Beyond Unpredictability: The Importance of Reproducibility in Understanding the Protein Corona of Nanoparticles

Abstract

While it is well established that the surface of a nanoparticle plays a pivotal role for the protein corona, the vast number of proteins present in biological media render general conclusions about affinities between nanoparticle surfaces and proteins nontrivial. Recently published articles increasingly reveal differences between systems and an ever increasing number of influencing factors for the protein corona. In contrast, the present study posits that the reported differences may, at least in part, be due to poor experimental design, which leads to biased results. The present study investigates protein adsorption onto silica nanoparticles with different chemical groups on the surface by the statistical analysis of triplicate measurements as well as control measurements. We demonstrate that 60% of the identified protein types did not have any significant affinities for the nanoparticles. Of the remaining 40%, 60% were driven by surface charges and only 40% preferentially adsorbed onto specific surface groups. Furthermore, we found that of the 20 most abundant proteins in the serum, only five bound to the nanoparticles studied here. We illustrate the importance of control replicate experiments to avoid exaggerated differences between systems and to properly quantify the differences and similarities between comparable systems.

Protein Corona Composition of Silica Nanoparticles in Complex Media: Nanoparticle Size does not Matter

“…Thus, the size factor appears to be less determinant for protein corona composition than previously reported [24,36]. Recently, the importance of an ever-increasing number of determinant factors for the protein corona has been questioned [76]. It appeared that even very important factors such as surface chemical groups may not be as determinant as what one could assume.…”

Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles

“…REPES analysis of the PMPC-PVBTMA system shows the growth of~200 nm aggregates over 1 to 10 h. This slight stability issue may be mitigated by increasing the degree of polymerization of PMPC, as the total length of the zwitterionic corona in micelles were previously shown to affect nanoparticle stabilization and delivery efficacy [33]. Nevertheless, because protein adsorption onto nanoparticle carriers in biological settings is a known design consideration for micelle assemblies [65,66], the prepared PCMs and zPCM show good overall resistance to destabilization by serum.…”

Theranostic Approach for the Protein Corona of Polysaccharide Nanoparticles

“…Other proteins form a dynamic layer based on the Vroman effect – high‐abundance, low‐affinity proteins are dynamically replaced by lower‐abundance higher‐affinity proteins overtime during the nano‐bio interaction [46] . Conformational changes of the adsorbed protein can result from surface curvature, topography and surface energy/hydrophobicity [47] . It has also been shown that PC composition varies depending on the environment [42,43] .…”

“…[46] Conformational changes of the adsorbed protein can result from surface curvature, topography and surface energy/hydrophobicity. [47] It has also been shown that PC composition varies depending on the environment. [42,43] New studies on carbohydrate nanopolymers are beginning to routinely involve PC analysis using gel electrophoresis or mass spectrometry (MS) analysis.…”