Serum proteins on nanoparticles: early stages of the "protein corona".

Nanoparticles in biological systems such as the bloodstream are exposed to a complex solution of biomolecules. A "corona" monolayer of proteins has historically been thought to form on nanoparticles upon introduction into such environments. To examine the first steps of protein binding, Fluorescence Correlation/Cross Correlation Spectroscopy and Fluorescence Resonance Energy Transfer were used to directly analyze four different nanoparticle systems. CdSe/ZnS core/shell quantum dots, 100 nm diameter polystyrene fluospheres, 200 nm diameter polystyrene fluospheres, and 200 nm diameter PEG-grafted DOTAP liposomes were studied with respect to serum protein binding, using bovine serum albumin as a model. Surface heterogeneity is found to be a key factor in protein binding to these nanoparticles, and as such we present a novel conceptualization of the early hard corona as low-ratio, non-uniform binding rather than a uniform monolayer.