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Biomedical nanoparticles as immune-modulators

English title Biomedical nanoparticles as immune-modulators
Applicant Rothen-Rutishauser Barbara
Number 131266
Funding scheme NRP 64 Opportunities and Risks of Nanomaterials
Research institution Adolphe Merkle Institute Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Immunology, Immunopathology
Start/End 01.05.2011 - 30.11.2015
Approved amount 869'687.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Cellular Biology, Cytology

Keywords (3)

Nanoparticles; Lung cells; Immune-modulation

Lay Summary (English)

Lead
Lay summary
The aetiology of allergic asthma is multi-factorial and triggered by a skewed immune response to innocuous airborne allergens such as dust mite allergen and pollen. Despite intense research, rates of allergy and allergy-induced asthma continue to rise in most industrialised nations and also in emerging countries. Nanoparticles (NP) synthesised by nanotechnology may have many different shapes and chemical compositions, therefore their properties can be specifically designed for clinical diagnostic and therapeutic applications. Recent studies have shown that NP can stimulate or suppress various immune response pathways; however the effects of NP on the immune system in relation to the particle properties (size, surface modification, solubility and shape) are unknown to date.In order to harness the unique properties of NP for novel clinical applications in the treatment of allergic respiratory disease, we propose to develop and utilise specifically designed NP to investigate immune-modulatory and anti-inflammatory effects in the lung with various experimental approaches: (I) In vitro systems of the human lung to evaluate the trafficking of NP by macrophages (innate immune system) and dendritic cells (adaptive immune system), as well as their potentially associated immune-modulatory effects and nano-immunotoxicity.(II) In vivo assays, i.e. allergic respiratory disease models, to evaluate the immune-modulatory potential of NP and adverse nano-immunotoxic effects.The aim of the proposed project is to specifically evaluate designed NP as pulmonary anti-allergic nanovaccines for the treatment of allergic asthma by utilising established methods to investigate immune-modulatory effects and study possible associated health risks such as nano-immunotoxicity.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Interaction of biomedical nanoparticles with the pulmonary immune system.
Blank Fabian, Fytianos Kleanthis, Seydoux Emilie, Rodriguez-Lorenzo Laura, Petri-Fink Alke, von Garnier Christophe, Rothen-Rutishauser Barbara (2017), Interaction of biomedical nanoparticles with the pulmonary immune system., in Journal of Nanobiotechnology, 15(6), 1-9.
Current in vitro approaches to assess nanoparticle interactions with lung cells.
Fytianos Kleanthis, Drasler Barbara, Blank Fabian, von Garnier Christophe, Seydoux Emilie, Rodriguez-Lorenzo Laura, Petri-Fink Alke, Rothen-Rutishauser Barbara (2016), Current in vitro approaches to assess nanoparticle interactions with lung cells., in Nanomedicine (Lond). , 11(18), 2457-2469.
Pulmonary delivery of cationic gold nanoparticles boost antigen-specific CD4(+) T Cell Proliferation.
Seydoux Emilie, Rodriguez-Lorenzo Laura, Blom Rebecca A M, Stumbles Philip A, Petri-Fink Alke, Rothen-Rutishauser Barbara M, Blank Fabian, von Garnier Christophe (2016), Pulmonary delivery of cationic gold nanoparticles boost antigen-specific CD4(+) T Cell Proliferation., in Nanomedicine : nanotechnology, biology, and medicine, 12(7), 1815-1826.
In vitro-ex vivo model systems for nanosafety assessment
Peter Wick, Savvina Chortarea, Olivier Guenat, Matthias Roesslein, Janick Stucki, Alke Petri-Fink, Barbara Rothen-Rutishauser (2015), In vitro-ex vivo model systems for nanosafety assessment, in Eur J Nanomed , 7(3), 169-179.
Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro
Fytianos Kleanthis, Rodriguez-Lorenzo Laura, Clift Martin J. D., Blank Fabian, Vanhecke Dimitri, von Garnier Christophe, Petri-Fink Alke, Rothen-Rutishauser Barbara (2015), Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro, in NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 11(3), 633-644.
Advanced human in vitro models to assess metal-oxide nanoparticle-cell interactions
Peter Wick, Stephanie Grabmueller, Alke Petri-Fink, Barbara Rothen-Rutishauser (2014), Advanced human in vitro models to assess metal-oxide nanoparticle-cell interactions, in MRS Bulletin , 39(11), 984-989.
Fluorescence-encoded gold nanoparticles: library design and modulation of cellular uptake into dendritic cells
Rodriguez-Lorenzo L., Fytianos K., Blank F., von Garnier C., Rothen-Rutishauser B., Petri-Fink A. (2014), Fluorescence-encoded gold nanoparticles: library design and modulation of cellular uptake into dendritic cells, in Small, 10, 1341-1350.
Quantification of nanoparticles at the single-cell level: an overview about state-of-the-art techniques and their limitations
Vanhecke D., Rodriguez-Lorenzo L., Clift M.J., Blank F., Petri-Fink A., Rothen-Rutishauser B. (2014), Quantification of nanoparticles at the single-cell level: an overview about state-of-the-art techniques and their limitations, in Nanomedicine, 9, 1885-1900.
Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
Seydoux E., Rothen-Rutishauser B., Nita I.M., Balog S., Gazdhar A., Stumbles P.A., Petri-Fink A., Blank F., von Garnier C. (2014), Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation, in Int J Nanomedicine, 9, 3885-3902.
Bioavailability of silver nanoparticles and ions: from a chemical and biochemical perspective
Behra R., Sigg L., Clift M.J., Herzog F., Minghetti M., Johnston B., Petri-Fink A., Rothen-Rutishauser B. (2013), Bioavailability of silver nanoparticles and ions: from a chemical and biochemical perspective, in J R Soc Interface, 10, 20130396-20130396.
Assessing the in vitro and in vivo toxicity of superparamagnetic iron oxide nanoparticles.
Mahmoudi Morteza, Hofmann Heinrich, Rothen-Rutishauser Barbara, Petri-Fink Alke (2012), Assessing the in vitro and in vivo toxicity of superparamagnetic iron oxide nanoparticles., in Chemical reviews, 112(4), 2323-38.
Nanoparticles and cells: an interdisciplinary approach.
Petri-Fink Alke, Rothen-Rutishauser Barbara (2012), Nanoparticles and cells: an interdisciplinary approach., in Chimia, 66(3), 104-9.
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.
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, Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model., in ACS Nano, in press.
Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro
Fytianos K., Rodriguez-Lorenzo L., Clift M.J., Blank F., Vanhecke D., von Garnier C., Petri-Fink A., Rothen-Rutishauser B., Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro, in Nanomedicine: NBM.

Collaboration

Group / person Country
Types of collaboration
Phil Stumbles, Telethon Kids Institute, Perth. Australia Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Alke Fink, Co-Chair BioNanomaterials Group, Adolphe Merkle Institute Switzerland (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
20th Congress of International Society for Aerosols in Medicine Talk given at a conference Surface modified gold nanoparticles to specifically target lung immune cells in vitro 30.05.2015 Munich, Germany Fytianos Kleanthis;
20th Congress of International Society for Aerosols in Medicine Talk given at a conference Nanoparticles and the lung 30.05.2015 Munich, Germany Rothen-Rutishauser Barbara;
SENN2015 conference Talk given at a conference Opportunities and risks of nanomaterials – What can we learn by looking through a magnifying glass? 12.04.2015 Helsinki, Finland Rothen-Rutishauser Barbara;
NanoBio&Med Conference Talk given at a conference Biomedical nanopacarriers: the importance of size and surface charge in modulating the pulmonary immune system 11.03.2015 Bilbao, Spain Blank Fabian;
GSIA/SGVC Educational Course Nanotechnology Individual talk Creation and Application of Novel Nanocarriers for Vaccination and Drug Delivery Application 20.11.2014 Novartis Campus, Basel , Switzerland Rothen-Rutishauser Barbara;
Annual Meeting of the Swiss Respiratory Society Poster Nanoparticles decrease antigen-processing in dendritic cells without affecting other cell functions 08.05.2014 Interlaken, Switzerland Seydoux Emilie;
7th Nanotoxicology conference Talk given at a conference Nanoparticles and lung epithelial barriers – what we know and where to go from here 25.04.2014 Antalya, Turkey Rothen-Rutishauser Barbara;
Nanotox 2014 Poster Surface modification of gold nanoparticles can modulate uptake by dendritic cells, while functional and immunological properties remain unaltered 23.04.2014 Antalya, Turkey Fytianos Kleanthis;
Annual Meeting of International Society of Aerosol Medicine Talk given at a conference DELIVERY OF ANTIGENS FOR VACCINATION: RECENT ADVANCES AND CHALLENGES. 06.04.2014 Chapel Hill, North Carolina, United States of America Blank Fabian;
World Immune Regulation Meeting (WIRM) VIII Poster Particulate size modulates antigen processing in dendritic cells 19.03.2014 Davos, Switzerland Seydoux Emilie;
Wissenschaftliche Grundlagen zur Regulation von Nanomaterialien Individual talk Interaktion von Nanopartikeln mit biologischen Systemen 20.01.2014 Oekotoxzentrum – Dübendorf , Switzerland Rothen-Rutishauser Barbara;
European Respiratory Society Annual Congress Poster Functional modulation of bone marrow-derived dendritic cells depends on polystyrene particles size 07.09.2013 Barcelona, Spain Seydoux Emilie;
Microscopy Conference (MC) Talk given at a conference Delivery of nanocarriers for pulmonary vaccination: recent advances and challenges 25.08.2013 Regensburg, Germany Blank Fabian;
11th International Conferences on Nanosciences and Nanotechnologies Talk given at a conference Surface functionalization of gold nanoparticles influences cellular uptake but it has not effect in the functional properties of human dendritic cells 09.07.2013 Thessaloniki, Greece Fytianos Kleanthis;
Joint Annual Meeting of the Swiss Society of Allergology and Immunology and the Swiss Respiratory Society Talk given at a conference Functionalized gold nanoparticles to modulate the immune response in human lung dendritic cells 17.04.2013 Davos, Switzerland Fytianos Kleanthis;
European Respiratory Society, Lung Science Conference Poster Functional modulation of bone marrow-derived dendritic cells depends on polystyrene particles size 15.03.2013 Estoril, Portugal Seydoux Emilie;
World Immune Regulation Meeting (WIRM) VII Poster Dendritic cells as a target for specifically designed gold nanoparticles – can we modulate the immune response 13.03.2013 Davos, Switzerland Fytianos Kleanthis;
9th International Conference on Nanoscience & Nanotechnologies Talk given at a conference Effects of PEGylated gold nanoparticles on surface marker expression and antigen uptake in dendritic cells 03.07.2012 Thessaloniki, Greece Fytianos Kleanthis;
10th International Conferences on Nanosciences and Nanotechnologies Talk given at a conference Effects of PEGylated gold nanoparticles on surface marker expression and antigen uptake in dendritic cells 30.06.2012 Thessaloniki, Greece Fytianos Kleanthis;
Annual Meeting of the American Thoracic Society Talk given at a conference Size determines particle uptake efficiency and trafficking by prominent respiratory tract antigen presenting cell populations 18.05.2012 San Francisco, United States of America von Garnier Christophe;
CLINAM Talk given at a conference Nanoparticles and the Pulmonary Immune System” 06.05.2012 Basel, Switzerland Rothen-Rutishauser Barbara;
Annual Meeting of the European Respiratory Society Poster Different antigen presenting cell populations in the respiratory tract show size dependent particle uptake efficiency during steady state and allergic airways inflammation 24.09.2011 Amsterdam, Netherlands Blank Fabian;


Self-organised

Title Date Place
10th Swiss Aerosol Group Meeting 02.11.2015 Bern, Switzerland
9th Swiss Aerosol Group Meeting 10.11.2014 Bern, Switzerland
8th Swiss Aerosol Group Meeting 18.11.2013 Bern, Switzerland
7th Swiss Aerosol Group Meeting 20.11.2012 Bern, Switzerland
6th Swiss Aerosol Group Meeting 02.11.2011 Bern, Switzerland

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Nanopodium Solothurn Workshop 20.04.2015 Solothurn, Switzerland Rothen-Rutishauser Barbara;
Expo Nano – Umwelt Arena Spreitenbach Talk 22.02.2014 Spreitenbach, Switzerland Rothen-Rutishauser Barbara;


Self-organised

Title Date Place
AMI Tag der offen Tür 29.11.2014 Fribourg, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Nanos – die unbekannten Zwerge – auch in Pflanzenschutzmitteln Bauernzeitung Online German-speaking Switzerland 2014
New media (web, blogs, podcasts, news feeds etc.) Was Sie schon immer über Nano wissen wollten – oder warum Interdisziplinarität am Adolphe Merkle Ins Bundesamt für Gesundhet German-speaking Switzerland 2013
Print (books, brochures, leaflets) A particular therapy International 2012
Video/Film Immunotherapy Western Switzerland 2012
New media (web, blogs, podcasts, news feeds etc.) Weniger Nebenwirkungen Interpharma News German-speaking Switzerland 2012

Awards

Title Year
Best oral presentation, ISAM Conference in Munich 2015
Prix Fond Carlo de La Fondation Philanthropia 2015 2015
Egon Naef Prize 2014 for research on in vitro alternative methods 2014
Young Investigator bursary for travel and accommodation, ERS Lung Science conference, Estoril, Portugal 2013
Forschungsbeitrag der Schweizerischen Gesellschaft für Pneumologie 2012
GlaxoSmithKline-Pneumo-Preis 2011 der Schweizerischen Gesellschaft für Pneumologie 2011

Associated projects

Number Title Start Funding scheme
159847 Towards a fundamental understanding of nanoparticle exocytosis from cells 01.10.2015 Project funding
145003 A new Zeiss LSM 710 laser scanning microscope for the DCR LCI Core Facility 01.12.2012 R'EQUIP
139226 IncuCyte-based high throughput imaging-based platform for determination of cellular and molecular events in real time in cultured cells in vitro: application to nanomaterial studies, cancer and cardiovascular research 01.12.2011 R'EQUIP
157748 Microscopy Equipment for Organ-on-Chips and Perfused Microfluidic Systems with High Speed Camera 01.12.2014 R'EQUIP
146249 Pulmonary immune responses to bio-mimetic antigen carriers for novel therapeutic approaches to treating allergic asthma 01.08.2013 Project funding
138365 Realistic exposure scenarios to study nanoparticle-lung cell interactions 01.01.2012 Project funding

Abstract

The aetiology of allergic asthma is multi-factorial and triggered by a skewed immune response to innocuous airborne allergens such as dust mite allergen and pollen. Despite intense research, rates of allergy and allergy-induced asthma continue to rise in most industrialised nations and also in emerging countries. Nanoparticles (NP) synthesised by nanotechnology may have many different shapes and chemical compositions, therefore their properties can be specifically designed for clinical diagnostic and therapeutic applications. Recent studies have shown that NP can stimulate or suppress various immune response pathways; however the effects of NP on the immune system in relation to the particle properties (size, surface modification, solubility and shape) are unknown to date.In order to harness the unique properties of NP for novel clinical applications in the treatment of allergic respiratory disease, we propose to develop and utilise specifically designed NP to investigate immune-modulatory and anti-inflammatory effects in the lung with various experimental approaches: (I) In vitro systems of the human lung to evaluate the trafficking of NP by macrophages (innate immune system) and dendritic cells (adaptive immune system), as well as their potentially associated immune-modulatory effects and nano-immunotoxicity.(II) In vivo assays, i.e. allergic respiratory disease models, to evaluate the immune-modulatory potential of NP and adverse nano-immunotoxic effects.The aim of the proposed project is to specifically evaluate designed NP as pulmonary anti-allergic nanovaccines for the treatment of allergic asthma by utilising established methods to investigate immune-modulatory effects and study possible associated health risks such as nano-immunotoxicity.
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