Protein Corona Composition of Gold Nanocatalysts

Abstract

The interaction between nanoparticles (NPs) and biological environments is profoundly influenced by a stable, strongly adsorbed "hard" protein corona. This corona significantly determines the NPs' pharmacokinetics and biological destiny. Our study delves into the mechanisms by which colloidal Au nanocrystals that are synthesized electrochemically without surface-capping organic ligands, known as CNM-Au8, traverse the blood-brain barrier (BBB) and target human brain tissue for treating neurodegenerative disorders. We discovered that upon interaction with human plasma, CNM-Au8 gold nanocrystals (AuNCs) effectively attract a variety of crucial apolipoproteins, notably apolipoproteins E, to their surfaces. This interaction likely facilitates their passage through the BBB. Furthermore, the coronas of these AuNCs exhibit a substantial presence of albumin and a notable absence of opsonin-based proteins, contributing to prolonged blood circulation. These characteristics align well with the clinical performance observed for the CNM-Au8 NCs. This study highlights that AuNCs with intentionally engineered structures and surfactant-free surfaces can create a distinct protein corona composition. This finding holds significant promise for the development of advanced therapeutic agents aimed at combating neurodegenerative diseases.

Figure 1

FFF results of CNM-Au8 AuNCs at a concentration of 10 μg/mL, suspended in (A) 6.5 mM NaHCO3 and (B) a buffered solution, which demonstrated an increase in the detected size of NPs indicative of aggregation.

Figure 2

Representative TEM images of CNM-Au8 AuNCs prior to (top panels) and following (bottom panels) protein corona formation, highlighting the corona shell encasing the AuNCs’ surfaces.

Figure 3

Representative AFM height and vertical deflection images showcase the uniform formation of corona-coated CNM-Au8 AuNCs. Insets A and B highlight the out-of-plane height of the selected particles, demonstrating the consistent coating achieved across the AuNCs.

Figure 4

SDS-PAGE analysis of protein corona-coated CNM-Au8 NCs at different concentrations and incubation times. Each row represents images corresponding to replicates.

Figure 5

Percentage of albumin, different fibrinogen types, immunoglobulins, apolipoproteins, and apolipoprotein E in plasma versus protein corona profiles on CNM-Au8 NCs at various concentrations and incubation durations. Each bar represents the average of three separate experiments, each accompanied by its standard deviation. The graph demonstrates significant variations (p < 0.01) in albumin, immunoglobulins, and apolipoproteins when comparing their presence in plasma to their respective concentrations in the protein coronas of CNM-Au8 NCs at all concentrations and time points, underscoring the distinct interaction dynamics between these proteins and CNM-Au8 NCs.