Protein Corona Formed from Different Blood Plasma Proteins Affects the Colloidal Stability of Nanoparticles Differently

Abstract

Significant progress in the characterization of protein corona has been made. However, insights on how the corona affects the aggregation of nanoparticles (NPs) and consequent biological identity are still lacking. Here, we examined how the corona formed from four major serum proteins, immunoglobulin G (IgG), fibrinogen (FBG), apolipoprotein A1 (ApoA1), and human serum albumin (HSA), over a range of concentrations affects the aggregation of gold NPs (AuNPs). We found that at physiological pH of 7.4, all four proteins aggregated the AuNPs at low concentrations but conferred colloidal stability at high concentrations due to the complete "corona coat" around individual AuNPs. Due to their immune-related functions, IgG and FBG aggregated the AuNPs to a greater extent compared to HSA and ApoA1 which were mostly involved in transport of small molecules. We then introduced the AuNP-corona formed from each protein into an acidic solution at pH 6.2 with high ionic concentration for up to 24 h as a model of the tumor microenvironment to examine for changes in their aggregation. We observed that protein corona formation sterically stabilized the AuNP-corona for all four proteins, resulting in a smaller increase in aggregation and size compared to citratecapped AuNPs. This was especially true for corona formed at high protein:AuNP ratios. Our study therefore showed that the formation of a complete "corona coat" around NPs at sufficiently high protein:NP ratio was required for colloidal stability of designed NP systems in both physiological and cancer microenvironment to maintain efficiency and efficacy in cancer drug delivery.

Identification of physicochemical properties that modulate nanoparticle aggregation in blood

“…Notably, aggregation was observed for medium size CNPs and large CNP at all plasma concentrations tested, while in the case of small CNPs, aggregation was observed only with 10% of plasma, corresponding to the condition used in in vitro tests, but not in vivo. The latter is in agreement with that recently found on Au nanoparticles by Ho and co-workers [42].…”

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

“…Despite PC being considered as normally responsible for NP colloidal instability, recent studies have demonstrated how the protein amount and their nature have a strong effect on NP stability. In the study by Ho et al, AuNPs were incubated with increasing concentrations of HSA, fibrinogen, immunoglobulin, and ApoA1 (Ho et al, 2018). For all these proteins, the particle aggregation had inverse proportion pattern: at lower protein concentrations, all the proteins increased NP aggregation, but at higher concentrations, the NPs appeared to be stabilized.…”

“…• The presence of cell culture medium can influence PC composition. Bonvin et al, 2017Cox et al, 2018Ho et al, 2018…”

Transient coating of γ-Fe2O3 nanoparticles with glutamate for its delivery to and removal from brain nerve terminals

“…Ho et al studied how biomolecules influenced the stability of gold nanoparticles and showed that serum proteins at high concentrations stabilized the nanoparticles, whereas lower concentrations enhanced nanoparticle aggregation. Also, immunoglobulins and fibrinogen caused a greater extent of particle aggregation than other studied proteins [ 27 ]. Zhang et al analyzed the effects of different concentrations of nanoparticles on the zeta potential in serum protein media, and demonstrated that 5% fetal bovine serum can cover almost the whole surface of nanoparticles at a concentration below 500 µg/mL.…”