The critical role of nanoparticle sizes in the interactions between gold nanoparticles and ABC transporters in zebrafish embryos

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.