The “gut” corona at the surface of nanoparticles is dependent on exposure to bile salts and phospholipids

Hypothesis: The formation of a biomolecular corona on nanoparticle surfaces significantly influences their biological behaviour, particularly in drug delivery applications. Despite the prevalence of ingestion of particles (e.g, during oral drug delivery), our understanding of corona formation within the gastrointestinal (GI) tract remains limited, especially for non-protein components. The hypothesis of this work is that the exposure of nanoparticles to bile components will form a “corona” structure and protein corona will represent proteomes different from the original bile fluid. Two major aspects of biomolecular corona formed in GI fluid (hereby termed “gut corona), which ultimately dictate the fate of particle-based carriers, include the composition and the surface structure of nanoparticle-corona complex. Experiments: The structure and composition of the biomolecular corona formed on model SiO₂ nanoparticles within simulated and extracted bile fluids were determined using small-angle scattering, quantification assays, and liquid chromatography with tandem mass spectrometry (LC-MS/MS) techniques. Findings: The formation of raspberry-like structures was identified, with bile micelles adopting ellipsoidal shapes around the nanoparticles, as opposed to a surface covered with a uniform corona (i.e., core–shell structure). Assay quantification and proteomics experiments revealed a notable increase in the ratio of protein to bile salt within the corona compared to the original bile fluid. The composition of the proteome differed between the bovine bile and the protein corona with only 34 proteins associated with the nanoparticles from the top 100 identified in bovine bile. Despite the differences in protein types identified between bovine bile and gut corona, the proportions of protein between different functional classes, such as enzymes and structural proteins, show little variation. This work elucidates the intricate interactions between nanoparticles and gut molecules, offering insights crucial for designing nanoparticle formulations for optimized oral drug delivery and understanding nanoparticle behaviour within the GI tract.