Gold nanoparticle distribution in advanced in vitro and ex vivo human placental barrier models

Abstract

BackgroundGold nanoparticles (AuNPs) are promising candidates to design the next generation NP-based drug formulations specifically treating maternal, fetal or placental complications with reduced side effects. Profound knowledge on AuNP distribution and effects at the human placental barrier in dependence on the particle properties and surface modifications, however, is currently lacking. Moreover, the predictive value of human placental transfer models for NP translocation studies is not yet clearly understood, in particular with regards to differences between static and dynamic exposures. To understand if small (3–4 nm) AuNPs with different surface modifications (PEGylated versus carboxylated) are taken up and cross the human placental barrier, we performed translocation studies in a static human in vitro co-culture placenta model and the dynamic human ex vivo placental perfusion model. The samples were analysed using ICP-MS, laser ablation-ICP-MS and TEM analysis for sensitive, label-free detection of AuNPs.ResultsAfter 24 h of exposure, both AuNP types crossed the human placental barrier in vitro, although in low amounts. Even though cellular uptake was higher for carboxylated AuNPs, translocation was slightly increased for PEGylated AuNPs. After 6 h of perfusion, only PEGylated AuNPs were observed in the fetal circulation and tissue accumulation was similar for both AuNP types. While PEGylated AuNPs were highly stable in the biological media and provided consistent results among the two placenta models, carboxylated AuNPs agglomerated and adhered to the perfusion device, resulting in different cellular doses under static and dynamic exposure conditions.ConclusionsGold nanoparticles cross the human placental barrier in limited amounts and accumulate in placental tissue, depending on their size- and/or surface modification. However, it is challenging to identify the contribution of individual characteristics since they often affect colloidal particle stability, resulting in different biological interaction in particular under static versus dynamic conditions. This study highlights that human ex vivo and in vitro placenta models can provide valuable mechanistic insights on NP uptake and translocation if accounting for NP stability and non-specific interactions with the test system.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0406-6) contains supplementary material, which is available to authorized users.

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

“…The transport of PSNPs was described to be size dependent, where transport of 50 nm PSNPs was six times higher than that of 100 nm PSNPs [16]. The placental transport of AuNPs also showed a size-dependency, where 10 to 30 nm AuNPs did not cross the placental barrier [47] and the smaller 3 and 4 nm AuNP crossed the placental barrier [21]. Upon the exposure of either the BeWo b30 (up to 24 h) or the perfused human placenta (up to 6 h) to 25 and 50 nm silica NPs, no placental transport could be detected [24].…”

“…The placental barrier has received special consideration in the field of toxicology as fetal exposure to NPs might be associated with reduced fetal growth and embryotoxicity [16][17][18][19]. NPs uptake and transport across the placental barrier has been reported to be dependent on the surface chemistry, size, and the chemical composition of the NPs [20,21]. To date, several alternative in vitro and ex vivo models have been developed and used to study the transport of NPs across the human placental barrier, i.e.…”

Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies

“…, BeWo b30) and endothelial cells (i.e. , primary human placental pericytes (hPC-PL) or human SV40-transformed microvascular placental venous endothelial cells (HPEC-A2) ( N = 5) [ 31 , 33 – 36 ], and (iii) a 3D co-culture of trophoblastic cells (i.e. , BeWo b30) and fibroblastic cells (i.e.…”

Antibodies for Venezuelan Equine Encephalitis Virus Protect Embryoid Bodies from Chikungunya Virus

“…Although scientists aim for model complexity in order to better replicate the placenta, the trans-well assay excels because it lends well to standardization and is easy to manipulate and reproduce [23,26]. For this study, we employed the trans-well approach due to its success in measuring the movement of nanoparticles across the placenta [27][28][29][30]. We followed Aengenheister et al (2018) [27] by including an embryoid body (EB) in our co-culture model.…”

“…We followed other research and used maternal syncytiotrophoblast and fetal umbilical vein cells (BeWo and HUVEC) cells for our placenta model [25,27,28] (Figure 1). BeWo cells are derived from human placenta and were used to represent syncytiotrophoblasts that form the placenta [32].…”