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，暴露于银纳米颗粒 (AgNP) 的细胞会经历内质网 (ER) 应激，导致细胞凋亡和毒性，然而，AgNP 诱导的内质网应激的基本机制尚不清楚。我们假设 AgNP 和吸附蛋白质之间的生物物理相互作用导致蛋白质错误折叠，从而引发内质网应激反应。我们的研究检查了暴露于 20 或 100 nm AgNP 的大鼠主动脉内皮细胞 (RAEC)，其中有或没有由牛血清白蛋白 (BSA)、高密度脂蛋白 (HDL) 或胎牛血清 (FBS) 组成的生物冠 (BC)，以形成复杂的BC。由 BSA 或 FBS 蛋白组成的 BC 的存在显着减少了 RAEC 中 20 nm 和 100 nm AgNP 的摄取。蛋白质印迹分析表明，尽管 BC 的存在导致摄取减少，但暴露于 20 nm 的 RAEC 中 IREα 和 PERK 通路被强烈激活。100 nm AgNP 没有观察到这一点。高光谱暗视野显微镜定性证实，在 RAEC 摄取后，预形成的 BC 得以维持。透射电子显微镜证明了 AgNP 的亚细胞定位具有尺寸依赖性效应。总体而言，这些结果表明 AgNP 大小、表面积和 BC 形成控制着 ER 应激的诱导和细胞内运输的改变。