Abstract
Graphene oxide (GO) is considered a promising 2D material for biomedical applications. However, the biological health effects of GO are not yet fully understood, in particular for highly sensitive populations such as pregnant women and their unborn children. Especially the potential impact of GO on the human placenta, a transient and multifunctional organ that enables successful pregnancy, has not been investigated yet. Here we performed a mechanistic in vitro study on the placental uptake and biological effects of four non-labelled GO with varying physicochemical properties using the human trophoblast cell line BeWo. No overt cytotoxicity was observed for all GO materials after 48 h of exposure at concentrations up to 40 µg ml−1. However, exposure to GO materials induced a slight decrease in mitochondrial activity and human choriogonadotropin secretion. In addition, GO induced a transient opening of the trophoblast barrier as evidenced by a temporary increase in the translocation of sodium fluorescein, a marker molecule for passive transport. Evidence for cellular uptake of GO was found by transmission electron microscopy analysis, revealing uptake of even large micro-sized GO by BeWo cells. Although GO did not elicit major acute adverse effects on BeWo trophoblast cells, the pronounced cellular internalization as well as the potential adverse effects on hormone release and barrier integrity warrants further studies on the long-term consequences of GO on placental functionality in order to understand potential embryo-fetotoxic risks.
Highlights
Nanomaterials have attracted great attention as candidates for nanomedical applications, e.g. as contrast agents and drug nanocarriers [1]
Structural properties were studied by transmission electron microscopy (TEM), and atomic force microscopy (AFM) showing that the average lateral dimensions of l-graphene oxide (GO) and s-GO are between 5–30 μm and 0.05–1 μm, respectively (figures 1(a) and (b) and table 1)
BeWo cells are widely used as a surrogate for villous cytotrophoblasts or the invasive extravillous trophoblast population.These cells exhibit several characteristics of human trophoblasts in vivo including the production of placental hormones or the capacity to fuse and undergo morphological and biochemical differentiation in the presence of forskolin
Summary
Nanomaterials have attracted great attention as candidates for nanomedical applications, e.g. as contrast agents and drug nanocarriers [1]. Targeted drug delivery using nanoparticles (NPs) offers the possibility to deliver drugs to specific cells and tissues which increases efficacy and enables to minimize undesired side effects of the drug. Concerns have been raised regarding potential adverse effects of NPs entering the blood stream, especially for sensitive populations including pregnant women and developing fetus. Graphene-related materials (GRM) and other 2D materials have recently attracted a lot of interest in respect to nano- and biomedical application [9,10,11,12,13,14,15,16,17,18]. Water dispersible graphene oxide (GO) is under investigation as potential drug delivery platform [19]. A recent study in mice has demonstrated rapid clearance of GO from the blood stream after intravenous application [10]. GO has the potential to reach the placenta in significant amounts as this is a highly perfused organ that is extensively exposed to circulating substances
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