title: Mechanisms of cell uptake, inflammatory potential and protein corona effects with gold nanoparticles.
abstract: OBJECTIVE
  To assess inflammation, cellular uptake and endocytic mechanisms of gold nanoparticles (AuNP) in human epidermal keratinocytes with and without a protein corona.
  
  
  METHODS
  Human epidermal keratinocytes were exposed to 40 and 80 nm AuNP with lipoic acid, polyethylene glycol (PEG) and branched polyethyleneimine (BPEI) coatings with and without a protein corona up to 48 h. Inhibitors were selected to characterize endocytosis.
  
  
  CONCLUSIONS
  BPEI-AuNP showed the greatest uptake, while PEG-AuNP had the least. Protein coronas decreased uptake and affected their mechanism. AuNP uptake was energy-dependent, except for 40 nm lipoic-AuNP. Most AuNP were internalized by clathrin and lipid raft-mediated endocytosis, except for 40 nm PEG was by raft/noncaveolae mediated endocytosis. Coronas inhibited caveolae-mediated-endocytosis with lipoic acid and BPEI-AuNP and altered 40 nm PEG-AuNP from raft/noncaveolae to clathrin. Inflammatory responses decreased with a plasma corona. Results suggest protein coronas significantly affect cellular uptake and inflammatory responses of AuNP.
authors.affiliation: Nanotechnology Innovation Center of Kansas State University (NICKS), Kansas State University, Manhattan, KS, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Nanotechnology Innovation Center of Kansas State University (NICKS), Kansas State University, Manhattan, KS, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Monteiro-Riviere
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects*; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D000066970:Protein Corona / Q000378:metabolism*; D008063:Thioctic Acid / Q000737:chemistry
chemical_list: D001798:Blood Proteins; D000066970:Protein Corona; D011092:Polyethylene Glycols; D008063:Thioctic Acid; D006046:Gold; D011094:Polyethyleneimine
keywords: endocytosis; gold nanoparticles; human epidermal keratinocytes; inflammation; mechanisms of cellular uptake; protein corona