Impact of protein-nanoparticle interactions on gastrointestinal fate of ingested nanoparticles: Not just simple protein corona effects

The interaction of nanoparticles (NPs) with proteins in their surroundings is a key factor determining their biological fate. The formation of a protein corona around ingested NPs in complex food matrices and in the gastrointestinal tract (GIT) is known to impact their gastrointestinal fate. In this study, the interaction between titanium dioxide (TiO2) NPs from a common food additive (E171) and casein, an abundant milk protein was characterized. The impact of these interactions on the potential gastrointestinal fate of the NPs was examined using a simulated GIT model. Our results showed that a series of complex molecular events occurred when the TiO2 NPs were added to casein solutions, including dissociation of casein micelles, NP-protein complex formation, and complex aggregation. Extensive aggregation was observed under conditions where charge neutralization occurred, which was attributed to a reduction in the electrostatic repulsion between the NP-protein complexes and to a polymer bridging effects. There was a pronounced decrease in the rate and extent of gastric digestion of the casein in the presence of the TiO2 NPs, indicating that complex formation reduced the access of pepsin to the peptide bonds. These findings stress the importance of taking into account the interactions of ingested NPs with food matrix and gastrointestinal components. Moreover, our findings show that the simple concept of a protein corona does not adequately explain the complex structural changes that occur when proteins and NPs interact.