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Towards a fundamental understanding of nanoparticle exocytosis from cells

English title Towards a fundamental understanding of nanoparticle exocytosis from cells
Applicant Rothen-Rutishauser Barbara
Number 159847
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 01.10.2015 - 31.01.2019
Approved amount 598'566.00
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All Disciplines (3)

Discipline
Cellular Biology, Cytology
Immunology, Immunopathology
Pharmacology, Pharmacy

Keywords (6)

Exocytosis; Air-blood tissue barrier; Translocation; Nanoparticles; Degradation; Nanoparticle transfer

Lay Summary (German)

Lead
Das Verständnis der Interaktion von künstlichen Nanopartikeln mit zellulären Systemen ist Voraussetzung für die sichere Anwendung von innovativen Materialien im Bereich Nanotechnologie und Medizin. Die meisten Studien fokussieren heute auf die zellulären Aufnahmemechanismen von Nanopartikeln, deren intrazelluläre Verteilung sowie mögliche zelluläre Reaktionen. Im Gegensatz dazu ist nur wenig über die mögliche Freisetzung (Exozytose) von Nanopartikeln bekannt.
Lay summary

Inhalt und Ziele des Forschungsprojekts

Ziel dieses Projektes ist es die zelluläre Freisetzung von Nanopartikeln zu untersuchen und wie dieser Prozess von Faktoren wie Grösse, Material und Oberfläche der Partikel aber auch vom Zelltyp beeinflusst wird. Mit unserer interdisziplinären Expertise werden wir die Verteilung innerhalb der Zelle und die Freisetzung von definierten Nanopartikeln nach deren Aufnahmen mit einer Kombination an analytischen Methoden und Mikroskopie-Techniken untersuchen.

Ausserdem werden wir das Zusammenspiel von Zellen, also die mögliche Übergabe von Nanopartikeln von einer Zelle auf eine zweite Zelle, untersuchen. In einem weiteren Schritt simulieren wir die Inhalation von Partikeln mit einem komplexen 3D Zellkulturmodell der Luftwegsepithelialwand mit einer Exposition von Nanopartikeln an der Luftflüssigkeitsgrenze. Die Untersuchung der Aufnahme der Nanopartikel in bestimmte Abwehrzellen wie Makrophagen oder dendritische Zellen sowie der Transport über die Luftwegsepithelialwand sind weitere Ziele dieses Projektes.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojektes

Mit einem grundlegenden Verständnis der Interaktion von Nanopartikel mit Zellen – wie die Aufnahme, Degradation, Ausscheidung, Übergabe an andere Zellen oder den Transport über die Luft-Blut-Schranke – können wir einen wichtigen Beitrag zur sicheren Entwicklung von Nanopartikeln für diverse Anwendungen wie in der Medizin leisten.

Direct link to Lay Summary Last update: 29.03.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Rapid and sensitive quantification of cell-associated multi-walled carbon nanotubes
Steinmetz Lukas, Bourquin Joel, Barosova Hana, Haeni Laetitia, Caldwell Jessica, Milosevic Ana, Geers Christoph, Bonmarin Mathias, Taladriz-Blanco Patricia, Rothen-Rutishauser Barbara, Petri-Fink Alke (2020), Rapid and sensitive quantification of cell-associated multi-walled carbon nanotubes, in Nanoscale, 12(33), 17362-17372.
Reduction of Nanoparticle Load in Cells by Mitosis but Not Exocytosis
Bourquin Joël, Septiadi Dedy, Vanhecke Dimitri, Balog Sandor, Steinmetz Lukas, Spuch-Calvar Miguel, Taladriz-Blanco Patricia, Petri-Fink Alke, Rothen-Rutishauser Barbara (2019), Reduction of Nanoparticle Load in Cells by Mitosis but Not Exocytosis, in ACS Nano, 13(7), 7759-7770.
Artificial lysosomal platform to study nanoparticle long-term stability
Milosevic Ana, Bourquin Joel, Burnand David, Lemal Philipp, Crippa Federica, Monnier Christophe, Rodriguez-Lorenzo Laura, Petri-Fink Alke, Rothen-Rutishauser Barbara (2019), Artificial lysosomal platform to study nanoparticle long-term stability, in Chimia, 55-58.
Emergence of nanoplastic in the environment and possible impact on human health
Lehner Roman, Weder Christoph, Petri-Fink Alke, Rothen-Rutishauser Barbara (2019), Emergence of nanoplastic in the environment and possible impact on human health, in Environ. Sci. Technol., 1.
Nanoparticle-cell interactions – Overview about uptake, intracellular fate and induction of cell responses
Rothen-Rutishauser Barbara, Bourquin Joel, Alke Petri-Fink (2019), Nanoparticle-cell interactions – Overview about uptake, intracellular fate and induction of cell responses, in Zellner Reinhard, Gehr Peter (ed.), Springer Nature, Heidelberg, Chapter 6.
The crux of positive controls - Pro-inflammatory responses in lung cell models
Bisig Christoph, Voss Carola, Petri-Fink Alke, Rothen-Rutishauser Barbara (2019), The crux of positive controls - Pro-inflammatory responses in lung cell models, in Toxicology in Vitro, 54, 189-193.
A novel sample holder for 4D live cell imaging to study cellular dynamics in complex 3D tissue cultures
Septiadi D., Bourquin J., Durantie E., Petri-Fink A., Rothen-Rutishauser B. (2018), A novel sample holder for 4D live cell imaging to study cellular dynamics in complex 3D tissue cultures, in Sci Rep., 8(1), 9861.
Biodistribution, Clearance, and Long-Term Fate of Clinically Relevant Nanomaterials
Bourquin Joël, Milosevic Ana, Hauser Daniel, Lehner Roman, Blank Fabian, Petri-Fink Alke, Rothen-Rutishauser Barbara (2018), Biodistribution, Clearance, and Long-Term Fate of Clinically Relevant Nanomaterials, in Advanced Materials, 1704307-1704307.
Distribution of polymer-coated gold nanoparticles in a 3D lung model and indication of apoptosis after repeated exposure
Chortarea Savvina, Fytianos Kleanthis, Rodriguez-Lorenzo Laura, Petri-Fink Alke, Rothen-Rutishauser Barbara (2018), Distribution of polymer-coated gold nanoparticles in a 3D lung model and indication of apoptosis after repeated exposure, in Nanomedicine, 13(10), 1169-1185.
Profibrotic Activity of Multiwalled Carbon Nanotubes Upon Prolonged Exposures in Different Human Lung Cell Types
Chortarea Savvina, Zerimariam Fikad, Barosova Hana, Septiadi Dedy, Clift Martin J.D., Petri-Fink Alke, Rothen-Rutishauser Barbara (2018), Profibrotic Activity of Multiwalled Carbon Nanotubes Upon Prolonged Exposures in Different Human Lung Cell Types, in Applied In Vitro Toxicology, 1.
A novel technique to determine the cell type specific response within an in vitro co-culture model via multi-colour flow cytometry
Clift Martin J. D., Fytianos Kleanthis, Vanhecke Dimitri, Hočevar Sandra, Petri-Fink Alke, Rothen-Rutishauser Barbara (2017), A novel technique to determine the cell type specific response within an in vitro co-culture model via multi-colour flow cytometry, in Scientific Reports, 7(1), 434-434.
Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model
Fytianos Kleanthis, Chortarea Savvina, Rodriguez-Lorenzo Laura, Blank Fabian, von Garnier Christophe, Petri-Fink Alke, Rothen-Rutishauser Barbara (2017), Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model, in ACS Nano, 11(1), 375-383.
Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface
Durantie Estelle, Vanhecke Dimitri, Rodriguez-Lorenzo Laura, Delhaes Flavien, Balog Sandor, Septiadi Dedy, Bourquin Joel, Petri-Fink Alke, Rothen-Rutishauser Barbara (2017), Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface, in Particle and Fibre Toxicology, 14(1), 49.
Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells
Chortarea Savvina, Barosova Hana, Clift Martin James David, Wick Peter, Petri-Fink Alke, Rothen-Rutishauser Barbara (2017), Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells, in ACS Nano, 11(8), 7615-7625.
In vitro approaches to assess the hazard of nanomaterials
Drasler Barbara, Sayre Phil, Steinhäuser Klaus Günter, Petri-Fink Alke, Rothen-Rutishauser Barbara (2017), In vitro approaches to assess the hazard of nanomaterials, in NanoImpact, 0, 51.
Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages
Vanhecke Dimitri, Kuhn Dagmar A., Aberasturi Dorleta Jimenez de, Balog Sandor, Milosevic Ana, Urban Dominic, Peckys Diana, Jonge Niels de, Parak Wolfgang J., Petri-Fink Alke, Rothen-Rutishauser Barbara (2017), Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages, in Beilstein Journal of Nanotechnology, 8(1), 2396-2409.
Quantifying nanoparticle cellular uptake: which method is best?
DraslerBarbara, VanheckeDimitri, Rodriguez-LorenzoLaura, Petri-FinkAlke, Rothen-RutishauserBarbara (2017), Quantifying nanoparticle cellular uptake: which method is best?, in Nanomedicine, 12(10), 1095.

Collaboration

Group / person Country
Types of collaboration
Prof. Albert Duschl / University of Salzburg Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Christoph Weder/Adolph Merkle Institute Fribourg Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Dr. Christophe von Garnier/Pneumology Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. O Schmid/Helmholtz Centre Munich Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. J. Czerwinski/University of Applied Science Biel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Dr. Fabian Blank/Pneumologie Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Wolfgang Parak/University of Marbug Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Mini-Symposium LabEx CSC - Chemistry meets Medicine Talk given at a conference Nanoparticle-cell interactions – what we know and where to go from here 13.12.2018 Strasbourg, France Rothen-Rutishauser Barbara;
AMI Seminar, University Fribourg Individual talk Long-term fate of silica and gold nanoparticles in macrophages in vitro 27.11.2018 Fribourg, Switzerland Bourquin Joël;
20th International Congress on In Vitro Toxicology Talk given at a conference Predictive 3D lung models to assess the hazard of inhaled nanomaterials 18.10.2018 Berlin, Germany Rothen-Rutishauser Barbara;
9th Nanotox Conference Poster Silica nanoparticles are retained in macrophages 18.09.2018 Neuss, Germany Bourquin Joël;
CLINAM 2018 Talk given at a conference The Behavior of Nanoparticles in Complex Environments 03.09.2018 Basel, Switzerland Rothen-Rutishauser Barbara; Petri-Fink Alke;
LIVe 2018 Talk given at a conference Human lung cell co-cultures 05.07.2018 Nice, France Rothen-Rutishauser Barbara;
BTS Congress 2018 Talk given at a conference In vitro systems to study the toxicology of particles and drugs at the epithelial lung tissue barrier 17.04.2018 Newcastle, Great Britain and Northern Ireland Rothen-Rutishauser Barbara;
Society of Toxicology 57th meeting Talk given at a conference Predictive 3D lung models to assess the toxicity of inhaled nanoparticles 12.03.2018 San Antonio, Texas, United States of America Rothen-Rutishauser Barbara;
Society of Toxicology Contemporary Concepts in Toxicology Meeting Talk given at a conference Using Organotypic Airway Models to Study the Biological Effects of Aerosols 10.03.2018 San Antonio, Texas, United States of America Rothen-Rutishauser Barbara;
Farewell Symposium Prof. Harald Krug - Health Implications of Technical Developments Talk given at a conference Nanoparticles and the lung – should we be worried? 21.09.2017 St. Gallen, Switzerland Rothen-Rutishauser Barbara;
21st ISAM Conference Talk given at a conference Lung Tissue Engineering by a Bioprinting Approach – Opportunities and Challenges 05.06.2017 Santa Fe, NM, United States of America Rothen-Rutishauser Barbara;
CLINAM 2017 Talk given at a conference “Nanoparticle Delivery to Immune Cells in the Lung – From Complex 3D Lung Models to in Vivo Experiments” 10.05.2017 Basel, Switzerland Rothen-Rutishauser Barbara;
CLINAM 2016, Basel, Switzerland Talk given at a conference Quantification of nanoparticles at the single cell level using microscopic and analytical techniques 27.06.2016 Basel, Switzerland Rothen-Rutishauser Barbara;
20th ETH-Conference on Combustion Generated Nanoparticles, ETH Zuerich, Switzerland Talk given at a conference Differentiating the mechanism of lung cell interactions between diesel exhaust particles and carbonaceous fibrous structures 15.06.2016 Zürich, Switzerland Rothen-Rutishauser Barbara;
8th Nanotox Conference Talk given at a conference Biological impact of sub-chronic repeated exposures to aerosolised MWCNTs on healthy and asthmatic lung cells at occupational relevant doses 02.06.2016 Boston, United States of America Chortarea Savvina;
Biomedical Engineering Day 2016, University of Bern, Bern, Switzerland Talk given at a conference Nanomaterials for life sciences – opportunities and challenges 27.05.2016 Bern, Switzerland Rothen-Rutishauser Barbara;
Designing biomedical nanocarriers for a controlled interaction with immune cells in the lung Talk given at a conference i-Net Nanotechnology Event 21.01.2016 Basel, Switzerland Rothen-Rutishauser Barbara;


Self-organised

Title Date Place
Swiss Aerosol Group - 13th Meeting 05.11.2018 Bern, Switzerland
Swiss Aerosol Group - 12th Meeting 13.11.2017 Bern, Switzerland
Swiss Aerosol Group -11th Meeting 14.11.2016 Bern, Switzerland
Swiss Nanoconvention 2017 01.06.2016 Fribourg, Switzerland
Swiss Aerosol Group - 10th Meeting 02.10.2015 Bern, Switzerland

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Chancen und Risiken von Nanomaterialien Western Switzerland 2018
Media relations: print media, online media Königin der Kleinstteile Bilanz 04/2017 German-speaking Switzerland 2017
Talks/events/exhibitions Nanomedizin – Neue Ansätze, Wirkstoffe, Therapien und Verfahren – Stand der Forschung German-speaking Switzerland 2017
Talks/events/exhibitions Nationale Anlaufstelle “Nano-KMU” German-speaking Switzerland 2017

Awards

Title Year
Prix CUSSTR 2017 awarded to A. Groso (EPFL), T. Meyer(EPFL), H. Hofmann, A. Fink (UniFR) and B. Rothen-Rutishauser (UniFR) for the work “Engineered nanomaterials – toward effective safety management in research laboratories” 2017
2nd best oral presentation award, 8th Nanotox Conference, Boston, USA 2016
Young Investigator Award, 8th Nanotox Conference, Boston, USA 2016
PETA International Science Consotrium Ltd. Award 2015 for the development of an in vitro lung test to predict the toxicity of inhaled nanomaterials 2015
Young Scientists award, 19th European Congress on Alternatives to Animal Testing, Linz, Austria 2015

Associated projects

Number Title Start Funding scheme
138365 Realistic exposure scenarios to study nanoparticle-lung cell interactions 01.01.2012 Project funding
131266 Biomedical nanoparticles as immune-modulators 01.05.2011 NRP 64 Opportunities and Risks of Nanomaterials
141849 NCCR Bio-Inspired Materials: Center for Bio-Inspired Stimuli-Responsive Materials (phase I) 01.06.2014 National Centres of Competence in Research (NCCRs)
192056 Long-term fate of internalized nanoparticles in macrophages 01.09.2020 Project funding
146249 Pulmonary immune responses to bio-mimetic antigen carriers for novel therapeutic approaches to treating allergic asthma 01.08.2013 Project funding

Abstract

The great potential of nanoparticles (NPs) for diagnostic and therapeutic applications requires a thorough understanding on how these particles interact with single cells. There is convincing evidence that, depending on the physico-chemical properties of NPs, cells take up NPs via various endocytotic uptake mechanisms. However, possible subsequent release and degradation of the particles, and / or if they are transferred to other cells is still unknown, but the involvement of these cellular clearance mechanisms will strongly influence the efficacy of NPs used for imaging contrast or drug delivery and we therefore need to understand them.To address this issue we will investigate the fate of various NPs after endocytosis using an interdisciplinary approach combining controlled material design and single cells cultured under defined conditions by cutting-edge methods used in nanoscience such as analytical and imaging techniques. Since the inhalation route of NPs delivered into the lungs is promising we also aim to apply a more complex 3D lung system to study the biokinetics and possible clearance of NPs deposited onto the lung cell surface.The project is divided into three work-packages (WP) - all of them studying the possible exocytosis of NPs after uptake. WP1 focuses on how NP properties such as size, surface, and material influence release and degradation in single cells. In addition, other factors that might influence exocytosis such as cell type, differentiation state, and species will be studied. The transfer of NPs from one cell type to another one is in the focus of WP2. Finally, we will use a well-established air-liquid interface cell exposure system to study the translocation of NPs across the tissue barrier of the human lung epithelium (WP3). The system allows dose-controlled delivery of NPs and subsequent determination of the particle fate within different fractions, i.e. unbound on the apical lung cell surface, within cells, and in the medium in the lower compartment. With this project we will discover if the NP properties influence a possible exocytosis by various cells and / or translocation across a human lung epithelial tissue barrier and if the manipulation of NP properties can control these clearance processes. Our results will provide a more complete understanding of the behavior of NPs at the (lung) cell biointerface. This knowledge will allow us to develop new (inhalative) NPs in order to take advantage of nanotechnology applications in biotechnology and in medicine.
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