The nanoparticle protein corona impacts interactions with monocytes and macrophages.

This study demonstrates that both the presence and the type of the protein corona have a high impact on the interactions of nanoparticles with cells of the mononuclear phagocyte system. Nanoparticles with an opsonin-rich protein corona are rapidly recognized and taken up by these cells. This results in the clearance of nanoparticles from the bloodstream and their accumulation in liver and spleen. To gain deeper insights into this phenomenon, the protein corona was analyzed using mass spectrometry. Furthermore, nanoparticle interactions with THP-1 monocytes and macrophage-like cells derived from THP-1 monocytes were investigated using fluorescence microscopy and flow cytometry. Specifically, we examined the following aspects: (I) the duration of nanoparticle incubation with immune cells, (II) the type of the protein corona formed, (III) the type of immune cells used, and (IV) the medium used for nanoparticle incubation. We demonstrated that the composition of the hard protein corona, and especially the strength of the enrichment of opsonins, is a key determinant of nanoparticle interaction with immune cells, highlighting the importance of protein corona analysis.