The aim of our group is to acquire a mechanistic understanding on the interaction of particulate materials with biological barriers. In particular, we are interested in the correlation of physicochemical particle properties with barrier translocation and biological effects in order to support the safe design of particles and the development of novel particle-based therapeutic concepts.
The placental barrier is a key focus of the group considering the exceptional vulnerability of the developing conceptus and the substantial knowledge gap in this field of research. To obtain predictive results, we develop and use advanced human in vitro and ex vivo placental models, which take into account the unique structure/function and the particular microenvironment of the human placenta. Our expertise encompasses dual ex vivo placenta perfusion studies, perfused transwell systems, organotypic 3D microtissue models, isolation of primary cells (e.g. trophoblasts) as well as strong competences in working with particulate materials.
Development of advanced barrier models
We develop and use advanced in vitro and ex vivo models to address particle effects and translocation at biological barriers, focussing on the placenta, intestine and lung. Importantly, we employ tissues or cells of human origin to circumvent uncertainties in extrapolation of animal data. Our strategies to improve the predictive value of the models include the use of primary cells, co-cultures, inclusion of mucus, 3D models or the recreation of a dynamic microenvironment. In the last years, we have succesfully developed and verified two first-in-field advanced in vitro models for the human placental barrier (organotypic 3D placental co-culture microtissues and a co-culture transwell model) and gained extensive expertise in the ex vivo perfusion of human term placentas. Currently, we are investigating into the engineering of new electrospun membranes for improved biobarrier models and collaborate to develop a microphysiological placenta-embryo models and to establish healthy and streptococcus pneumoniae infected primary human airway epothelial cultures. This research has received funding from the 7th Framework Program of the European Comission (EC-FP7-MARINA-263215 and EC-FP7-NANOSOLUTIONS-309329) and the BMBF-project NanoUmwelt (03X0150).
Understanding particles-barrier interactions
Nanoscale materials exhibit unique properties and are envisaged to enable a wealth of novel applications in many fields. A comprehensive understanding of potential human health risks is a prerequisite to the safe and sustainable use of these promising materials.
Biological barriers perform essential protective and supportive functions and are thus potentially prone to damage from nanomaterials exposure. In addition, understanding if and how particle properties can be employed to steer particle barrier interaction and effects is a prerequisite for the development of safe and effective particle-based therapies e.g. to treat the mother, the fetus or placental disorders with reduced off-target effects. We aim to achieve new mechanistic insights into particle-barrier interactions using our advanced biobarrier models, extensive material knowhow and access to state-of-the art analytics. Besides acute and long-term effects, we further expand our reserach to include disease models, co-exposure of nanomaterials and xenobiotics and indirect developmental toxicity mechanisms. This research is supported by funding from the Swiss National Science Foundation (31003A-179337) and received previous founding by the 7th Framework Program of the European Comission (EC-FP7-MARINA-263215 and EC-FP7-NANOSOLUTIONS-309329) and the BMBF-project NanoUmwelt (03X0150).
Graphene related materials@barriers
Graphene and graphene-related materials (GRM) exhibit enormous technological potential, especially in the field of electronics, photonics, optoelectronics and composites, but also for biomedical applications. Nevertheless, the GRM safety landscape is not fully explored yet. The aim of our activities within the Graphene flagship project is to obtain a systematic understanding of the impact of GRM on human cells and biological barriers with respect to the physicochemical properties of the materials. Current investigations focus on the air-blood barrier in the lungs, the intestinal barrier and the placental barrier. Moreover, we investigate the release of GRMs from reinforced composites upon mechanical abrasion or thermal decomposition. This research is supported by funding from European Union 7th Framework Program Graphene Flagship project (EU-Graphene Flagship n°604391), the EU Horizon2020 Framework Graphene Flagship project GrapheneCore1, Core 2 and Core 3(n°696656 and 785219 and n°881603) and the Swiss National Science Foundation.
Dr. Tina Buerki-Thurnherr, Group Leader Particles@barriers
Alma Mater: ETH Zurich
Keywords: Nanotoxicology, Nanoparticle Translocation, Placenta, Advanced In Vitro Models, Primary Cell Culture
Savvina Chortarea, Postdoc
Alma Mater: University of Fribourg
Keywords: Realistic Nanosafety Assessment, Lung, Carbon Nanotubes, Gold Nanoparticles
Leonie Aengenheister, Postdoc
Alma Mater: ETH Zurich
Keywords: Advanced placenta models, Particles-Placenta interactions, Nanosafety
Yvette Hannig, Technical Expert
Keywords: Ex vivo Placenta Perfusion, Nanotoxicology, Microscopy, Cell Biology
Woranan Netkueakul, PhD Student
Alma Mater: ETH Zurich
Keywords: Graphene-composites, Abrasion, Nanosafety, Lung
Lea Furer, PhD Student
Alma Mater: ETH Zurich
Keywords: Membranes, Electrospinning, Advanced co-culture models
Battuja Batbajar Dugershaw, PhD Student
Alma Mater: ETH Zurich
Keywords: Nanosafety, Indirect toxicity, Placental barrier
Ms. Angela Diaz Abad, Universidad de Castilla-La Mancha. UCLM, MSc Student, 2020-2021
Ms. Daria Korejwo, AMI Fribourg, PhD Student, 2016-2020
Dr. Claudia Hempt, ETH Zurich, PhD Student, 2016-2020
Mr. Ogul Can Kuru, Polytecnico di Milano, MSc Student 2019
Mr. Pius Manser, Technical expert, 1984-2019
Dr. Leonie Aengenheister, ETH Zurich, PhD Student 2015-2018
Mr. Erminio Di Renzo, ETH Zurich, MSc Student 2017-2018
Dr. Melanie Kucki, University of Kassel, Research Associate 2013-2017
Dr. Carina Muoth, University of Zurich, PhD Student 2013-2016
Mr. Chasper Gmünder, ETH Zurich, Project student 2014
L. Mathiesen, T. Buerki-Thurnherr, J. Pastuschek, L. Aengenheister, LE. Knudsen. (2021). Fetal exposure to environmental chemicals; insights from placental perfusion studies. Placenta, DOI: 10.1016/j.placenta.2021.01.025.
L. Aengenheister, RR. Favaro, DM. Morales-Prieto, LA. Furer, M. Gruber, C. Wadsack, UR. Markert, T. Buerki-Thurnherr. (2020). Reserach on nanoparticles in human perfused placenta: state of the art and perspectives. Placenta, 104, 199-207.
C. Hempt, C. Hirsch, Y. Hannig, A. Rippl, P. Wick, T. Buerki-Thurnherr. (2020). Investigating the effects of differently produced synthetic amorphous silica (E551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model. Arch Toxicol, DOI: 0.1007/s00204-020-02957-2.
BB. Dugershaw, L. Aengenheister, S. Schmidt Kjolner Hansen, K. Sorig Hougaard, T. Buerki-Thurnherr. (2020). Recent insights on indirect mechanisms in developmental toxicity of nanomaterials. Part Fibre Toxicol., 17, 31 (2020).
W. Netkueakul, D. Korejwo, T. Hammer, S. Chortarea, P. Rupper, O. Braun, M. Calame, B. Rothen-Rutishauser, T. Buerki-Thurnherr, P. Wick, J. Wang. (2020). Release of graphene-related materials from epoxy-based composites: characterization, quantification and hazard assessment in vitro. Nanoscale, 2020,12,10703-10722.
C. Hempt, JP. Kaiser, O. Scholder, T. Buerki-Thurnherr, H. Hofmann, A. Rippl, TB. Schuster, P. Wick, C. Hirsch. (2020). The imapct of synthetic amorphouse silica (E551) on differentiated Caco-2 cells, a model for the human intestinal epithelium. Toxicol In Vitro. 28 May 2020, 67:104903.
B. Warth, K. Preindl, P. Manser, P. Wick, D. Marko, T. Buerki-Thurnherr (2019). Transfer and metabolism of the xenostrogen zearalenone in human perfused placenta. Environ Health Persp., 127(10):107004.
A.H.C. Anthis, E. Tsolaki, L. Didierlaurent, S. Staubli, R. Zboray, A. Neels, D. Dietrich, P. Manser, L.M. Desbiolles, S. Leschka, S. Wildermuth, S. Lehner, P. Chavatte-Palmer, W. Jochum, P. Wick, A, Dommann, T. Bürki-Turnherr, T. Fischer, R. Hornung, S. Bertazzo, I.K. Herrmann (2019) Nano-analytical Characterization of Endogenous Minerals in Healthy Placental Tissue: Mineral Distribution, Composition and Ultrastructure, Analyst, 2019, DOI:10.1039/C9AN01312A
L. Aengenheister, BB. Dugershaw, P. Manser, A. Wichser, R. Schoenenberger, P. Wick, M. Hesler, Y. Kohl, S. Straskraba, MJF. Suter, T. Buerki-Thurnherr (2019). Investigating the accumulation and translocation of titanium dioxide nanoparticles wiith different surface modifications in static and dynamic human placental transfer models. Eur J Pharm Biopharm. 142:488-497
M. Hesler, L. Aengenheister, B. Ellinger, R. Drexel, S. Straskraba, C. Jost, S. Wagner, F. Meier, H. von Briesen, C. Büchel, P. Wick, T. Buerki-Thurnherr, Y. Kohl (2019). Multi-endpoint toxicological assessment of polystyrene nano- and microparticles in different biological models in vitro. Toxicol In Vitro. 2019 Jul 27;61:104610. DOI: 10.1016/j.tiv.2019.104610
B. Fadeel, C. Bussy, S. Merino, E. Vázquez, E. Flahaut, F. Mouchet, L. Evairste, L. Gauthier, J. Koivisto, U. Vogel, C. Martín, LG. Delogu, T. Buerki-Thurnherr, P. Wick, D. Beloin-Saint-Pierre, R. Hischier, M. Pelin, CF. Carniel, M. Tretiach, F. Cesca, F. Benfenati, D. Scaini, L. Ballerini, K. Kostarelos, M. Prato, A. Bianco (2018). Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano DOI: 10.1021/acsnano.8b04758
L. Aengenheister, D. Dietrich, A. Sadeghpour, P. Manser, L. Diener, A. Wichser, U. Karst, P. Wick, T. Buerki-Thurnherr (2018). Gold nanoparticle distribution in advanced in vitro and ex vivo human placental barrier models. J Nanobiotechnol (2018) 16:79.
T. Buerki-Thurnherr, K. Schaepper, L. Aengenheister, P. Wick (2018). Developmental toxicity of nanomaterials: Need for a better understanding of indirect effects. Chem. Res. Tox. 2018, 31 (8), 641-642.
T. Notter, L. Aengenheister, U. Stadlbauer-Weber, P. Wick, U. Meyer, T. Buerki-Thurnherr (2018). Prenatal exposure to TiO2 nanoparticles causes behavioral deficits relevant for autism-spectrum disorders and beyond. Transl. Psychiatry 2018 Sep 20;8(1):193.
M. Kucki, L. Aengenheister, L. Diener, A. Rippl, S. Vranic, L. Newman, E. Vazquez, K. Kostarelos, P. Wick, T. Buerki-Thurnherr (2018). Assessment of cell viability and functionality of human placental trophoblast cells in vitro after exposure to label-free graphene oxide. 2D Mater. 5, 035014
L. Aengenheister, K. Keevend, C. Muoth, R. Schönenberger, L. Diener, P. Wick, T. Buerki-Thurnherr (2018). An advanced human in vitro co-culture model for translocation studies across the human placental barrier. Sci Rep. 2018; 8 (1):5388
B. Drasler, M. Kucki, F. Delhaes, T. Buerki-Thurnherr, D. Vanhecke, D. Korejwo, A. Petri-Fink, B. Rothen-Rutishauser, P. Wick (2018). Single exposure to aerosolized graphene oxide and graphene nanoplatelets did not initiate an acute biological response in a 3D human lung model. Carbon, 137, 125-135
J. Vidmar, T. Buerki-Thurnherr, K. Loeschner (2018). Use of alkaline or enzymatic sample pre-treatment prior to characterization of silver nanoparticles in human tissue by single particle ICP-MS. J. Anal. At. Spectrom. 2018, 33, 752
M. Kucki, L. Diener, N. Bohmer, C. Hirsch, H.F. Krug, V. Palermo, P. Wick (2017). Uptake of label-free graphene oxide by Caco-2 cells is dependent on the cell differentiation status. J Nanobiotechology, 2017 Jun 21;15(1):46. doi: 10.1186/s12951-017-0280-7.
S. Chortarea, H. Barosova, MJD. Clift, P. Wick, A. Petri-Fink, B. Rothen-Rutishauser (2017). Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells. ACS Nano, 2017 May 23. doi: 10.1021/acsnano.7b01992.
C. Mouth, M. Grossgarten, U. Karst, J. A. Ruiz, D. Astruc, S. Moya, L. Diener, K. Grieder, A. Wichser, W. Jochum, P. Wick, T. Buerki-Thurnherr (2017). Impact of particle size and surface modification on the localization and penentration of gold nanoparticles in human placntal co-culture microtissues. Nanomedicine, 12(19), 1119-1133.
M. Kucki, P. Rupper, C. Sarrieu, M. Melucci, E. Treossi, A. Schwarz, V. León, A. Kraegeloh, E. Flahaut, E. Vázquez, V. Palermo, P. Wick (2016) Interaction of graphene-related materials with human intestinal cells: an in vitro approach. Nanoscale, 8(16):8749-60.
C. Muoth, M. Rottmar, A. Schipanski, C. Gmuender, K. Maniura-Weber, P. Wick, T. Buerki-Thurnherr. (2016) A micropatterning approach to study the influence of actin cytoskeletal organization on polystyrene nanoparticle uptake by BeWo cells. RSC Advances, 6, 72827-72835.
C. Mouth, L. Aengenheister, M. Kucki, P. Wick, T. Buerki-Thurnherr (2016). Nanoparticle transport across the placental barrier: pushing the field forward! Nanomedicine, 11(8), 941-57.
C. Muoth, A. Wichser, M. Monopoli, M. Correia, N. Ehrlich, K. Loeschner, A. Gallud, M. Kucki, L. Diener, P. Manser, W. Jochum, P. Wick, T. Buerki-Thurnherr (2016). A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment. Nanoscale, 8, 17322-17332.
S. Grafmueller, P. Manser, L. Diener, L. Maurizi, PA. Diener, H. Hofmann, W. Jochum, H.F. Krug, T. Buerki-Thurnherr, U. von Mandach, P. Wick (2015). Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts. Sci. Technol. Adv. Mater. 16 (4) 044602.
S. Grafmueller, P. Manser, L. Diener, PA. Diener, X. Maeder-Althaus, L. Maurizi, W. Jochum, H.F. Krug, T. Buerki-Thurnherr, U. von Mandach, P. Wick (2015). Differential bidirectional transfer of polystyrene nanoparticles across the placental barrier reveals different transport kinetics. Environ Health Persp., 123(12), 1280-6.
S. Grafmueller, P. Manser, H.F. Krug, P. Wick, U. von Mandach (2013). Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model. J. Vis. Exp., (76), e50401, doi:10.3791/50401.
T. Buerki-Thurnherr, U. von Mandach, P. Wick (2012). Knocking at the door of the unborn child: Engineered nanoparticles at the human placenta barrier. Swiss Med Wkly., 2012;142:w13559.
P. Wick, A. Malek, P. Manser, D. Meili, X. Maeder-Althaus, L. Diener, PA. Diener, A. Zisch, H.F. Krug, U. von Mandach(2010). Barrier capacity of human placenta for nanosized materials. Environ Health Perspect., 118(3):432-6. Epub 2009 Nov 12.
P. Wick, A. E. Louw-Gaume, M. Kucki, H. F. Krug, K. Kostarelos, B. Fadeel, K. A. Dawson, A. Salvati, E. Vazquez, L. Ballerini, M. Tretiach, F. Benfenati, E. Flahaut, L. Gauthier, M. Prato, and A. Bianco (2014). Classification Framework for Graphene-Based Materials. Angewandte Chemie Int. Ed., 53, 7714 – 7718.
New Papers online!
Best oral student presentation at Nanotox 2021 for Tuya. Well done!
Congrats Tuya for 2nd best poster award at SST 2019