Nanoparticle-Protein Interaction: Demystifying the Correlation between Protein Corona and Aggregation Phenomena.

Protein corona formation and nanoparticles' aggregation have been heavily discussed over the past years since the lack of fine-mapping of these two combined effects has hindered the targeted delivery evolution and the personalized nanomedicine development. We present a multitechnique approach that combines dynamic light and small-angle X-ray scattering techniques with cryotransmission electron microscopy in a given fashion that efficiently distinguishes protein corona from aggregates formation. This methodology was tested using ∼25 nm model silica nanoparticles incubated with either model proteins or biologically relevant proteomes (such as fetal bovine serum and human plasma) in low and high ionic strength buffers to precisely tune particle-to-protein interactions. In this work, we were able to differentiate protein corona, small aggregates formation, and massive aggregation, as well as obtain fractal information on the aggregates reliably and straightforwardly. The strategy presented here can be expanded to other particle-to-protein mixtures and might be employed as a quality control platform for samples that undergo biological tests.

Effect of particle functionalization and solution properties on the adsorption of bovine serum albumin and lysozyme onto silica nanoparticles.

Silica nanoparticles present an enormous potential as controlled drug delivery systems with high selectivity towards diseased cells. This application is directly related to the phenomenon of protein corona, characterized by the spontaneous adsorption of proteins on the nanoparticle surface, which is not fully understood. Here, we report an investigation on the influence of pH, ionic strength and temperature on the thermodynamics of interaction of bovine serum albumin protein (BSA) with non-functionalized silica nanoparticles (SiO2NPs). Complementary, we also investigated the ability of polyethylene glycol (PEG) and zwitterionic sulfobetaine (SBS) surface-modified nanoparticles to prevent the adsorption of BSA (protein negatively charged at physiological pH) and lysozyme (protein positively charged at physiological pH). We showed that BSA interaction with SiO2NPs is enthalpically governed. On the other hand, functionalization of silica nanoparticles with PEG and SBS completely prevented BSA adsorption. However, these functionalized nanoparticles presented a negative zeta potential and were not able to suppress lysozyme anchoring due to strong nanoparticle-protein electrostatic attraction. Due to the similarity of BSA with Human Serum Albumin, this investigation bears a resemblance to processes involved in the phenomenon of protein corona in human blood, producing information that is relevant for the future biomedical use of functionalized nanoparticles.