NICe- Nanointercell

Research Activities

Team

Selected Publications

 

The Nano-Inter-Cell group performs cutting edge research at the interface of particles and cellular systems. Our ultimate goal is to provide the scientific understanding to steer the particles – cell interactions for a safe and efficient use.

Our motivation is to establish the knowledge of how engineered (nano)particles interact with human cells and tissue to identify opportunities and risks in early stage of development.

The interests of the group are situated at the interface of nanomaterials, biology, toxicology, in vitro technologies, bioanalytics and measurement science. We address fundamental and applied questions on nanoparticles uptake, accumulation and their biological response using human in vitro models. Furthermore we develop reliable and robust methods which enable a proper correlation of the physical-chemical properties of the nanomaterials with biological responses. Finally the scientific outcome of our research is made accessible for the society stimulating a fact-based and transparent safety debate.

How we serve to the COVID-19 crisis

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The SARS-CoV-2 virus, commonly known as COVID-19, demonstrated our inadequate response to a global pandemic and sparked the development of virus related research worldwide.
Our activities focus on three pillars: the research and development of novel antiviral surfaces and its analysis method, the toxicology assessment of protective safe mask debris and supporting of the analysis of the SARS-CoV-2 IgG and IgA antibody response from infected patients.

We collaborate with the other ETH domain institutions, mainly Ecole Polytechnique Fédérale de Lausanne (EPFL), Eidgenössische Technische Hochschule Zürich (ETHZ) and Labor Spiez, on the Innosuisse founded ReMask project.

Moreover, in a collaboration with the Center for Laboratory Medicine St. Gallen (ZLM), Our expertise is shared trough the data analysis of blood samples from a cohort study involving 159 COVID-19 positive patients. The data provides valuable insights on the change of antibodies and other biomarkers in positive and recovered patients, revealing key aspects of the human response to the infection by the virus.

Biological impact of nanomaterials

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Due to their novel properties, engineered nanoparticles hold many promises for technical as well as medical applications. However, exactly these novel properties raise concerns for the safe use and have led to a novel science field, the nanosafety research.

We have already successfully investigated numerous projects, while currently focusing on H2020 Flagship Graphene, SafeGraph part of the EU graphene Flagship. The aim is to continue to investigate the correlation of specific physico-chemical particle properties with their ability to evoked biological effect(s), while focusing on the understanding of protein adsorption patterns on nanoparticles, biotransformation, as well as the detection of cellular responses. In strong cooperation with our research partners we investigated in different types of nanomaterials, with well-defined properties such as metal and metal oxides, graphene related materials, carbon nanotubes and different polymer particles and we are ceaselessly motivated to keep exploring more materials.

 

Human cell based blood vessel – tissue barrier model to assess injectable nanoparticles

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Nanomedicines are applied mostly by injection, bypassing the classical lung, GI and skin barriers. Once in the blood stream the particles will be transported within the entire body until they were metabolized or secreted in the best case. In the meanwhile the can interact with blood component as well as the vessel – tissue barrier. The first interaction after injection triggers the bio-response and the fate of particles.

Leukocyte- endothelial interactions at sites of inflammation are one of the initial steps in vascular injury. Due to this important process, we established a co-culture model to study these interactions. Especially if nanoparticles are part of the system, the biological response and potentially harmful side effects may be clarified in advance. This also reduces the need for the use of animal models.

How in vitro data can be integrated into  LCIA

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With the growing application of nanomaterials in several sectors, there is increasing attention towards the identification and management of the potential risks along the product life cycle. Life Cycle Impact Assessment (LCIA) is a methodology that evaluates the magnitude of the environmental impacts of a product/service. The impacts on human health are calculated by extrapolating human effect factors  mainly from animal studies. Due to 3R and the push of alternative methods, in vivo data become scarcer, while in vitro data are increasing. However, in vitro data cannot be directly used in LCIA, and a standard integration strategy is missing. This represents a challenge especially for emerging technologies such as nanomaterials, because the lack of data results in the omission of potential impacts that, if known, could influence decision-making.

In the Horizon 2020 project Nanorigo, and in collaboration with ERAM and ALCA groups, we take the first steps towards the shift of Life Cycle Impact Assessment towards an in vitro-based assessment of nanomaterial impacts on human health. Our strategy for a quantitative in vitro-in vivo extrapolation takes into account both toxicodynamics and toxicokinetics aspects of nanomaterials, by integrating in vitro toxicity data and in silico models. As inhalation is considered the main route of exposure to nanomaterials, for example in the working environment, we put a particular focus on inhaled nanoparticles and their health effects.

Release of nanoparticles after mechanical treatments

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Nanomaterials are used e.g. as additives in paints, wood preservatives or to reinforce polymers. Despite the obvious benefits (e.g. obtaining a better protection of facades, reduced wood decay or improved mechanical properties of polymers) the potential hazard of these new products has to be assessed early in development.

In particular the release of nanoparticles either at the end of life or during mechanical abrasion needs to be explored in order to avoid social or economic drawbacks. Within H2020  Flagship Graphene  and SNSF 'Graphene at Lung' we estimated the potential release of nanomaterials during mechanical treatments of nanoparticles-containing paints, copper carbonate containing wood preservatives or carbon nanotubes as well as graphene reinforced polymers and assessed potential adverse effects of these processed materials. The addition of nanomaterials into paints or polymers did not lead to an additional ‘nano-risk’ due to a low amount of released particles and the absence of an acute cytotoxic response. However, the long-term consequences are still part of the ongoing research.

Reliable and robust characterization methods

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An important consideration in developing standards and regulations that govern the production and use of commercial nanoscale materials is the development of robust and reliable measurements to estimate with high confidence the physical-chemical properties as well as the potential adverse biological effects.

In the H2020 EU-NCL, SafeGraph and H2020 Refine project we developed protocols for nanoparticles size distribution, zeta potential measurement and in vitro assay (e.g. cell viability) within a global network (NIST, JRC, KRISS and Nanotech Thailand).

These concepts and protocols are published (see publications).

Knowledge Transfer

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We demonstrate our dedication to disseminate the latest know-how in the field of nanotechnology and safety, not just in the scientific community, but also to industry and society by taking the lead in the contactpointnano.ch project and being a part of the DaNa 2.0 network.

contactpointnano.ch is a national platform, pooling the scientific and regulatory knowledge and expertise available in Switzerland on the safe handling of synthetic nanomaterials (from production to use and disposal) and conveying it efficiently and in an understandable form to companies (start-ups, SMEs, and established firms). Contactpointnano.ch accelerates the knowledge transfer and eases the way from invention to innovation, through enabling access to nano experts in Switzerland, and gives access to thematic workshops, trainings and events, concomitantly to tailored advice and support.

Furthermore, we are part of DaNa 2.0 interdisciplinary team of experts from different research areas covering all aspects of nanosafety research (human and environmental toxicology, biology, physics, chemistry and pharmacy) working together to provide a web-based, non-biased, quality-approved and up-to-date knowledge base for more transparency.

For further information visit the contactpointnano.ch homage.

For further information visit the DaNa homepage.

H2020 Joint force project: GoNanoBioMat

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The aging population represents an enormous financial burden for society, unless ways can be found to maintain independence and quality-of-life (QoL) as long as possible for each individual. To achieve this, novel concepts and technologies for new solutions and products are needed. For example, the use of polymeric nanobiomaterials in medicine might be a solution for answering to this need.

Currently, the number of health applications on the market remains small due to the unclear situation of the future regulatory assessment of efficacy and safety. In this context, the GoBioNanoMat project aims to enable SMEs (small and medium size enterprises) and their suppliers, and Research Institutes to work on the development and production of polymeric nanobiomaterials for drug delivery implementing Safer-by-Design (SbD) approach. The major expected outcomes of this project are:

  1. A verified knowledge base (built on peer-reviewed scientific publications on polymeric nanobiomaterials, their environmental and human health risks and the regulatory aspects.),
  2. and guidelines to implement SbD approach for polymeric nanobiomaterial drug delivery systems
  3. as well as in depth investigation of three selected materials like Chitosan, Polylactic acid and Polyhydroxyalkanoates regarding drug delivery applications.

The GoNanoBioMat consortium combines expertise in the area of nanobiomaterial science and technology, life science, pharmaceutical science, as well as nanosafety and life cycle thinking. A strong regulatory background and knowledge base building, dissemination and training belong as well to the core competences of this consortium.

 

Team

Dr. Peter Wick, Head of Laboratory, Group Leader NICe

, +41 (0)58 765 76 84

Alma Mater: Uni Fribourg

Keywords: Nanoparticles, Nanomaterial characterization,  NanoSafety, Safe-by-Design, human in vitro models, assay reliability, nanomedicine 

 

Dr. Cordula Hirsch, Deputy Group Leader NICe

Alma Mater: Albert-Ludwigs-Universität Freiburg

Keywords: Cell biology, Primary cell culture, Nanosafety, In vitro assays

 

Dr. Nilda Vanesa Ayala Nunez, Scientist

Alma Mater: University of Groningen

Keywords: Nanosafety, in vitro endothelial models (mini-blood vessels), microfluidics

 

Dr.  Chrysovalanto Louka (Irene), Postdoc

Alma Mater: Swansea University and Universite Grenoble Alps

Keywords: ALI, in vitro (co)-cultures, skin, nanotoxicology, nanomaterials, Contactpointnano.ch

 

Pietro Clement, Scientist MSc

Alma Mater: École Polytechnique Fédérale de Lausanne (EPFL)

Keywords: Material science, antiviral characterization, fluorescence microscopy, nanoparticles, face-masks, surfaces and interfaces

 

Tobias Hoch, Scientist MSc

Alma Mater:

Keywords:

 

Philipp Meier, Scientist MSc

Alma Mater: Zurich University of Applied Sciences

Keywords: Cell biology, Protective Safe mask safety, In-vitro assays

 

Alexandra Rippl, Technical Expert

Keywords: Cell culture, Flow Cytometry, Confocal Microscopy, In vitro assays

 

Neda Iranpour Anaraki, shared PhD Student with lab 499 (xray facilities)

Keywords: Nanoparticles, Nano-bio Interactions, Nanoparticle Synthesis, Nanomaterials Characterization, Small Angle X-ray Scattering

 

Daina Romeo, PhD student

Keywords: Life Cycle Impact Assessment, nanotoxicology , inhalation, IVIVE

 

Alumni

 

Dr.  Niusha Nikravesh, Postdoc

Alma Mater: University of Birmingham

Keywords: Cell culture, Hydrogel delivery systems, Confocal microscopy, In vitro assays 

 

Dr. Ana Milosevic, Postdoc

Alma Mater: Uni Fribourg

Keywords: contactpointnano.ch

 

Liliane Diener, Technical Expert (biomedical scientist)

Keywords: Transmission Electron Microscope (TEM), biological sample preparation

 

Pauline Franz, MSc Student

Alma Mater: University of Constance

 

Dr. Juan Carlos Cassano, Postdoc

Alma Mater: University of Sydney

Keywords: Cell culture and Biology, Genotoxicity, Development of cancer diagnostic assays

 

Dr. Jean-Pierre Kaiser, Senior Scientist

Alma Mater: University of Zurich

Keywords: Nanotoxicology, Metallic nanoparticles, Microbiology, Cell biology, Endotoxin

 

Sarah May, PhD Student

Alma Mater: University of Constance

Keywords: Nanotoxicology, DNA damage, DNA repair pathways, In vitro assays

 

Saranya Muthusamy, MSc student

Alma Mater: TU Dresden

Keywords: Nanotechnology, Nanobiology

 

Dr. Nils Bohmer, Postdoc

Alma Mater: Freie Universität Berlin

Keywords: Cell culture, Nanomedicine, Endocytosis, Flow Cytometry

 

Biological impact of nanomaterials

 

Jesus S, Marques AP, Duarte A, Soares E, Costa JP, Colaco MA, Schmutz M, Som C, Borchard G, Wick P, Borges O (2020) Chitosan nanoparticles: shedding light on immunotoxicity and hemacompatibility, Front Bioeng Biotechnol 8;100

Hesler M, Aengenheister L, Ellinger B, Drexel R, Straskraba S, Jost CC, Meier F, Buechel C, Wick P, Bürki-Thurnherr T, Kohl Y, (2019) Multi-endpoint toxicological assessment of polystyrene nano- and micro- particles in different biological models in vitro, Toxicol in Vitro 61,104610

Ghaemi B, Moshiri A, Herrmann IK, Hajipour MJ, Wick P, Amani A, Sharmin Kharrazi (2019) Supramolecular insights into domino effect of Ag@ZnO-induced oxidative stress in melanoma cancer cells, ACS Applied Materials & Interfaces 11 (50), 46408-46418

Siegrist S, Cörek E, Detampel P, Sandström J, Wick P, Huwyler J, (2019) Preclinical Safety evaluation strategy for Nanomedicines, Nanotoxicology 13(1)73-99

Casalini T, Limongelli V, Schmutz M, Som C, Jordan O, Wick P, Borchard G, Perale G (2019) Molecular modeling for nanomaterials-biology interactiions: opportunities, challenges and perspectives, Front Bioeng Biotechnol 7,268

Jesus S, Schmutz M, Som C, Borchard G, Wick P, Borges O, (2019) Hazard assessment of polymeric nanobiomaterials for drug delivery: what can we learn from literature so far, Front Bioeng Biotechnol 7,261

Roman DL, Roman M, Som C, Schmutz M, Hernandez E, Wick P, Casaline T, Perale G, Ostafe V, Isvoran A, Computational assessment of the pharmacological profiles of degradation products of chitosan (2019) Front BioengBiotechnol 7,214

 

In vitro based LCIA

 

Romero D, Saleri B, Hischier R, Nowack B, Wick P, (2020) A potential integrated pathway for an early in vitro-based hazard assessment of nanoparticles Environ Intern 137;105505

Saleri B, Kaiser JP, Rösslein M, Hischier R, Nowack B, Wick P, (2020) Relative potency approach for using in vitro information for definition of effect factors of human toxicity in life cycle impact assessment Nanotoxicology. 14:2, 275-286

 

Release of nanoparticles after mechanical treatments

 

Netkueakul W, Korejwo D, Hammer T, Chortarea S, Rupper R, Braun O, Clamae M, Rothen-Rutishauser B, Buerki-Thurnherr T, Wang J*, Wick P*, (2020) Release of graphene-related materials from epoxy-based composites: characterization, quantification and hazard assessment in vitro (under revision NanoScale)

Civardi C, Grolimund D, Schubert M, Wick P, Schwarze FWMR, (2019) Micronized copper-treated wood: copper remobilization into spores from the copper-tolerant wood-destroying fungus Rhodonia placenta Environmental Science Nano 6(2),425-431

 

Reliable and robust characterization methods

 

Cassano JC, Rösslein M, Kaufmann R, Lüthi T, Schicht O, Wick P, Hirsch C, (2020) A novel approach to increase robustness, precision and high-throughput capacity of single cell gel electrophoresis, ALTEX 37(1);95-109

 

P. Franz, A. Bürkle, P. Wick, C. Hirsch (2020) Exploring flow cytometry-based micronucleus scoring for reliable nanomaterial genotoxicity assessment. Chemical Research in Toxicology 33: 2538-2549

 

Wick P, Franz P, Huber S, Hirsch C, (2020) Innovative Techniques and Strategies for a Reliable High-Throughput Genotoxicity Assessment, Chem. Res. Toxicol. 33, 2, 283-285

 

Petersen EJ, Hirsch C, Elliot JT, Wick P, Krug HF, Aengenheister L, May S, Rösslein M, et al., (2020) Cause–and-effect analysis as a tool to improve the reproducibility of Nanobioassays. Four case studies, Chem. Res. Toxicol. 33, 5, 1039-1054

 

Prina-Mello A, Schmid R, Wick P, Caputo F, Boisseau P, et al (2019) On the issue of transparency and reproducibility in nanomedicine, Nat Nanotech 14(7) 629-631

 

C. Hirsch and S. Schildknecht (2019) In vitro research reproducibility: keeping up high standards. Frontiers in Pharmacology, 10, 1484

 



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