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Ecotoxicol Environ Saf. 2019 Apr 15;170:77-86. doi: 10.1016/j.ecoenv.2018.11.107. Epub 2018 Dec 4.

Biocorona formation contributes to silver nanoparticle induced endoplasmic reticulum stress.

Author information

1
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA.
2
School of Health Sciences, College of Health and Human Sciences, Purdue University, West Lafayette, IN 47907, USA.
3
Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA; Clemson Nanomaterials Center and COMSET, Clemson University, Anderson, SC 29625, USA.
4
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA. Electronic address: jared.brown@ucdenver.edu.

Abstract

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.

KEYWORDS:

AgNP; ER stress; Hyperspectral imaging; Nanoparticle toxicity; Nanotoxicology; Protein corona

PMID:
30529623
PMCID:
PMC6331260
[Available on 2020-04-15]
DOI:
10.1016/j.ecoenv.2018.11.107
[Indexed for MEDLINE]

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