). The main outcome and new perspectives of this conference are summarized here.
Article 1 Read 3 Citations Genotoxicity testing of different surface-functionalized SiO2, ZrO2 and silver nanomaterials in 3D human bronchial model... Published: 22 June 2017
Archives of Toxicology, doi: 10.1007/s00204-017-2015-9
Inhalation is considered a critical uptake route for NMs, demanding for sound toxicity testing using relevant test systems. This study investigates cytotoxicity and genotoxicity in EpiAirway™ 3D human bronchial models using 16 well-characterized NMs, including surface-functionalized 15 nm SiO2 (4 variants), 10 nm ZrO2 (4), and nanosilver (3), ZnO NM-110, TiO2 NM-105, BaSO4 NM-220, and two AlOOH NMs. Cytotoxicity was assessed by LDH and ATP assays and genotoxicity by the alkaline comet assay. For 9 NMs, uptake was investigated using inductively coupled plasma–mass spectrometry (ICP–MS). Most NMs were neither cytotoxic nor genotoxic in vitro. ZnO displayed a dose-dependent genotoxicity between 10 and 25 µg/cm2. Ag.50.citrate was genotoxic at 50 µg/cm2. A marginal but still significant genotoxic response was observed for SiO2.unmodified, SiO2.phosphate and ZrO2.TODS at 50 µg/cm2. For all NMs for which uptake in the 3D models could be assessed, the amount taken up was below 5% of the applied mass doses and was furthermore dose dependent. For in vivo comparison, published in vivo genotoxicity data were used and in addition, at the beginning of this study, two NMs were randomly selected for short-term (5-day) rat inhalation studies with subsequent comet and micronucleus assays in lung and bone marrow cells, respectively, i.e., ZrO2.acrylate and SiO2.amino. Both substances were not genotoxic neither in vivo nor in vitro. EpiAirway™ 3D models appear useful for NM in vitro testing. Using 16 different NMs, this study confirms that genotoxicity is mainly determined by chemical composition of the core material.
Article 1 Read 3 Citations Quantification of silver nanoparticle uptake and distribution within individual human macrophages by FIB/SEM slice and v... Published: 21 March 2017
Journal of Nanobiotechnology, doi: 10.1186/s12951-017-0255-8
Background Quantification of nanoparticle (NP) uptake in cells or tissues is very important for safety assessment. Often, electron microscopy based approaches are used for this purpose, which allow imaging at very high resolution. However, precise quantification of NP numbers in cells and tissues remains challenging. The aim of this study was to present a novel approach, that combines precise quantification of NPs in individual cells together with high resolution imaging of their intracellular distribution based on focused ion beam/ scanning electron microscopy (FIB/SEM) slice and view approaches. Results We quantified cellular uptake of 75 nm diameter citrate stabilized silver NPs (Ag 75 Cit) into an individual human macrophage derived from monocytic THP-1 cells using a FIB/SEM slice and view approach. Cells were treated with 10 μg/ml for 24 h. We investigated a single cell and found in total 3138 ± 722 silver NPs inside this cell. Most of the silver NPs were located in large agglomerates, only a few were found in clusters of fewer than five NPs. Furthermore, we cross-checked our results by using inductively coupled plasma mass spectrometry and could confirm the FIB/SEM results. Conclusions Our approach based on FIB/SEM slice and view is currently the only one that allows the quantification of the absolute dose of silver NPs in individual cells and at the same time to assess their intracellular distribution at high resolution. We therefore propose to use FIB/SEM slice and view to systematically analyse the cellular uptake of various NPs as a function of size, concentration and incubation time. Keywords Nanoparticles FIB/SEM slice and view Absolute dose Cellular internalization Macrophage
Article 2 Reads 4 Citations The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols a... Published: 01 March 2017
International Journal of Nanomedicine, doi: 10.2147/IJN.S124295
Nanoparticles (NPs) have gained huge interest in the medical field, in particular for drug delivery purposes. However, binding of proteins often leads to fast NP uptake and rapid clearance, thereby hampering medical applications. Thus, it is essential to determine and control the bio–nano interface. This study investigated the serum protein interactions of dendritic polyglycerols (dPGs), which are promising drug delivery candidates by means of two dimensional gel electrophoresis (2DE) in combination with mass spectrometry. In order to investigate the influence of surface charge, sulfated (sulfated dendritic polyglycerol [dPGS]) and non-sulfated (dPGOH) surfaces were applied, which were synthesized on a gold core allowing for easier separation from unbound biomolecules through centrifugation. Furthermore, two different sizes for dPGS were included. Although size had only a minor influence, considerable differences were detected in protein affinity for dPGS versus dPGOH surfaces, with dPGOH binding much less proteins. Cellular uptake into human CD14 monocytes was analyzed by flow cytometry, and dPGOH was taken up to a much lower extent compared to dPGS. By using a pull-down approach, possible cellular interaction partners of serum pre-incubated dPGS-Au20 NPs from the membrane fraction of THP-1 cells could be identified such as for instance the transferrin receptor or an integrin. Clathrin-mediated endocytosis was further investigated using chlorpromazine as an inhibitor, which resulted in a 50% decrease of the cellular uptake of dPGS. This study could confirm the influence of surface charge on protein interactions and cellular uptake of dPGS. Furthermore, the approach allowed for the identification of possible uptake receptors and insights into the uptake mechanism. : sulfated dendritic polyglycerols, protein corona, cellular uptake, uptake receptors, clathrin-mediated endocytosis
BOOK-CHAPTER 1 Read 0 Citations Systems Biology to Support Nanomaterial Grouping Published: 01 January 2017
Advances in Experimental Medicine and Biology, doi: 10.1007/978-3-319-47754-1_6
The assessment of potential health risks of engineered nanomaterials (ENMs) is a challenging task due to the high number and great variety of already existing and newly emerging ENMs. Reliable grouping or categorization of ENMs with respect to hazards could help to facilitate prioritization and decision making for regulatory purposes. The development of grouping criteria, however, requires a broad and comprehensive data basis. A promising platform addressing this challenge is the systems biology approach. The different areas of systems biology, most prominently transcriptomics, proteomics and metabolomics, each of which provide a wealth of data that can be used to reveal novel biomarkers and biological pathways involved in the mode-of-action of ENMs. Combining such data with classical toxicological data would enable a more comprehensive understanding and hence might lead to more powerful and reliable prediction models. Physico-chemical data provide crucial information on the ENMs and need to be integrated, too. Overall statistical analysis should reveal robust grouping and categorization criteria and may ultimately help to identify meaningful biomarkers and biological pathways that sufficiently characterize the corresponding ENM subgroups. This chapter aims to give an overview on the different systems biology technologies and their current applications in the field of nanotoxicology, as well as to identify the existing challenges.