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Pulmonary immune responses to biomedical nanoparticles and therapeutical applications

English title Pulmonary immune responses to biomedical nanoparticles and therapeutical applications
Applicant von Garnier Christophe
Number 122355
Funding scheme Project funding
Research institution Departement Magen-Darm-, Leber- und Lungenkrankheiten Universitätsspital Bern
Institution of higher education University of Berne - BE
Main discipline Immunology, Immunopathology
Start/End 01.03.2009 - 30.04.2012
Approved amount 288'000.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Biophysics

Keywords (5)

respiratory tract; immune response; pulmonary fibrosis; magnetic nanoparticles; particle surface

Lay Summary (English)

Lead
Lay summary
Lead: Utilisation of nanomaterials in medicine is the subject of intense research. The proposed project aims to understand how nanoparticles influence immune responses in the respiratory tract, and how biomedical particles can be applied for future novel diagnostic and therapeutic purposes.Background: Despite current intense research efforts in the development of biomedical nanomaterials, there is growing concern about their clinical applicability for therapeutic and diagnostic purposes, especially in the vulnerable respiratory tract environment. Though an important body of epidemiological and experimental research has addressed toxicological aspects of ambient nanoparticles, very few general trends have emerged that enable prediction of immune and inflammatory responses to a specific type and size of biomedical nanoparticle. Several reasons lie behind this lack of data, most importantly, physico-chemical nanoparticle properties, shell characteristics, and immunological effects have been incompletely investigated to date. Furthermore, a great deal of variability in the raw materials used and lack of standardised manufacturing processes have rendered the comparison between nanoparticles utilised by different research groups problematical. Prior to future application of biomedical nanoparticles within the respiratory tract, their interaction with resident immune and epithelial cells, post-exposure alterations of physico-chemical properties within the lung environment, and long-term consequences necessitate meticulous clarification.Aim: The proposed project aims to understand how inhaled and deposited biomedical nanoparticles influence immune responses in the respiratory tract, causing adverse health effects, and how nanocarriers can be applied for diagnostic and therapeutic purposes. Specially designed super-paramagnetic iron oxide nanoparticles will allow to monitor uptake in the lung and track interaction with the epithelial barrier and cells of the defence system, the macrophages and the dendritic cells.Expected value of the project: This multi-disciplinary project addresses essential shortcomings in our understanding of interactions between nanomaterials and the immune system in the respiratory tract. Lack of data in this area currently fuels public political debate about risks and benefits of nanomaterials, voicing concerns that stem from adverse health effects observed with combustion-derived particulate matter. Only a systematic, unbiased, and co-operative research approach uniting scientists, biologists, engineers, and clinicians will eventually succeed in providing a complete picture of how the respiratory tract immune system responds to nano-scale matter and is fundamental to develop biomedical nanoparticles for future therapeutic and diagnostic applications in the lung.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs) influences their oxidative and pro-inflammatory potential in vitro.
Gasser Michael, Wick Peter, Clift Martin Jd, Blank Fabian, Diener Liliane, Yan Bing, Gehr Peter, Krug Harald F, Rothen-Rutishauser Barbara (2012), Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs) influences their oxidative and pro-inflammatory potential in vitro., in Particle and fibre toxicology, 9(1), 17-17.
Biomedical nanoparticles modulate specific CD4+ T cell stimulation by inhibition of antigen processing in dendritic cells.
Blank Fabian, Gerber Peter, Rothen-Rutishauser Barbara, Sakulkhu Usawadee, Salaklang Jatuporn, De Peyer Karin, Gehr Peter, Nicod Laurent P, Hofmann Heinrich, Geiser Thomas, Petri-Fink Alke, Von Garnier Christophe (2011), Biomedical nanoparticles modulate specific CD4+ T cell stimulation by inhibition of antigen processing in dendritic cells., in Nanotoxicology, 5(4), 606-21.
Opportunities and challenges of the pulmonary route for vaccination.
Blank Fabian, Stumbles Philip, von Garnier Christophe (2011), Opportunities and challenges of the pulmonary route for vaccination., in Expert opinion on drug delivery, 8(5), 547-63.
Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall.
Blank Fabian, Wehrli Marc, Lehmann Andrea, Baum Oliver, Gehr Peter, von Garnier Christophe, Rothen-Rutishauser Barbara M (2011), Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall., in Immunobiology, 216(1-2), 86-95.
Immunology taught by lung dendritic cells.
von Garnier Christophe, Nicod Laurent P (2009), Immunology taught by lung dendritic cells., in Swiss medical weekly, 139(13-14), 186-92.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Size determines particle uptake efficiency and trafficking by prominent respiratory tract antigen presenting cell populations. Oral Presentation. Annual Meeting of the American Thoracic Society 2012 18.05.2012 San Francisco, USA
Nanocarrier size determines the respiratory tract antigen presenting cell population targeted. Annual meeting of the Swiss Society for Pulmonology 2012 25.04.2012 Crans-Montana, Switzerland
Investigating the influence of surface charge on the protein adsorption pattern and cellular interaction of polymer coated SPIONs in vitro. Oral presentation at Deutsche Forschungsgemeinschaft (Biological Responses to Nanoscale Particles) Workshop 2011 08.12.2011 Mainz, Germany
Different antigen presenting cell populations in the respiratory tract show size dependent particle uptake efficiency during steady state and allergic airways inflammation. Poster presentation. Annual Meeting of the European Respiratory Society 2011 24.09.2011 Amsterdam, Netherlands
Influence of surface charge on protein adsorption on polymer coated iron oxide nanoparticles. Poster presentation European Science Foundation Summer School 2011 19.06.2011 Berlin, Germany
Resident common precursors for dendritic cells and macrophages in the lung parenchyma. Poster Presentation. Annual Meeting of the American Thoracic Society 2011 13.05.2011 Denver, USA
Systemic distribution of biomedical nanoparticles applied via the pulmonary route. Poster presentation. Annual meeting of the Swiss Society for Pulmonology 2011 05.05.2011 Interlaken, Switzerland
Particle Size Determines Uptake Efficiency of Different Antigen Presenting Cell Populations in the Respiratory Tract During Steady State and Allergic Airways Inflammation. Oral presentation. Annual meeting of the Swiss Society for Pulmonology 2011 05.05.2011 Interlaken, Switzerland
Particle size determines uptake efficiency of different antigen presenting cell Populations in the respiratory tract during steady state and allergic airways inflammation. Poster presentation at the World Immune Regulation Meeting–V 2011 24.03.2011 Davos, Switzerland
Exposure of dendritic cells to biomedical nanoparticles decreases antigen processing capacity and specific CD4+ T cell stimulation. Poster presentation at the 11th International Symposium on Dendritic Cells in Fundamental and clinical Immunology 2010 04.10.2010 Lugano, Switzerland
Exposure of dendritic cells to biomedical nanoparticles decreases antigen processing capacity and specific CD4+ T cell stimulation. Poster presentation at the European respiratory Society Annual Conference 2010 18.09.2010 Barcelona, Spain
Surface charge and protein corona. Poster presentation at FriMat 2010 07.07.2010 Fribourg, Switzerland
Dendritic cells exposed to biomedical nanoparticles retain an immature like functional state and show reduced antigen specific CD4+ T cell stimulation in vitro. Poster presentation at the American Thoracic Society International Conference 2010 14.05.2010 New Orleans, USA
Exposure of dendritic cells to biomedical nanoparticles decreases antigen processing capacity and specific CD4+ T cell stimulation. Oral presentation at the annual meeting of the Swiss Society for Pulmonology 2010 16.04.2010 Lausanne, Switzerland
Biomedical nanoparticles decrease antigen-specific CD4+ T cell stimulation capacity of dendritic cells. Oral presentation. Pneumo Update Conference 2009 19.06.2009 Innsbruck, Austria


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Yin und Yang von Nanopartikeln in der Lunge. Veranstaltungsreihe Nanmedizin, Volkshochschule Bern German-speaking Switzerland 19.11.2011

Awards

Title Year
Bern University - Habilitation 2011
Swiss Society for Pulmonology 2011 - GlaxoSmithKline Award 2011
ERS Annual Inflammatory Airways Diseases and Clinical Allergy Award 2009
Top 5 Abstracts - Pneumo Update, Innsbruck, Austria 2009

Associated projects

Number Title Start Funding scheme
146249 Pulmonary immune responses to bio-mimetic antigen carriers for novel therapeutic approaches to treating allergic asthma 01.08.2013 Project funding
145003 A new Zeiss LSM 710 laser scanning microscope for the DCR LCI Core Facility 01.12.2012 R'EQUIP
128729 Nano-Optical processing and characterization of complex media for materials research and life sciences 01.01.2010 R'EQUIP

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