Rapid Formation of Plasma Protein Corona Critically Affects Nanoparticle Pathophysiology
Stefan Tenzer, Dominic Docter, Jörg Kuharev, Anna Musyanovych, Verena Fetz, Rouven Hecht, Florian Schlenk, Dagmar Fischer, Klytaimnistra Kiouptsi, Christoph Reinhardt, Katharina Landfester, Hansjörg Schild, Michael Maskos, Shirley K. Knauer, Roland H. Stauber
Abstract
Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time. Collectively, depending on the individual biological characteristics of the respective cell type studied, clearly the rapid formation of the plasma protein corona is capable of kinetically modulating distinct pathophysiological effects. A functionally diverse group of plasma proteins highly enriched in the coronas of silica nanoparticles are the apolipoproteins, involved in lipid and cholesterol transport. To allow a snapshot resolution of the corona evolution, particles were incubated with human plasma for different time periods and centrifuged through a sucrose cushion, which allowed the rapid separation of unbound plasma as well as recovery of nanoparticle–corona complexes. Protein binding visualized by gel electrophoresis demonstrated that a complex protein corona was established even at the earliest exposure time point for all nanoparticles examined.