Division of Toxicology, Wageningen University, P.O. box 8000, 6700, EA, Wageningen, the Netherlands.
Wageningen Food Safety Research (WFSR), P.O. Box 230, 6700, AE, Wageningen, the Netherlands.
Part Fibre Toxicol. 2020 Mar 10;17(1):11. doi: 10.1186/s12989-020-00342-6.
Silver nanoparticles (AgNPs) are used extensively in various consumer products because of their antimicrobial potential. This requires insight in their potential hazards and risks including adverse effects during pregnancy on the developing fetus. Using a combination of the BeWo b30 placental transport model and the mouse embryonic stem cell test (EST), we investigated the capability of pristine AgNPs with different surface chemistries and aged AgNPs (silver sulfide (AgS) NPs) to cross the placental barrier and induce developmental toxicity. The uptake/association and transport of AgNPs through the BeWo b30 was characterized using ICP-MS and single particle (sp)ICP-MS at different time points. The developmental toxicity of the AgNPs was investigated by characterizing their potential to inhibit the differentiation of mouse embryonic stem cells (mESCs) into beating cardiomyocytes.
The AgNPs are able to cross the BeWo b30 cell layer to a level that was limited and dependent on their surface chemistry. In the EST, no in vitro developmental toxicity was observed as the effects on differentiation of the mESCs were only detected at cytotoxic concentrations. The aged AgNPs were significantly less cytotoxic, less bioavailable and did not induce developmental toxicity.
Pristine AgNPs are capable to cross the placental barrier to an extent that is influenced by their surface chemistry and that this transport is likely low but not negligible. Next to that, the tested AgNPs have low intrinsic potencies for developmental toxicity. The combination of the BeWo b30 model with the EST is of added value in developmental toxicity screening and prioritization of AgNPs.
由于银纳米粒子（AgNPs）具有抗菌潜力，因此被广泛应用于各种消费品中。这需要深入了解其潜在危害和风险，包括对发育中胎儿的妊娠期间的不良影响。本研究采用 BeWo b30 胎盘转运模型和小鼠胚胎干细胞试验（EST）相结合的方法，研究了不同表面化学性质的原始 AgNPs 和老化的 AgNPs（硫化银（AgS）NPs）穿过胎盘屏障并诱导发育毒性的能力。使用 ICP-MS 和单颗粒（sp）ICP-MS 在不同时间点来表征 AgNPs 在 BeWo b30 中的摄取/结合和转运。通过表征 AgNPs 抑制小鼠胚胎干细胞（mESCs）分化为搏动性心肌细胞的能力来研究 AgNPs 的发育毒性。
AgNPs 能够穿过 BeWo b30 细胞层，但程度有限，且取决于其表面化学性质。在 EST 中，未观察到体外发育毒性，因为只有在细胞毒性浓度下才会观察到对 mESCs 分化的影响。老化的 AgNPs 的细胞毒性显著降低，生物利用度降低，且不会引起发育毒性。
原始 AgNPs 能够穿过胎盘屏障，但程度受到其表面化学性质的影响，这种转运可能很低但并非可以忽略不计。此外，测试的 AgNPs 对发育毒性的内在潜力较低。BeWo b30 模型与 EST 的结合在发育毒性筛选和 AgNPs 的优先级确定方面具有附加价值。
