Translocation of Engineered Nanomaterials across the Placenta-on-a-chip (TENAP)

鉴于工程纳米材料（ENM）在化妆品和个人护理产品中的广泛使用，以及自2009年以来禁止对化妆品成分进行动物试验的事实，人们对ENM对公众健康的潜在不利影响表示担忧，特别是对弱势风险群体，包括孕妇及其发育中的胎儿。最近的流行病学研究表明，怀孕期间接触颗粒物较多与围产期死亡率、早产和出生体重不足的发生率增加有关。胎儿毒性的可能性部分取决于颗粒从母体到胎儿的通道，由胎盘屏障（PB）决定。然而，关于ENM穿过PB的运输及其对生长中的胎儿的影响的研究还处于起步阶段。目前，有三个关键问题与这种不确定性有关：（1）什么条件有利于ENM穿过PB？这很可能与ENM的物理化学性质有关，但目前的理解有限且不确定，主要是由于ENM表征数据不足、研究描述不完整或实验条件不同等原因。(2)ENM在PB内和PB外的命运是什么（即，ENM在穿过PB后的沉积、移位和转化）？(3)移位的ENM是否可能导致胎儿毒性作用？考虑到PB中ENM积累可能较低的可能性，将系统中的ENM定位将是一项具有挑战性的任务，特别是对于PB中具有高元素背景的ENM。因此，迫切需要新的方法，使我们的理解取得突破的能力，ENMs跨越PB和跟踪其影响超越。TENAP项目建议将新型标记技术与胎盘芯片模型相结合，从而实现一种独特的新方法来评估ENM的PB渗透能力以及易位ENM对胎儿的影响。

Given the widespread use of engineered nanomaterials (ENMs) in cosmetics and personal care products, and the fact that animal testing of cosmetics ingredients has been banned since 2009, there are legitimate concerns about the potential adverse effects of ENMs on public heath, especially for vulnerable risk groups including pregnant women and their developing foetuses. Recent epidemiological studies have linked higher particulate matter exposure during pregnancy to increased incidences of perinatal mortality, preterm birth and low birth weight. The potential for foetal toxicity partly depends on the passage of particles from the mother to the foetus, determined by the placental barrier (PB). However, esearch on transport of ENMs across the PB and their effects on the growing foetus is very much in its infancy. Currently, three key questions pertain to this uncertainty: (1) What conditions favour ENMs crossing the PB? This is most likely related to the physicochemical properties of the ENMs but the current understanding is limited and inconclusive, primarily due to insufficient ENM characterization data, incomplete study descriptions, or different experimental conditions, among others. (2) What is the fate of ENMs within and beyond the PB (i.e. the deposition, translocation, and transformation of ENMs after crossing the PB)? (3) Can translocated ENMs potentially cause foetotoxic effects? Given the possibility that the accumulation of ENMs in PB might be low, localizing the ENMs in the system would be a challenging task, especially for ENMs with high elemental backgrounds in the PB. Thus, novel approaches are urgently needed to enable a breakthrough in our understanding of the ability of ENMs to cross the PB and trace their effects beyond. The project TENAP proposes combining novel labelling techniques with a placenta-on-a-chip model enabling a uniquely novel approach to assess the PB-penetration ability of ENMs and effects of translocated ENMs on the foetuses.