Project

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Nanoparticle Transport Across the Human Placenta

English title Nanoparticle Transport Across the Human Placenta
Applicant Wick Peter
Number 131232
Funding scheme NRP 64 Opportunities and Risks of Nanomaterials
Research institution Informatics & Sustainability Research Group Technologie und Gesellschaft Empa
Institution of higher education Swiss Federal Laboratories for Materials Science and Technology - EMPA
Main discipline Cellular Biology, Cytology
Start/End 01.05.2011 - 30.04.2014
Approved amount 346'253.00
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Keywords (4)

ex-vivo perfusion; barrier tissue; human placenta; nanoparticle

Lay Summary (English)

Lead
Lay summary
Humans have been exposed to fine and ultra fine particles throughout their history. Since the Industrial Revolution, sources, doses and types of nanoparticles have changed dramatically. In the last decade, the rapidly developing field of nanotechnology has led to an increase of engineered nanoparticles with novel physical and chemical properties. Regardless of whether this exposure is unintended or not, a careful assessment of possible adverse effects is needed. A large number of projects have been carried out to assess the consequences of combustion-derived or engineered nanoparticle exposure on human health. In recent years there has been a growing concern about the possible health influence of exposure to air pollutants during pregnancy, hence an implicit concern about potential risk for nanoparticle exposure in-utero. We could recently show that polystyrene (PS) particles up to a size of 200 - 300 nm were able to cross the placental barrier without affecting the viability of the explant. However after our first studies, it is still unclear how the NPs find their way through the placental barrier.Therefore the goal of this project is to identify the mechanisms which allow NPs to cross the placenta and study the impact of NPs on the placental tissue.The ex-vivo dual re-circulation human placental perfusion model will be used to investigate how nanoparticles can cross this barrier. Therefore we will apply fluorescently labeled PS beads (positively and negatively charged) as well as further NPs of different chemistry such as QDots, TiO2, SPIONs within a size range of 10 - 500 nm and fluorescently labeled CNTs to perfuse the explant.The accumulation and localization of the NPs, the viability of the explant including the detection of oxidative stress markers and the release of pro-inflammatory factors and a careful pathological assessment will be performed after perfusion. A special emphasis will be placed on the expression and activity of the multi drug resistance gene 1, an unspecific p-glycoprotein transporter and its role of NP transport across the placenta.The human placenta perfusion model is a powerful system to achieve a detailed understanding of the NP transport mechanism across the placental barrier. Today’s therapy of pregnant women has to avoid the dilemma that both organisms (mother and child) can be affected by a treatment although only one of them should be treated. This project will not only deliver a nano-toxicological study but also provide the basis for the development of target orientated treatments.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Metal oxide nanoparticle - cell interactions: how advanced human in vitro models improve the understanding of the biological effects
Wick P Grafmüller S Fink-Petri A Rothen-Rutishauser B (2014), Metal oxide nanoparticle - cell interactions: how advanced human in vitro models improve the understanding of the biological effects, in MRS Bulletin, 39, 984-989.
Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model.
Grafmüller Stefanie, Manser Pius, Krug Harald F, Wick Peter, von Mandach Ursula (2013), Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model., in Journal of visualized experiments : JoVE, (76), 1.
Knocking at the door of the unborn child: engineered nanoparticles at the human plcental barrier
Bürki-Thurnherr Tina, von Mandach Ursula, Wick Peter (2012), Knocking at the door of the unborn child: engineered nanoparticles at the human plcental barrier, in Swiss Medical Weekly, 142, w13559--.

Collaboration

Group / person Country
Types of collaboration
Universität Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Dr. Heinrich Hofmann, Laboratory of Powder Technology (LTP), EPF Lausanne Switzerland (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
GCB (Graduate School for Celluar and Biomedical Sciences) PhD Symposium 2014 Talk given at a conference Transfer of engineered nanoparticles across the human placenta 29.01.2014 Bern, Switzerland Grafmüller Stefanie;
Swiss Aerosol Group Meeting 2013 Talk given at a conference Transfer of engineered nanoparticles across the human placenta 18.11.2013 Bern, Switzerland Wick Peter; Grafmüller Stefanie;
6th Annual Meeting of the Swiss Association of Perinatal Pharmacology (SAPP) Poster Nanoparticle transport across the human placenta 14.11.2013 Zürich, Switzerland von Mandach Ursula; Grafmüller Stefanie;
Seminar Series at the Department of Obstetrics, USZ Individual talk Placental transfer of nanoparticles 31.10.2013 Zürich, Switzerland Grafmüller Stefanie; von Mandach Ursula;
Empa PhD Symposium 2013 Talk given at a conference Transfer of engineered nanoparticles across the human placenta 23.10.2013 Dübendorf, Switzerland Grafmüller Stefanie;
49th Congress of the European Societies of Toxicology Talk given at a conference Transfer of engineered nanoparticles across the human placenta 01.09.2013 Interlaken, Switzerland Grafmüller Stefanie;
Annual Meeting of the European Foundation for Clinical Nanomedicine (CLINAM) 2013 Talk given at a conference Nanoaprticle transport across the human placenta 25.06.2013 Basel, Switzerland Wick Peter;
Annual Meeting of the Life Sciences Switzerland LS2 2013 Poster Nanoparticle transport across the human placenta 31.01.2013 Zürich, Switzerland Wick Peter; Grafmüller Stefanie;
5th Annual Meeting of the Swiss Association of Perinatal Pharmacology (SAPP) Poster Nanoparticle transport across the human placenta 29.11.2012 Zürich, Switzerland von Mandach Ursula; Grafmüller Stefanie;
Empa PhD Symposium 2012 Poster Nanoparticle transport across the human placenta 13.11.2012 Dübendorf, Switzerland Grafmüller Stefanie;
Bioengineering Seminar Series at the Department of Cranio-Maxillofacial Surgery, USZ Individual talk Nanoparticle transport across the human placenta 18.10.2012 Zürich, Switzerland von Mandach Ursula; Grafmüller Stefanie;
Jahreskongress der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe (SGGG) 2012 Poster Nanoparticle transport across the human placenta 28.06.2012 Interlaken, Switzerland Grafmüller Stefanie; von Mandach Ursula;
5th European Human Placental Perfusion Workshop Talk given at a conference Determination of the physicochemical properties responsible for the transplacental translocation of nanomaterials by using the human ex vivo placental perfusion model 14.06.2012 Manchester, Great Britain and Northern Ireland Wick Peter; Grafmüller Stefanie;
9th International Conference and Workshop on Biological Barriers Talk given at a conference Modeling the placenta barrier 05.03.2012 Saarbrücken, Deutschland, Germany Wick Peter;
Swiss carbon nanotubes information exchange workshop Talk given at a conference 'The Janus face of carbon nanotubes: A health and safety perspective' (Peter Wick) and 'Nanoparticle transport across the human placenta' (Stefanie Grafmüller) 23.01.2012 EAWAG, Dübendorf, Switzerland, Switzerland Grafmüller Stefanie; Wick Peter;
7th Empa PhD Symposium Poster Nanoparticle transport across the human placenta 18.10.2011 Empa St. Gallen, Switzerland, Switzerland Grafmüller Stefanie;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Weiterbildung Hebammen Kantonsspital St. Gallen und Klinik Hirslanden 22.08.2013 St. Gallen, Switzerland Wick Peter;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Mutter, Kind und Nanopartikel St. Galler Tagblatt German-speaking Switzerland 2011

Awards

Title Year
Best Poster Prize, 5th Annual Meeting of the Swiss Association of Perinatal Pharmacology, Zurich, CH 2012
Poster Prize, Empa PhD Symposium, Dübendorf, CH 2012

Abstract

Humans have been exposed to fine and ultra fine particles throughout their history. Since the Industrial Revolution, sources, doses and types of nanoparticles have changed dramatically. In the last decade, the rapidly developing field of nanotechnology has led to an increase of engineered nanoparticles with novel physical and chemical properties. Regardless of whether this exposure is unintended or not, a careful assessment of possible adverse effects is needed. A large number of projects have been carried out to assess the consequences of combustion-derived or engineered nanoparticle exposure on human health. In recent years there has been a growing concern about the possible health influence of exposure to air pollutants during pregnancy, hence an implicit concern about potential risk for nanoparticle exposure in-utero. We could recently show that polystyrene (PS) particles up to a size of 200 - 300 nm were able to cross the placental barrier without affecting the viability of the explant. However after our first studies, it is still unclear how the NPs find their way through the placental barrier.Therefore the goal of this project is to identify the mechanisms which allow NPs to cross the placenta and study the impact of NPs on the placental tissue.The ex-vivo dual re-circulation human placental perfusion model will be used to investigate how nanoparticles can cross this barrier. Therefore we will apply fluorescently labeled PS beads (positively and negatively charged) as well as further NPs of different chemistry such as QDots, TiO2, SPIONs within a size range of 10 - 500 nm and fluorescently labeled CNTs to perfuse the explant.The accumulation and localization of the NPs, the viability of the explant including the detection of oxidative stress markers and the release of pro-inflammatory factors and a careful pathological assessment will be performed after perfusion. A special emphasis will be placed on the expression and activity of the multi drug resistance gene 1, an unspecific p-glycoprotein transporter and its role of NP transport across the placenta.The human placenta perfusion model is a powerful system to achieve a detailed understanding of the NP transport mechanism across the placental barrier. Today’s therapy of pregnant women has to avoid the dilemma that both organisms (mother and child) can be affected by a treatment although only one of them should be treated. This project will not only deliver a nano-toxicological study but also provide the basis for the development of target orientated treatments.
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