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

工程纳米材料在胎盘芯片上的易位 (TENAP)

• 批准号: EP/Y014936/1
• 负责人: Zhiling Guo
• 金额: $ 25.55万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY014936%2F1
• 关键词: Translocation; Engineered; Nanomaterials; across; Placenta

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.

鉴于在化妆品和个人护理产品中广泛使用了工程纳米材料（ENM），并且自2009年以来，对化妆品成分的动物测试已被禁止，因此人们对ENM对公共Heath的潜在不利影响，尤其是对于包括孕妇及其发育不良的胎儿在内的易受伤害的风险群体的潜在不利影响。最近的流行病学研究已将怀孕期间较高的颗粒物暴露与围产期死亡率，早产和低出生体重的发病率增加有关。胎儿毒性的潜力部分取决于颗粒从母亲到胎儿的通过，这是由胎盘屏障（PB）确定的。但是，有关ENM跨PB的运输及其对生长胎儿的影响的研究非常起步。目前，三个关键问题与这种不确定性有关：（1）哪些条件有利于ENMS穿越PB？这很可能与ENM的物理化学特性有关，但是当前的理解是有限且尚无定论的，这主要是由于ENM表征数据不足，研究描述不完整或不同的实验条件等。 （2）ENM的命运在PB内外（即越过Pb后的沉积，易位和转换）？ （3）易位的ENM是否可能引起毒素毒性作用？鉴于ENM在PB中的积累可能很低，因此将ENM定位在系统中是一项具有挑战性的任务，尤其是对于PB中具有较高元素背景的ENM而言。因此，迫切需要采取新颖的方法，以使我们对ENM的能力越过PB并追踪其效果的能力取得突破。该项目TENAP提出了将新型标记技术与芯片上的胎盘模型相结合的，从而实现了一种独特的新方法，以评估ENM的PB渗透能力以及转运ENM对胎儿的影响。