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

鉴于工程纳米材料在化妆品和个人护理产品中的广泛使用，以及自2009年起禁止对化妆品成分进行动物测试，人们有理由关注工程纳米材料对公众健康的潜在不利影响，特别是对脆弱的风险群体，包括孕妇及其发育中的胎儿。最近的流行病学研究表明，孕期接触更高的颗粒物与围产期死亡、早产和低出生体重的发生率增加有关。对胎儿的潜在毒性部分取决于由胎盘屏障(PB)决定的粒子从母亲进入胎儿的途径。然而，环烯烃类物质的跨PB运输及其对生长中胎儿的影响的研究还处于起步阶段。目前，与这种不确定性有关的三个关键问题是：(1)哪些条件有利于新兴市场跨越大洋彼岸？这很可能与ENM的物理化学性质有关，但目前的理解是有限的和不确定的，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。(2)ENM在PB内外的命运如何(即，ENM在穿过PB后的沉积、转移和转化)？(3)移位的ENM是否可能引起胎毒效应？考虑到在PB中ENM的积累量可能很低，在系统中定位ENM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，迫切需要新的方法来突破我们对ENM跨越PB并追踪其影响的能力的理解。TENAP项目建议将新的标记技术与芯片上胎盘模型相结合，从而实现一种独特的新方法来评估ENM的PB穿透能力和移位的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.