PEGylated nanoparticles: protein corona and secondary structure

Abstract

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.

Protein Corona in Response to Flow: Effect on Protein Concentration and Structure

“…The subsequent interaction of the immune system with NPs is mediated by a layer of blood serum proteins that adsorb on the NP surface during circulation. This opsonization, resulting in a ''corona'' of proteins on the NP surface (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), can be decreased by PEGylation, but complete inhibition remains a challenge (16)(17)(18)(19)(20)(21)(22). The protein corona, described as either a ''hard'' corona of tightly bound proteins or a ''soft'' corona of dynamic, weakly bound proteins (23)(24)(25)(26), has been studied extensively as a function of NP diameter, composition, and surface functionalization (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Protein Corona Analysis of Silver Nanoparticles Exposed to Fish Plasma

“…7–11 For example, PC composition can promote or deter the interaction of NPs with outer membrane receptors for specific cell uptake, 12, 13 or impact their blood circulation lifetime. 14, 15…”

Controlling evolution of protein corona: a prosperous approach to improve chitosan-based nanoparticle biodistribution and half-life

“…Here, not only amount of adsorbed protein, but also type and configuration of them must be considered since they determine the fate of nanoparticles by opsonization 10,12,13 . To attain longer half-life for nano scale delivery systems, the most prevalent strategy is to cover the surface of nanoparticles by some polymers such as polyethylene glycol (PEG) [14][15][16] , poloxamer 17 , and dextran 18,19 . Gref et al fabricated a series of PEG-coated poly lactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA) and poly ε-caprolactone (PCL) nanoparticles with different molecular weights (Mw) of PEG, and showed that adsorption of plasma proteins to the nanoparticles depends on PEG size and content 20 .…”