Nanoparticles have important biological and biomedical applications ranging from drug and gene delivery to biosensing.
In the presence of extracellular proteins, a “corona” of proteins adsorbs on the surface of the nanoparticles, altering their
interaction with cells, including immune cells. Nanoparticles are often functionalized with polyethylene glycol (PEG) to
reduce this non-specific adsorption of proteins. To understand the change in protein corona that occurs following
PEGylation, we first quantified the adsorption of blood serum proteins on bare and PEGylated gold nanoparticles using
gel electrophoresis. We find a threefold decrease in the amount of protein adsorbed on PEGylated gold nanoparticles
compared to the bare gold nanoparticles, showing that PEG reduces, but does not prevent, corona formation. To
determine if the secondary structure of corona proteins was altered upon adsorption onto the bare and PEGylated gold
nanoparticles, we use CD spectroscopy to characterize the secondary structure of bovine serum albumin following
incubation with the nanoparticles. Our results show no significant change in protein secondary structure following
incubation with bare or PEGylated nanoparticles. Further examination of the secondary structure of bovine serum
albumin, α2-macroglobulin, and transferrin in the presence of free PEG showed similar results. These findings provide
important insights for the use of PEGylated gold nanoparticles under physiological conditions.