School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou, Jiangsu 215123, China.
CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China; Jinan Guo Ke Medical Technology Development Co. Ltd., Jinan, China.
Aquat Toxicol. 2022 Oct;251:106286. doi: 10.1016/j.aquatox.2022.106286. Epub 2022 Sep 2.
Despite the increasing evidences for adenosine triphosphate-binding cassette (ABC transporters)-mediated efflux of nanoparticles, the universality of these phenomena and the determining factors for the process remained to be clarified. This paper aimed to systemically investigate the role of nanoparticle size in the interactions between adenosine triphosphate-binding cassette (ABC transporters) and gold nanoparticles (AuNPs, 3 nm, 19 nm, and 84 nm, named as Au-3, Au-19, and Au-84) in zebrafish embryos. The results showed that all the three AuNPs induced significant toxicity as reflected by delayed hatching of embryos, decreased glutathione (GSH) contents, and increased reactive oxygen species (ROS) levels. Under the hindrance of embryo chorions, smaller AuNPs could more easily accumulate in the embryos, causing higher toxicity. Addition of transporter inhibitors enhanced the accumulation and toxicity of Au-3 and Au-19, and these nanoparticles induced the expressions of abcc2 and abcb4, indicating a fact that Au-3 and Au-19 were the potential substrates of ABC transporters, but these phenomena were barely found for Au-84. On the contrary, Au-84 suppressed the gene expressions of various ABC transporters like abcc1, abcg5, and abcg8. With specific suppressors, transcription factors like nuclear factor-erythroid 2-related factor-2 (Nrf2) and pregnane X receptor (Pxr) were found to be important in the induction of ABC transporters by AuNPs. After all, these results revealed a vital role of nanoparticle sizes in the interactions between ABC transporters and AuNPs in zebrafish embryos, and the critical size could be around 19 nm. Such information would be beneficial in assessing the environmental risk of nanoparticles, as well as their interactions with other chemical toxicants.
尽管越来越多的证据表明三磷酸腺苷结合盒（ABC）转运蛋白介导了纳米颗粒的外排，但这些现象的普遍性和决定因素仍有待阐明。本文旨在系统研究纳米颗粒尺寸在 ABC 转运蛋白与金纳米颗粒（AuNPs，3nm、19nm 和 84nm，分别命名为 Au-3、Au-19 和 Au-84）在斑马鱼胚胎中的相互作用中的作用。结果表明，所有三种 AuNPs 都表现出明显的毒性，表现为胚胎孵化延迟、谷胱甘肽（GSH）含量降低和活性氧（ROS）水平升高。在胚胎卵壳的阻碍下，较小的 AuNPs 更容易在胚胎中积累，导致更高的毒性。转运蛋白抑制剂的添加增强了 Au-3 和 Au-19 的积累和毒性，这些纳米颗粒诱导了 abcc2 和 abcb4 的表达，表明 Au-3 和 Au-19 是 ABC 转运蛋白的潜在底物，但这些现象在 Au-84 中几乎没有发现。相反，Au-84 抑制了各种 ABC 转运蛋白如 abcc1、abcg5 和 abcg8 的基因表达。使用特定的抑制剂，发现转录因子如核因子-红细胞 2 相关因子-2（Nrf2）和孕烷 X 受体（Pxr）在 AuNPs 诱导 ABC 转运蛋白中起着重要作用。总之，这些结果揭示了纳米颗粒尺寸在 ABC 转运蛋白与斑马鱼胚胎中 AuNPs 相互作用中的重要作用，关键尺寸可能在 19nm 左右。这些信息将有助于评估纳米颗粒的环境风险，以及它们与其他化学毒物的相互作用。
