Project

Back to overview

Realistic exposure scenarios to study nanoparticle-lung cell interactions

English title Realistic exposure scenarios to study nanoparticle-lung cell interactions
Applicant Rothen-Rutishauser Barbara
Number 138365
Funding scheme Project funding
Research institution Adolphe Merkle Institute Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Cellular Biology, Cytology
Start/End 01.01.2012 - 30.09.2015
Approved amount 537'766.00
Show all

All Disciplines (3)

Discipline
Cellular Biology, Cytology
Environmental Research
Immunology, Immunopathology

Keywords (4)

Nanoparticles; Lung cell cultures; Chronic exposures; Co-exposures

Lay Summary (English)

Lead
Lay summary

Over the past decade, nanoparticles (NPs; diameter < 100nm) have been specifically manufactured, or engineered, for a diverse range of consumer, industrial and technological applications, such as medicine, cosmetics, environmental remediation and information technology. Due to the inevitable exposure of NPs to humans, owing to their use in such applications, it is thus imperative that an understanding as how NPs interact with the human body is gained and if potential adverse effects to humans have to be considered.

Although both epidemiologic and animal studies are used, most commonly, attempts regarding the investigation of potential adverse effects of inhaled combustion-derived and engineered NPs are performed using lung cell cultures in vitro. Such experimental studies are predominantly based upon the exposure of NPs in suspension; however, it has been recognized that the suspension scenario does not represent a realistic NP deposition as it occurs in the lung following their inhalation. Increased efforts have been made therefore, towards the use of sophisticated, dose-controlled NP exposure devices in combination with lung cell cultures at the air-liquid interface.

In the first part of the proposed project we aim to optimize our established and advanced 3D cell culture models of the airway and alveolar epithelial barrier to be cultured at the air-liquid interface for a prolonged period (several days to weeks). These cultures will then be used to address the questions about differences in chronic (i.e. repeated exposures as well as prolonged exposures), and acute NP exposure toxicity. In addition, co-exposure studies are planned in the second part of the project to evaluate the effects of two different NPs when combined. One important question will be if the combination of two (or more) different NPs elicits a synergistic effect compared to the effect observed from the exposure of each individual NP alone.

The aims of this proposal will be of great importance to gain new insights into the use of cell cultures to assess realistic exposure scenarios, (i.e. chronic exposures as well as co-exposures) since each situation is pertinent to the inevitable human interaction with accidental and engineered NPs.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
A biological perspective toward the interaction of theranostic nanoparticles with the bloodstream - what needs to be considered?
Clift Martin J D, Dechézelles Jean-François, Rothen-Rutishauser Barbara, Petri-Fink Alke (2015), A biological perspective toward the interaction of theranostic nanoparticles with the bloodstream - what needs to be considered?, Frontiers in Chemistry, Switzerland.
In vitro-ex vivo model systems for nanosafety assessment
Wick Peter, Chortarea Savvina, Guenat Olivier, Roesslein Matthias, Stucki Janick, Hirn Stephanie, Petri-Fink Alke, Rothen-Rutishauser Barbara (2015), In vitro-ex vivo model systems for nanosafety assessment, in European Journal of Nanomedicine , 7(3), 169-179.
Repeated exposure to carbon nanotube-based aerosols does not affect the functional properties of a 3D human epithelial airway model.
Chortarea Savvina, Clift Martin J D, Vanhecke Dimitri, Endes Carola, Wick Peter, Petri-Fink Alke, Rothen-Rutishauser Barbara (2015), Repeated exposure to carbon nanotube-based aerosols does not affect the functional properties of a 3D human epithelial airway model., in Nanotoxicology, 1-11.
Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages.
Kuhn Dagmar A, Vanhecke Dimitri, Michen Benjamin, Blank Fabian, Gehr Peter, Petri-Fink Alke, Rothen-Rutishauser Barbara (2014), Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages., in Beilstein journal of nanotechnology, 5, 1625-36.
Quantification of gold nanoparticle cell uptake under controlled biological conditions and adequate resolution.
Rothen-Rutishauser Barbara, Kuhn Dagmar A, Ali Zulqurnain, Gasser Michael, Amin Faheem, Parak Wolfgang J, Vanhecke Dimitri, Fink Alke, Gehr Peter, Brandenberger Christina (2014), Quantification of gold nanoparticle cell uptake under controlled biological conditions and adequate resolution., in Nanomedicine (London, England), 9(5), 607-21.
Quantification of nanoparticles at the single-cell level: an overview about state-of-the-art techniques and their limitations.
Vanhecke Dimitri, Rodriguez-Lorenzo Laura, Clift Martin J D, Blank Fabian, Petri-Fink Alke, Rothen-Rutishauser Barbara (2014), Quantification of nanoparticles at the single-cell level: an overview about state-of-the-art techniques and their limitations., in Nanomedicine (London, England), 9(12), 1885-900.
Bioavailability of silver nanoparticles and ions: from a chemical and biochemical perspective.
Behra Renata, Sigg Laura, Clift Martin J D, Herzog Fabian, Minghetti Matteo, Johnston Blair, Petri-Fink Alke, Rothen-Rutishauser Barbara (2013), Bioavailability of silver nanoparticles and ions: from a chemical and biochemical perspective., in Journal of the Royal Society, Interface / the Royal Society, 10(87), 20130396-20130396.
Nanomaterials and the human lung: what is known and what must be deciphered to realise their potential advantages?
Jud Corinne, Clift Martin J D, Petri-Fink Alke, Rothen-Rutishauser Barbara (2013), Nanomaterials and the human lung: what is known and what must be deciphered to realise their potential advantages?, in Swiss medical weekly, 143, 13758-13758.
Cerium dioxide nanoparticles can interfere with the associated cellular mechanistic response to diesel exhaust exposure
Steiner Sandro, Mueller Loretta, Popovicheva Olga B., Raemy David O., Czerwinski Jan, Comte Pierre, Mayer Andreas, Gehr Peter, Rothen-Rutishauser Barbara, Clift Martin J. D. (2012), Cerium dioxide nanoparticles can interfere with the associated cellular mechanistic response to diesel exhaust exposure, in TOXICOLOGY LETTERS, 214(2), 218-225.
Human epithelial cells in vitro – Are they an advantageous tool to help understand the nanomaterial-biological barrier interaction?
Rothen-Rutishauser Barbara, Clift Martin, Jud Corinne, Fink Alke, Wick Peter (2012), Human epithelial cells in vitro – Are they an advantageous tool to help understand the nanomaterial-biological barrier interaction?, in EuroNanoToxLetters, 4(1), 1-20.

Collaboration

Group / person Country
Types of collaboration
Prof. Wolfgang Parak/University of Marbug Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Harald Krug and Dr. Peter Wick/EMPA St. Gallen Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. J. Czerwinski/University of Applied Science Biel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Goldschmidt 2015 Talk given at a conference Risk assessment of inhaled airborne particles – clinical aspects and experimental designs 21.08.2015 Prag, Czech Republic Rothen-Rutishauser Barbara;
CLINAM 2015 Talk given at a conference Things you should be aware of when working with nanoparticles and cells 29.06.2015 Basel, Switzerland Rothen-Rutishauser Barbara; Petri-Fink Alke;
9. Int. Nano-Behördendialog – Block „Status Quo und Ausblick“ – Toxikologie Talk given at a conference Potential von Nanomaterialien – und welches sind die Risiken für den Menschen? 10.06.2015 Vaduz, Liechtenstein Rothen-Rutishauser Barbara;
20th conference of International Society of Aerosols in Medicine (ISAM), Talk given at a conference All about nanoparticles and lung cells 02.06.2015 Munich, Germany Rothen-Rutishauser Barbara;
International Congress on Safety of Engineered Nanoparticles and Nanotechnologies SENN2015 Talk given at a conference Opportunities and risks of nanomaterials - What can we learn by looking through a magnifying glas? 13.04.2015 Helsinki, Finland Rothen-Rutishauser Barbara;
PETA International Science Consortium, Ltd. Washington DC, USA - Workshop Talk given at a conference Design of an in vitro system to assess the inhalation toxicity of nanomaterials 24.02.2015 Washington, United States of America Rothen-Rutishauser Barbara;
BIOCOMBUST Meeting Talk given at a conference Feinstaub und Lunge - Klinische Aspekte und Aktuelles aus der Forschung 26.11.2014 Freiburg iBr, Germany Rothen-Rutishauser Barbara;
Lung Cell Biology, Imperial College - Seminar Individual talk Nanoparticles and lung cells – from risk assessment to biomedical applications 02.10.2014 London, Great Britain and Northern Ireland Rothen-Rutishauser Barbara;
9th World Congress on Alternatives in Animal Use in Life Sciences Talk given at a conference Next level in vitro testing strategy to study the effects of carbon nanotube aerosols 26.08.2014 Prag, Czech Republic Chortarea Savvina;
7th International Nanotoxicology Congress Talk given at a conference Nanoparticles and lung epithelial barriers – what we know and where to go from here”, 23.04.2014 Antalya, Turkey Rothen-Rutishauser Barbara;
Analytica 2014, Aerosol and Health: A challenge for chemical and biological analysis Talk given at a conference Combining 3D lung cultures and aerosol exposures at the air-liquid interface – a new generation of realistic risk assessment systems 01.04.2014 Munich, Germany Rothen-Rutishauser Barbara;
SPP1313 “Bio-Nano-Responses”, Fulda Talk given at a conference When Nanomaterials meet Cells – Towards a Fundamental Understanding of the Bio-Nano-Interface 03.03.2014 Fulda, Germany Rothen-Rutishauser Barbara;
Wissenschaftliche Grundlagen zur Regulation von Nanomaterialien, Oekotoxzentrum, Dübendorf Talk given at a conference Interaktion von Nanopartikeln mit biologischen Systemen 20.01.2014 Duebendorf, Switzerland Rothen-Rutishauser Barbara;
RBNI, Technion Seminar Series Individual talk 3D models of the human epithelial airway/alveolar barrier for risk assessment of inhaled nanomaterials 15.01.2014 Haifa, Israel Rothen-Rutishauser Barbara;
Institute of Food, Nutrition and Health Seminar Series Individual talk Nanomaterials and cells – pros and cons 10.12.2013 ETH Zuerich, Switzerland Rothen-Rutishauser Barbara;
Nanosafe 2013 Talk given at a conference Detection of nanomaterials at the single cell level – do and don’ts 21.11.2013 Saarbrücken, Germany, Germany Rothen-Rutishauser Barbara;
Fachhochschule Nordwestschweiz – Hochschule für Life Science Individual talk A 3D model of the human lung to mimic risk and opportunities of new inhalable drugs 21.10.2013 Muttenz, Switzerland Rothen-Rutishauser Barbara;
Novartis Seminar Individual talk The Bio-nano-interface – towards a fundamental understanding on how tailor-made nanomaterials interact with (lung) cells 09.09.2013 Basel, Switzerland Petri-Fink Alke; Rothen-Rutishauser Barbara;
Trends in Micro Nano – Swiss MNT Network Talk given at a conference Innovative Nanomaterialen - Risiken und Anwendungen 27.06.2013 Fribourg, Switzerland Rothen-Rutishauser Barbara;
6th CLINAM conference Talk given at a conference Novel Biomedical Nanocarriers for a Controlled Interaction with Cells 24.06.2013 Basel, Switzerland Rothen-Rutishauser Barbara;
CPC Grand Rounds Seminars Individual talk Going 3D with lung cell models – the next cell culture generation for risk assessment of inhaled xenobiotics 27.05.2013 Helmholtz Zentrum München, Deutschland, Germany Rothen-Rutishauser Barbara;
Jiao Tong University Shanghai Individual talk Design of safe nanomaterials – From concept to application! 08.05.2013 Shanghai, China Rothen-Rutishauser Barbara; Petri-Fink Alke;
Pharmazie Kolloquium Universität Freiburg Individual talk Sophisticated lung cell models combined with air-liquid exposures to (nano)particles – a new tool for the risk assessment of inhaled xenobiotics 16.04.2013 Freiburg iBr, Germany Rothen-Rutishauser Barbara;
19th ISAM Conference Talk given at a conference Nanoparticle Exposure of in vitro Epithelial Co-culture Cell Systems for Risk Assessment 06.04.2013 Chapel Hill, North Carolina, United States of America Rothen-Rutishauser Barbara;
TEDD workshop Talk given at a conference A 3D model of the human epithelial airway barrier – are we already done? 14.03.2013 St. Gallen, Switzerland Rothen-Rutishauser Barbara;
Risk assessment of inhaled (nano)particles using an advanced 3D model of the human lung Individual talk Swiss Tropical and Public Health Institute Seminar Series 28.02.2013 Basel, Switzerland Rothen-Rutishauser Barbara;
Universität Salzburg Seminar Series Individual talk Nano and the lung – good or bad? 14.01.2013 Salzburg, Austria Rothen-Rutishauser Barbara;
Kolloquium “Life Sciences and Facility Management, Zurich University of Applied Sciences”, Waedenswil, Switzerland Talk given at a conference Interactions of inhaled biomedical (nano)materials with cells using an advanced 3D model of the human lung 12.11.2012 Waedenswil, Switzerland Rothen-Rutishauser Barbara; Petri-Fink Alke;
NanoFormulation 2012 Talk given at a conference Design of safe nanomaterials - What cells can tell us! 28.05.2012 Barcelona, Spain Rothen-Rutishauser Barbara;


Self-organised

Title Date Place
TEDD-Workshop: Models of the Respiratory Tract and their Application 22.01.2015 Adolphe Merkle Institute, University of Fribourg, Switzerland
Swiss Aerosol Group - 9th Meeting 10.11.2014 Bern, Switzerland
Swiss Aerosol Group - 8th Meeting 18.11.2013 Bern, Switzerland
Swiss Aerosol Group - 7th Meeting 20.11.2012 Bern, Switzerland

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Chancen und Risiken von Nanomaterialien Talk 29.11.2014 Adolphe Merkle Institute, Fribourg - Open door day, Switzerland Rothen-Rutishauser Barbara;
Nanotechnologie - Nutzen und Risiken Performances, exhibitions (e.g. for education institutions) 19.11.2013 Gymnasium Thun -Schadau, Switzerland Rothen-Rutishauser Barbara;
Nanotechnologie – Nutzen und Risiken Performances, exhibitions (e.g. for education institutions) 30.08.2012 Gymnasium Muenchenstein, Basel, Switzerland Rothen-Rutishauser Barbara;
Luft ohne Schadstoffe! Klinische Folgen – Biologische Mechanismen Talk 14.06.2012 Aerztinnen und Aerzte für Umweltschutz, Luzern, Switzerland Rothen-Rutishauser Barbara;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Kleine Zwerge ganz gross: Faszinierende Einblicke in die Nano­welt German-speaking Switzerland 2014
Talks/events/exhibitions Women in Science Western Switzerland 2012

Awards

Title Year
PETA International Science Consotrium Ltd. Award 2015 for the development of an in vitro lung test to predict the toxicity of inhaled nanomaterials 2015
Prix Fond Carlo de La Fondation Philanthropia 2015
Young Scientist Travel Award (YSTA) to participate in the 19th European Congress on Alternatives to Animal Testing – Linz 2015/EUSAAT 2015 in Linz, Austria, from 20 to 23 September 2015 2015
Egon Naef Prize 2014 for research on in vitro alternative methods 2014
2nd prize from the Ypsomed Innovation Fund for Research and Development 2012

Associated projects

Number Title Start Funding scheme
159847 Towards a fundamental understanding of nanoparticle exocytosis from cells 01.10.2015 Project funding
123373 Advances in Nanoparticle Engineering with a focus on Stability, Surface, and Particle-Cell Interaction 01.10.2009 SNSF Professorships
118420 Interplay of lung cells and their cellular responses upon exposure to combustion-generated ultrafine particles and manufactured nanoparticles 01.10.2007 Project funding
157752 Microchip-based flow cell sorting in biomedicine and material sciences 01.05.2015 R'EQUIP
131266 Biomedical nanoparticles as immune-modulators 01.05.2011 NRP 64 Opportunities and Risks of Nanomaterials
156871 Understanding the interaction of nanoparticles with B lymphocytes in vitro and in vivo 01.02.2015 Project funding

Abstract

Despite the many proposed advantages related to nanotechnology, there are increasing concerns as to the potential adverse human health and environmental effects that the production of, and subsequent exposure to nanotechnology related products might pose. In regards to human health, these concerns are founded upon the plethora of knowledge gained from research relating to the effects observed following exposure to environmental air pollution. With the ever increasing nanotechnology industry, it is not however, simply exposure to accidentally, mainly by combustion processes, produced nanoparticles (NPs) which should be approached with caution. Over the past decade, NPs have been specifically manufactured, or engineered, for a diverse range of consumer, industrial and technological applications, such as medicine, cosmetics, environmental remediation and information technology. Due to the inevitable exposure of NPs to humans, owing to their use in such applications, it is thus imperative that an understanding as how NPs interact with the human body is gained.Although both epidemiologic and animal studies are used, most commonly, attempts regarding the investigation of potential adverse effects of inhaled combustion-derived and engineered NPs are performed using lung cell cultures in vitro. Such experimental studies are predominantly based upon the exposure of NPs in suspension; however, it has been recognized during the last years that components in the media, such as serum and other proteins might lead to a change in NP agglomeration/aggregation status and thus a change of their surface properties (i.e. by the binding of proteins to the NP surface). In addition, the suspension scenario does not represent a realistic NP deposition as it occurs in the lung following their inhalation. Increased efforts have been made therefore, towards the use of sophisticated, dose-controlled NP exposure devices in combination with lung cell cultures at the air-liquid interface. However, so far, such studies have only considered acute exposures (i.e. a single exposure of NPs). In the first part of the proposed project (Section 2.3.A) (Work-package 1) we aim to optimize our established and advanced 3D cell culture models of the airway and alveolar epithelial barrier to be cultured at the air-liquid interface for a prolonged period (several days to weeks). These cultures will then be used to address the questions about differences in chronic (i.e. repeated exposures as well as prolonged exposures), and acute NP exposure toxicity. In addition, co-exposure studies are planned in the second part of the project (Section 2.3.B) (Work-package 2) to evaluate the effects of two different NPs when combined. One important question will be if the combination of two (or more) different NPs elicits a synergistic effect compared to the effect observed from the exposure of each individual NP alone. In addition, the susceptibility of lung cell cultures pre-exposed to diesel exhaust followed by exposure to engineered NPs will be studied. The aims of this proposal will be of great importance to gain new insights into the use of cell cultures to assess realistic exposure scenarios, (i.e. chronic exposures as well as co-exposures) since each situation is pertinent to the inevitable human interaction with accidental and engineered NPs.
-