Corona interactome: a key for deciphering protein adsorption kinetics on silica nanocarriers

Magnetic mesoporous silica nanoparticles (M-MSNs) represent promising targeting tools for cancer diagnostic and therapy. In biological systems, nanoparticles interact with proteins and form a layer named "corona" that drives... [ view full abstract ]

Magnetic mesoporous silica nanoparticles (M-MSNs) represent promising targeting tools for cancer diagnostic and therapy. In biological systems, nanoparticles interact with proteins and form a layer named "corona" that drives their biological fate and toxicity. The corona around NP creates a new nano-object, whose interactions with living cells are different from those induced by the pristine NPs. We have investigated the behavior of adsorbed proteins around M-MSNs with two biological fluids, fetal bovine and human sera. The first one is interesting for in vitro toxicology and the second for in vivo diagnosis and therapy. Thereby, after a quantification of protein adsorption on these M-MSNs by BCA assay over time, we qualified these adsorbed proteins by high throughput comparative proteomics during long term kinetics. We observed an increase of the protein layer with both serum types from 30 seconds to 7 days of contact by both techniques. During this kinetics, the growth of the protein corona began instantly after NP immersion. We thus detected 90 to 128 and 134 to 153 distinct adsorbed proteins for the bovine and human corona, respectively. By using computational biology tools and protein-protein interaction databases, we have highlighted three major clusters of protein behavior in contact with nanoparticles. We demonstrated precisely how the protein network builds up within the corona during the experimental kinetics resulting in a multiparametric representation of the “corona interactome”. This original approach may allow understanding how NPs interact with biological fluids and provide some clues for the design of stealth nanocarriers.