Formation of a protein corona on silver nanoparticles mediates cellular toxicity via scavenger receptors

Jonathan H. Shannahan, Ramakrishna Podila, Abdullah A. Aldossari, Hilary Emerson, Brian A. Powell, Pu Chun Ke, Apparao M. Rao, Jared M. Brown

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65 Citations (Scopus)


Addition of a protein corona (PC) or protein adsorption layer on the surface of nanomaterials following their introduction into physiological environments may modify their activity, bio-distribution, cellular uptake, clearance, and toxicity. We hypothesize that silver nanoparticles (AgNPs) will associate with proteins common to human serum and cell culture media forming a PC that will impact cell activation and cytotoxicity. Furthermore, the role of scavenger receptor BI (SR-BI) in mediating this toxicity was evaluated. Citrate-suspended 20 nm AgNPs were incubated with human serum albumin (HSA), bovine serum albumin (BSA), high-density lipoprotein (HDL), or water (control) to form a PC. AgNPs associated with each protein (HSA, BSA, and HDL) forming PCs as assessed by electron microscopy, hyperspectral analysis, ζ-potential, and hydrodynamic size. Addition of the PC decreased uptake of AgNPs by rat lung epithelial and rat aortic endothelial cells. Hyperspectral analysis demonstrated a loss of the AgNP PC following internalization. Cells demonstrated concentration-dependent cytotoxicity following exposure to AgNPs with or without PCs (0, 6.25, 12.5, 25 or 50 μg/ml). All PC-coated AgNPs were found to activate cells by inducing IL-6 mRNA expression. A small molecule SR-BI inhibitor was utilized to determine the role of SR-BI in the observed effects. Pretreatment with the SR-BI inhibitor decreased internalization of AgNPs with or without PCs, and reduced both cytotoxicity and IL-6 mRNA expression. This study characterizes the formation of a PC on AgNPs and demonstrates its influence on cytotoxicity and cell activation through a cell surface receptor.

Original languageEnglish
Pages (from-to)136-146
Number of pages11
JournalToxicological Sciences
Issue number1
Publication statusPublished - 1 Jan 2015
Externally publishedYes


  • darkfield microscopy
  • endothelial cells
  • epithelial cells
  • hyperspectral microscopy
  • in vitro toxicity
  • nanotoxicology

Cite this

Shannahan, J. H., Podila, R., Aldossari, A. A., Emerson, H., Powell, B. A., Ke, P. C., Rao, A. M., & Brown, J. M. (2015). Formation of a protein corona on silver nanoparticles mediates cellular toxicity via scavenger receptors. Toxicological Sciences, 143(1), 136-146.