Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in early human placental explants and reduce hCG secretion

Abstract

A thorough understanding of nanoparticle bio-distribution at the feto-maternal interface will be a prerequisite for their diagnostic or therapeutic application in women of childbearing age and for teratologic risk assessment. Therefore, the tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG-NPs) with first- trimester human placental explants were analyzed and compared to less sophisticated trophoblast-cell based models. First-trimester human placental explants, BeWo cells and primary trophoblast cells from human term placenta were exposed to fluorescence labeled, ∼5 nm dPG-NPs, with differently charged surfaces, at concentrations of 1 µM and 10 nM, for 6 and 24 h. Accumulation of dPGs was visualized by fluorescence microscopy. To assess the impact of dPG-NP on trophoblast integrity and endocrine function, LDH, and hCG releases were measured. A dose- and charge-dependent accumulation of dPG-NPs was observed at the early placental barrier and in cell lines, with positive dPG-NP-surface causing deposits even in the mesenchymal core of the placental villi. No signs of plasma membrane damage could be detected. After 24 h we observed a significant reduction of hCG secretion in placental explants, without significant changes in trophoblast apoptosis, at low concentrations of charged dPG-NPs. In conclusion, dPG-NP’s surface charge substantially influences their bio-distribution at the feto-maternal interface, with positive charge facilitating trans-trophoblast passage, and in contrast to more artificial models, the first-trimester placental explant culture model reveals potentially hazardous influences of charged dPG-NPs on early placental physiology.

Keywords:

• Dendritic polyglycerol nanoparticles
• early human placenta
• hCG
• BeWo
• primary trophoblasts
• nanotoxicology

Acknowledgments

We want to thank Andreas Glasner for providing first-trimester placenta specimen, the Department of Obstetrics and Gynecology, Medical University of Graz, for providing term placenta samples and Dominik Gröger for providing synthetic precursors polymers. We also thank Rebekka Prokschi, Sabine Maninger, Rudolf Schmied and Andrea Wöls for excellent technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Martin Gauster was supported by funds of the Oesterreichische Nationalbank, Anniversary Fund, project number: 16513, and by the Austrian Science Fund (FWF): P29639 and I3304. Herbert Juch was supported by the Franz Lanyar Stiftung grant #350. Sabine Reimann is grateful to the IMPRS on Multiscale Biosystems for financial support.