Splenic response to protein corona of nanoparticles in vivo

Abstract

The spleen is a meeting point between antigens transported by the blood stream and the immune apparatus responsible for mounting the host response. However, the interactions between nanomaterials and the spleen, significantly influenced by the protein corona formed on the surface of nanomaterials, are often overlooked. To address this issue, Fe₃O₄ nanoparticles with two distinct surface coatings, i.e., diphosphonate-polyethylene glycol (DP-PEG), and diphosphonate-ε-aminocaproic acid (DP-EACA), were selected for a comprehensive investigation into the impacts of protein corona on the immune response within the spleen, attempting to gain a deeper understanding on how protein corona disturbs the immune response in the spleen to enrich the knowledge about the surface chemistry of nanoparticles. Additionally, carboxymethyl dextran (CM-DEX)-modified Fe₃O₄ nanoparticles, a generic form of the clinically used nanodrug Ferumoxytol, were chosen as a reference. The protein adsorption and its impacts on immune cells, gene expression, and metabolites in the spleen were investigated over a 28-day period. Our findings indicated that the opsonins carried by Fe₃O₄ nanoparticles were strongly correlated with immune response and metabolic disturbances in the spleen. However, DP-PEG coating exhibited remarkable resistance against protein adsorption and minimized spleen perturbation, highlighting its outstanding potential for clinical applications. All these findings are believed very valuable for developing clinically translatable drugs based on nanomaterials.