Protein corona-induced modification of silver nanoparticle aggregation in simulated gastric fluid

Abstract

Due to their widespread incorporation into a range of biomedical and consumer products, the ingestion of silver nanoparticles (AgNPs) is of considerable concern to human health. However, the extent to which AgNPs will be modified within the gastric compartment of the gastrointestinal tract is still poorly understood. Studies have yet to fully evaluate the extent of physicochemical changes to AgNPs in the presence of biological macromolecules, such as pepsin, the most abundant protein in the stomach, or the influence of AgNPs on protein structure and activity. Herein, AgNPs of two different sizes and surface coatings (20 and 110 nm, citrate or polyvinylpyrrolidone) were added to simulated gastric fluid (SGF) with or without porcine pepsin at three pHs (2.0, 3.5, and 5.0), representing a range of values between preprandial (fasted) and postprandial (fed) conditions. Rapid increases in diameter were observed for all AgNPs, with a greater increase in diameter in the presence of pepsin, indicating that pepsin facilitated AgNPs aggregation. AgNPs interaction with pepsin only minimally reduced the protein’s proteolytic functioning capability, with the greatest inhibitory effect caused by smaller (20 nm) particles of both coatings. No changes in pepsin secondary structural elements were observed for the different AgNPs, even at high particle concentrations. This research highlights the size-dependent kinetics of nanoparticle aggregation or dissolution from interaction with biological elements such as proteins in the gastrointestinal tract. Further, these results demonstrate that, in addition to mass, knowing the chemical form and aggregation state of nanoparticles is critical when evaluating toxicological effects from nanoparticle exposure in the body.

The Food Matrix and the Gastrointestinal Fluids Alter the Features of Silver Nanoparticles

“…This is in agreement with other studies that also mentioned the clustering of AgNPs submitted to a gastric digestion. [36,41,42,47] AgNPs agglomeration was also detected by UV-vis spectroscopy in line with published results. [36,47,51] Indeed, UV-vis spectroscopy allows to distinguish dissolution from agglomeration of AgNPs.…”

“…However, most studies focusing on the impact of AgNPs on intestinal cells were performed with pristine nanoparticles (NPs), [26][27][28][29][30][31][32][33] i.e., nanoparticles directly purchased from manufacturer or synthesized in the laboratory. [34] These experiments do not consider their interaction with food components and the potential alterations occurring in the gastrointestinal tract, [35][36][37] while it has been shown that AgNPs can be affected by the surrounding conditions. [38] Due to their high reactivity, NMs might interact with food components, such as carbohydrates, lipids, proteins, and minerals, which may influence their size, charge, agglomeration state, and surface composition.…”

Oral delivery of nanoparticles - let’s not forget about the protein corona

“…Nanotechnologists in the field of food sciences have started to acknowledge the importance of PC on the fate and toxicity of ingested food-grade NPs [8]. It has been shown that incubation of silver NPs in simulated gastric media containing pepsin can result in the formation of PC, which facilitates NP aggregation [9,10]. Similarly, PC can also build upon the surface of polystyrene NPs exposed to various digestive enzymes [11].…”

Food‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood‐testis barrier disruption in mice

“…To simulate the behavior of E171 into the intestinal tract we used two solutions that simulate gastric and intestinal fluids. Briefly, simulated gastric fluid (SGF) contained 80 m m HCl and 34 m m NaCl (Sigma‐Aldrich) in a final volume of 1 L of distilled water and pH 1.1 (Ault et al, ). Simulated intestinal fluid (SIF) contained 60 m m KH 2 PO 4 and 20 m m NaOH in distilled water in a final volume of 1 L with pH 6.8 (Stippler, Sabine, & Jennifer, ).…”