a Institute of Environmental Sciences (CML), Leiden University , Leiden , The Netherlands.
b Center for the Safety of Substances and Products National Institute of Public Health and the Environment , Bilthoven , The Netherlands.
Nanotoxicology. 2019 May;13(4):558-571. doi: 10.1080/17435390.2018.1564079. Epub 2019 Feb 4.
Important questions raised in (nano)ecotoxicology are whether biodistribution of nanoparticles (NPs) is affected by particle shape and to what extent local adverse responses are subsequently initiated. For nanomedicine, these same questions become important when the labeled NPs lose the labeling. In this study, we investigated the biodistribution patterns of gold nanoparticles (AuNPs) as well as immune-related local and systemic sublethal markers of exposure and behavioral assessment. Hatched zebrafish embryos were exposed to four differently shaped non-coated AuNPs with comparable sizes: nanospheres, nanorods, nano-urchins, and nano-bipyramids. Shape-dependent trafficking of the particles resulted in a different distribution of the particles over the target organs. The differences across the distribution patterns indicate that the particles behave slightly different, although they eventually reach the same target organs - yet in different ratios. Mainly local induction of the immune system was observed, whereas systemic immune responses were not clearly visible. Macrophages were found to take AuNPs from the body fluid, be transferred into the veins and transported to digestive organs for clearance. No significant behavioral toxicological responses in zebrafish embryos were observed after exposure. The trafficking of the particles in the macrophages indicates that the particles are removed via the mononuclear phagocytic system. The different ratios in which the particles are distributed over the target organs indicate that the shape influences their behavior and eventually possibly the toxicity of the particles. The observed shape-dependent biodistribution patterns might be beneficial for shape-specific targeting in nanomedicine and stress the importance of incorporating shape-features in nanosafety assessment.
(纳米)生态毒理学中提出的重要问题是纳米颗粒(NPs)的生物分布是否受颗粒形状的影响,以及随后会在多大程度上引发局部不良反应。对于纳米医学,当标记的 NPs 失去标记时,同样的问题也变得重要。在这项研究中,我们研究了金纳米颗粒(AuNPs)的生物分布模式,以及免疫相关的局部和全身亚致死暴露标记物和行为评估。孵育的斑马鱼胚胎暴露于四种具有相似尺寸但形状不同的非涂层 AuNPs:纳米球、纳米棒、纳米刺和纳米双锥体。颗粒的形状依赖性运输导致颗粒在靶器官中的分布不同。分布模式的差异表明,尽管颗粒最终到达相同的靶器官,但它们的行为略有不同,尽管它们的比例不同。主要观察到免疫系统的局部诱导,而全身免疫反应不明显。发现巨噬细胞从体液中摄取 AuNPs,转移到静脉中,并运送到消化器官进行清除。暴露后未观察到斑马鱼胚胎出现明显的行为毒性反应。颗粒在巨噬细胞中的运输表明,颗粒通过单核吞噬细胞系统被清除。颗粒在靶器官中的分布比例不同表明,形状会影响它们的行为,最终可能会影响颗粒的毒性。观察到的形状依赖性生物分布模式可能有利于纳米医学中的特异性靶向,并强调在纳米安全性评估中纳入形状特征的重要性。