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.

中文翻译：

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树突状聚甘油纳米颗粒在早期人胎盘外植体中显示电荷依赖性生物分布，并减少hCG分泌

深入了解胎儿-母亲界面上的纳米颗粒生物分布，将是其在育龄妇女中进行诊断或治疗应用以及进行致畸风险评估的先决条件。因此，分析了生物相容性树突状聚甘油纳米颗粒（dPG-NPs）与早孕期人胎盘外植体的组织相互作用，并将其与不太复杂的基于滋养层细胞的模型进行了比较。早孕期人胎盘外植体，BeWo细胞和人足底胎盘的原代滋养细胞暴露于荧光标记的〜5 nm dPG-NPs，其表面电荷不同，浓度分别为1 µM和10 nM，分别为6和24 h。dPG的积累通过荧光显微镜观察。为了评估dPG-NP对滋养层完整性和内分泌功能LDH的影响，测量了hCG的释放。在早期胎盘屏障和细胞系中观察到剂量依赖性和电荷依赖性的dPG-NP积累，dPG-NP表面阳性甚至在胎盘绒毛的间充质核中也引起沉积。没有发现质膜受损的迹象。24小时后，我们观察到在低浓度的带电dPG-NPs下，胎盘外植体中hCG分泌显着减少，而滋养层细胞凋亡却无明显变化。总之，dPG-NP的表面电荷在胎儿-母体界面上大大影响了它们的生物分布，带正电荷促进了滋养层细胞的通过，并且与更多的人工模型相比，孕早期的胎盘外植体培养模型显示出潜在的有害影响dPG-NPs对早期胎盘生理的影响。