Magnetic Nanoparticles Interact and Pass an In Vitro Co-Culture Blood-Placenta Barrier Model.

Elena Müller,Andreas Weidner,Christine Gräfe,Silvio Dutz,Joachim Clement,Christian Bergemann,Frank Wiekhorst

doi:10.3390/nano8020108

Abstract

Magnetic nanoparticles are interesting tools for biomedicine. Before application, critical prerequisites have to be fulfilled. An important issue is the contact and interaction with biological barriers such as the blood-placenta barrier. In order to study these processes in detail, suitable in vitro models are needed. For that purpose a blood-placenta barrier model based on the trophoblast-like cell line BeWo and primary placenta-derived pericytes was established. This model was characterized by molecular permeability, transepithelial electrical resistance and cell-cell-contact markers. Superparamagnetic iron oxide nanoparticles (SPIONs) with cationic, anionic or neutral surface charge were applied. The localization of the nanoparticles within the cells was illustrated by histochemistry. The time-dependent passage of the nanoparticles through the BeWo/pericyte barrier was measured by magnetic particle spectroscopy and atomic absorption spectroscopy. Cationically coated SPIONs exhibited the most extensive interaction with the BeWo cells and remained primarily in the BeWo/pericyte cell layer. In contrast, SPIONs with neutral and anionic surface charge were able to pass the cell layer to a higher extent and could be detected beyond the barrier after 24 h. This study showed that the mode of SPION interaction with and passage through the in vitro blood-placenta barrier model depends on the surface charge and the duration of treatment.

Highlights

Research activities concerning the utilization of nanomaterials in various fields, especially in nanomedicine, have rapidly grown in recent years
In order to study the effect of Superparamagnetic iron oxide nanoparticles (SPIONs) on the blood-placenta barrier, an in vitro co-culture model on the basis of the human cell line BeWo and human primary placental pericytes was established
It has to be noted that the detachment of the complete cell layer from the membrane is a technical artefact resulting from the multi-step sample preparation for this analysis method

Summary

Introduction

Research activities concerning the utilization of nanomaterials in various fields, especially in nanomedicine, have rapidly grown in recent years. Due to the plethora of promising applications of engineered nanoparticles in medicine, the amount of novel nanoparticular formulas is rising, too [1]. With respect to the therapeutic application of nanoparticles into the human body, pregnant women in particular embody a specific sensitive group of target persons. Special criteria have to be met when assessing the impact of such materials, especially regarding biodistribution, excretion and biocompatibility. For studying these effects on pregnant women, focus must be especially laid upon the blood-placenta-barrier (BPB), since the placenta is indispensable during pregnancy. To appropriately study the effects and potentially associated risks of novel nanomaterials in the placenta and especially the BPB, suitable in vitro models allowing high throughput are most helpful [5]

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Results

Conclusion