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 toxicity and translocation at biological barriers, in particular the human placenta. 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, 3D models or the recreation of a dynamic microenvironment. This research is supported by 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-placenta interactions
Increasing the 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 to treat the mother, the fetus or placental disorders with reduced off-target effects. We aim to obtain new mechanistic insights into particle-barrier interactions using our advanced placental models, extensive material knowhow and access to state-of-the art analytics. This research is supported by 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).
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. 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 (n°696656) 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
Alma Mater: University of Fribourg
Keywords: Realistic Nanosafety Assessment, Lung, Carbon Nanotubes, Gold Nanoparticles
Pius Manser, Technical Expert
Keywords: Ex vivo Placenta Perfusion, Nanotoxicology, Cell Biology
Leonie Aengenheister, PhD Student
Keywords: Advanced In Vitro models, Placenta, Nanoparticle Translocation
Claudia Hempt, PhD Student
Keywords: Advanced In Vitro Models, Nanotoxicology, Intestinal barrier
Daria Korejwo, PhD Student
Keywords: Nanosafety, Lung, Graphene
Dr. Melanie Kucki, Research Associate 2013-2017
Alma Mater: University of Kassel, Germany
Keywords: Graphene, Nanotoxicology, Intestine, Endotoxin
Carina Muoth, PhD Student 2013-2016
Alma Mater: University of Zurich
Keywords: 3D Microtissues, Placenta, Nanotoxicology, Primary Cell Culture
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.
This year's workshop was organized by our group and was a big success!