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Nanoparticle tracking and oxidative stress biomarkers in healthy non-smoking volunteers

English title Nanoparticle tracking and oxidative stress biomarkers in healthy non-smoking volunteers
Applicant Riediker Michael
Number 131282
Funding scheme NRP 64 Opportunities and Risks of Nanomaterials
Research institution Institut universitaire romand de Santé au Travail UNISANTÉ
Institution of higher education Institute for Work and Health - IST
Main discipline Pharmacology, Pharmacy
Start/End 01.08.2011 - 30.11.2015
Approved amount 350'000.00
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All Disciplines (5)

Discipline
Pharmacology, Pharmacy
Cardiovascular Diseases
Respiratory Diseases
Occupational Medicine, Ergonomy
Cardiovascular Research

Keywords (13)

nanoparticles; translocation; inhalation; superparamagnetic iron oxide nanoparticles-SPIONs; tobacco smoke nanoparticles; exhaled breath condensate; blood; urine; fluorescence; oxidative stress; human subject research; exposure; airborne particulate matter

Lay Summary (English)

Lead
Lay summary
The lungs are an excellent entry portal for gases and aerosol-transported molecules as they present a high surface area with thin epithelial barrier in addition to extensive vasculature. Nanoparticles (NPs) are studied for pulmonary administration of pharmaceutical agents since they present a longer retention time and allow for the prolonged release of loaded drugs. The same properties, however, pose a health risk for the case of non-medical NPs. NPs can transfer to novel target organs, and catalytically active NPs can generate oxidative stress, which can damage cells and launch a cascade of effects, contributing to acute and chronic diseases.The lung lining fluid is the initial point of contact for inhaled NPs. The processes in this liquid and the relation to other bodily liquids are essential for the understanding of the full chain of toxicological and pharmacokinetic events. We propose to study two main hypotheses:A)Inhaled nanoparticles that deposit in the lung become suspended in lung lining fluid and subsequently translocate into the circulation. B)Only reactive particles initiate an increase in oxidative stress in the lung lining fluid, which is then followed by an increase in oxidative stress markers in circulation and urine.We will address these hypotheses with the following specific activities:1)We will expose healthy non-smoking human volunteers to fluorescently labelled PVA-SPIONs (by inhalation) and quantitatively characterize the deposition and translocation of the PVA-SPIONs. Exhaled breath condensate will be collected as a surrogate of lung lining fluid and blood and urine will be collected to assess translocation into systemic circulation.2)We will expose the volunteers to reactive (tobacco smoke) in addition to the nonreactive (PVA-SPIONs) particles to demonstrate that there is a significant and clear difference between the levels of biomarkers of oxidative stress in the biological fluids of the different exposure groups.3)We will collect samples at several timepoints before and after exposure to study the timing of translocation and oxidative stress response in the different compartments and the correlation between these markers and the exposure levels.At the conclusion, we will have demonstrated the feasibility to study NPs in lung lining fluid and their translocation by collecting labeled SPIONs in EBC, blood and urine. We will also better understand how the oxidative stress response at the initial deposition site is linked to the systemic response and how this is reflected in urine.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Physicochemical Characterization of Nebulized Superparamagnetic Iron Oxide Nanoparticles (SPIONs).
Graczyk H Bryan LC Lewinski N Suarez G Coullerez G Bowen P Riediker M. (2014), Physicochemical Characterization of Nebulized Superparamagnetic Iron Oxide Nanoparticles (SPIONs)., in J Aerosol Med Pulm Drug Deliv. , 27(0), 1-9.
Human inhalation exposure to iron oxide particles
Lewinski Nastassja Graczyk Halshka Riediker Michael (2013), Human inhalation exposure to iron oxide particles, in BioNanoMaterials , 14(1-2), 5-23.
Characterization of Tungsten Inert Gas (TIG) Welding Fume Generated by Apprentice Welders
Graczyk Halshka, Lewinski Nastassja, Zhao Jiyuan, Concha-Lozano Nicolas, Riediker Michael, Characterization of Tungsten Inert Gas (TIG) Welding Fume Generated by Apprentice Welders, in Annals of Occupational Hygiene , 15.

Collaboration

Group / person Country
Types of collaboration
Powder Technology Laboratory, École polytechnique fédérale de Lausanne (EPFL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Clinical Research Center, CHUV Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Electron Microscopy Facility, University of Lausanne (UNIL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
University Centre of Legal Medicine (CURML) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
EDEL-for-Life, PSE-B/EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Laboratory of Inorganic Chemistry, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
National Institute for Occupational Safety and Health (NIOSH) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
RIKILT- Institute of Food Safety, Wageningen UR Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
7th International Symposium on Nanotechnology : Occupational and Environmental Health Talk given at a conference Characterization of Tungsten Inert Gas (TIG) welding fume generated by apprentice welders and resulting oxidative stress biomarker analysis 18.10.2015 Limpopo, South Africa Sauvain Jean-Jacques; Riediker Michael; Graczyk Halshka;
7th International Symposium on Nanotechnology : Occupational and Environmental Health Talk given at a conference A method for preservation and determination of welding fume nanoparticles in exhaled breath condensate 18.10.2015 Limpopo, South Africa Riediker Michael; Graczyk Halshka;
Module for the Diploma of Advanced Studies in Work and Health Individual talk Occupational Safety and Health Control Strategies 11.05.2015 Lausanne, Institute of Work and Health , Switzerland Graczyk Halshka;
Memorial Conference to honor the late Dr. Wojtek Lubinski, Invited Speaker Talk given at a conference Translocation and Oxidative Stress of Inhaled Particles (Stres Oksydacyjny i Translokacja Wdychanych Nanocząsteczek, in Polish) 24.04.2015 Polish Institute of Medicine, Warsaw , Poland Graczyk Halshka;
NRP 64 4th and final Progress Report Meeting Talk given at a conference Nanoparticle tracking and oxidative stress biomarkers in non-smoking volunteers 26.03.2015 Fribourg , Switzerland Sauvain Jean-Jacques; Riediker Michael; Graczyk Halshka;
Swiss Aerosol Group Meeting Individual talk Characterization of Tungsten Inert Gas (TIG) Welding Fumes Generated by Welding Apprentices in Switzerland 10.11.2014 Bern , Switzerland Graczyk Halshka;
ProDoc Health@Work Meeting Individual talk Nanoparticle tracking and oxidative stress biomarkers 03.11.2014 Solothurn , Switzerland Graczyk Halshka;
9th Annunal Polish-French Pneumologie Meeting Talk given at a conference Détection de nanoparticules inhalées et de leurs effets biologiques 03.10.2014 Szczecin, Poland Graczyk Halshka;
3rd Workplace Indoor Aerosols Conference Talk given at a conference Inhaled nanoparticle tracking and oxidative stress biomarkers in apprentice welders 14.05.2014 Wroclaw, Poland, Poland Graczyk Halshka;
NANOTOX, 7th International Nanotoxicology Congress Poster Physicochemical Characterization of Nebulized Superparamagnetic Iron Oxide Nanoparticles (SPIONs). 24.04.2014 Antalya, Turkey, Turkey Graczyk Halshka; Riediker Michael;
NRP 64 3rd Progress Report Meeting Poster Nanoparticle tracking and oxidative stress biomarkers in non-smoking volunteers 06.03.2014 Zurich , Switzerland Riediker Michael; Sauvain Jean-Jacques; Bowen Paul; Graczyk Halshka;
ProDoc health@work colloqium Individual talk Nanoparticle tracking and oxidative stress biomarkers 05.03.2014 Bern , Switzerland Graczyk Halshka;
6th International Symposium on Nanotechnology, Occupational and Environmental Health (NanOEH) Talk given at a conference A novel human exposure system for nanoparticle tracking and oxidative stress assessment 28.10.2013 Nagoya, Japan, Japan Graczyk Halshka; Riediker Michael;
NRP 64 2nd Progress Report Meeting Individual talk Nanoparticle tracking and oxidative stress biomarkers in non-smoking volunteers 21.03.2013 Lausanne , Switzerland Riediker Michael; Bowen Paul; Graczyk Halshka; Sauvain Jean-Jacques;
Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin, Jahrestagung der Oesterreichischen Gesellschaft für Arbeitsmedizin Poster A human exposure system for nanoparticle tracking and oxidative stress biomarker assessment: developing a novel methodology for future occupational applications 13.03.2013 Bregenz, Austria Graczyk Halshka;
2nd QNano Integrating Conference Poster A human exposure system for nanoparticle tracking and oxidative stress biomarker assessment : developing a novel methodology for future occupational applications 27.02.2013 Prague , Czech Republic Graczyk Halshka; Riediker Michael;
NRP 64 1st Progress Report Meeting Talk given at a conference Nanoparticle tracking and oxidative stress biomarkers in healthy non-smoking volunteers 29.03.2012 Bern, Switzerland Sauvain Jean-Jacques; Bowen Paul; Riediker Michael;
NRP64 Kick-off meeting for researchers (3 to 4 March 2011) Talk given at a conference Nanoparticle tracking and oxidative stress biomarkers in healthy non-smoking volunteers 01.08.2011 Nottwil, Switzerland Sauvain Jean-Jacques; Clark Katherine; Riediker Michael; Bowen Paul;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Health effects of inhaled particles Western Switzerland 2015
Media relations: radio, television Comment la pollution de l’air accélère le vieillissement RTS - 36.9 Western Switzerland 2014
Talks/events/exhibitions Health effects of inhaled welding fume nanoparticles Western Switzerland 2014

Awards

Title Year
Health at Work Professional Doctorate Distinction 2015

Abstract

The lungs are an excellent entry portal for gases and aerosol-transported molecules as they present a high surface area with thin epithelial barrier in addition to extensive vasculature. Nanoparticles (NPs) are studied for pulmonary administration of pharmaceutical agents since they present a longer retention time and allow for the prolonged release of loaded drugs. The same properties, however, pose a health risk for the case of non-medical NPs. NPs can transfer to novel target organs, and catalytically active NPs can generate oxidative stress, which can damage cells and launch a cascade of effects, contributing to acute and chronic diseases.The lung lining fluid is the initial point of contact for inhaled NPs. The processes in this liquid and the relation to other bodily liquids are essential for the understanding of the full chain of toxicological and pharmacokinetic events. We propose to study two main hypotheses:A)Inhaled nanoparticles that deposit in the lung become suspended in lung lining fluid and subsequently translocate into the circulation. B)Only reactive particles initiate an increase in oxidative stress in the lung lining fluid, which is then followed by an increase in oxidative stress markers in circulation and urine.We will address these hypotheses with the following specific activities:1)We will expose healthy non-smoking human volunteers to fluorescently labelled PVA-SPIONs (by inhalation) and quantitatively characterize the deposition and translocation of the PVA-SPIONs. Exhaled breath condensate will be collected as a surrogate of lung lining fluid and blood and urine will be collected to assess translocation into systemic circulation.2)We will expose the volunteers to reactive (tobacco smoke) in addition to the nonreactive (PVA-SPIONs) particles to demonstrate that there is a significant and clear difference between the levels of biomarkers of oxidative stress in the biological fluids of the different exposure groups.3)We will collect samples at several timepoints before and after exposure to study the timing of translocation and oxidative stress response in the different compartments and the correlation between these markers and the exposure levels.At the conclusion, we will have demonstrated the feasibility to study NPs in lung lining fluid and their translocation by collecting labeled SPIONs in EBC, blood and urine. We will also better understand how the oxidative stress response at the initial deposition site is linked to the systemic response and how this is reflected in urine.
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