Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA.
School of Health Sciences, College of Health and Human Sciences, Purdue University, West Lafayette, IN 47907, USA.
Ecotoxicol Environ Saf. 2019 Apr 15;170:77-86. doi: 10.1016/j.ecoenv.2018.11.107. Epub 2018 Dec 4.
Prior research has demonstrated cells exposed to silver nanoparticles (AgNPs) undergo endoplasmic reticulum (ER) stress leading to cellular apoptosis and toxicity, however, the fundamental mechanism underlying AgNP-induced ER stress is unknown. We hypothesize the biophysical interactions between AgNPs and adsorbed proteins lead to misfolded proteins to elicit an ER stress response. Our investigation examined rat aortic endothelial cells (RAEC) exposed to 20 or 100 nm AgNPs with or without a biocorona (BC) consisting of bovine serum albumin (BSA), high density lipoprotein (HDL) or fetal bovine serum (FBS) to form a complex BC. The presence of a BC consisting of BSA or FBS proteins significantly reduced uptake of 20 nm and 100 nm AgNPs in RAEC. Western blot analysis indicated robust activation of the IREα and PERK pathways in RAEC exposed to 20 nm despite the reduction in uptake by the presence of a BC. This was not observed for the 100 nm AgNPs. Hyperspectral darkfield microscopy qualitatively confirmed that the preformed BC was maintained following uptake by RAEC. Transmission electron microscopy demonstrated a size dependent effect on the sub-cellular localization of AgNPs. Overall, these results suggest that AgNP size, surface area and BC formation governs the induction of ER stress and alterations in intracellular trafficking.
先前的研究表明，暴露于银纳米粒子（AgNPs）的细胞会经历内质网（ER）应激，导致细胞凋亡和毒性，然而，AgNP 诱导的 ER 应激的基本机制尚不清楚。我们假设 AgNPs 与吸附蛋白之间的生物物理相互作用导致错误折叠的蛋白质引发 ER 应激反应。我们的研究检查了暴露于 20 或 100nm AgNPs 的大鼠主动脉内皮细胞（RAEC），以及是否存在由牛血清白蛋白（BSA）、高密度脂蛋白（HDL）或胎牛血清（FBS）组成的生物被膜（BC），以形成复杂的 BC。BSA 或 FBS 蛋白组成的 BC 的存在显著降低了 RAEC 对 20nm 和 100nm AgNPs 的摄取。Western blot 分析表明，尽管存在 BC 会减少摄取，但暴露于 20nm AgNPs 的 RAEC 中 IREα 和 PERK 途径的活性得到了强烈激活。对于 100nm AgNPs，则没有观察到这种情况。高光谱暗场显微镜定性证实了预形成的 BC 在被 RAEC 摄取后得以维持。透射电子显微镜显示，AgNPs 的大小对其亚细胞定位有尺寸依赖性的影响。总的来说，这些结果表明，AgNP 的尺寸、表面积和 BC 的形成决定了 ER 应激的诱导和细胞内运输的改变。
