Toward Diffusion Measurements of Colloidal Nanoparticles in Biological Environments by Nuclear Magnetic Resonance.

Protein corona formation on the surface of nanoparticles (NPs) is observed in situ by measuring diffusion coefficients of the NPs under the presence of proteins with a 19 F nuclear magnetic resonance (NMR) based methodology. Formation of a protein corona reduces the diffusion coefficient of the NPs, based on an increase in their effective hydrodynamic radii. With this methodology it is demonstrated that the apparent dissociation constant of protein-NP complexes may vary over at least nine orders of magnitude for different types of proteins, in line with the Vroman effect. Using this methodology, the interaction between one type of protein and one type of nanoparticle can be studied quantitatively. Due to the NMR-based detection, this methodology has no interference by absorption/scattering effects, by which optical detection schemes are affected. By using the potential of the NMR chemical shift, the detection of multiple 19 F signals simultaneously opens the possibility to study the diffusion of several NPs at the same time. The 19 F labeling of the NPs has negligible effect on their acute toxicity and moderate effect on NPs uptake by cells.