Project

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

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.

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Last update: 21.02.2013

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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.