Size and Surface Functionalization of Iron Oxide Nanoparticles Influence the Composition and Dynamic Nature of Their Protein Corona

Abstract

Nanoparticles (NPs) adsorb proteins when in the biological matrix, and the resulted protein corona could affect NP-cell interactions. The corona has a dynamic nature with the adsorbed proteins constantly exchanging with the free proteins in the matrix at various rates. The rapidly exchanging proteins compose the soft corona, which responds more dynamically to environment changes than the hard corona established by the ones with slow exchange rates. In the present study, the corona formed on the superparamagnetic iron oxide NPs (SPIONs) in human serum was studied by flow field-flow fractionation and ultracentrifugation, which rapidly differentiated the corona proteins based on their exchange rates. By varying the surface hydrophobicity of the SPIONs with a core size around 10 nm, we found out that, the more hydrophobic surface ligand attracted proteins with higher surface hydrophobicity and formed a more dynamic corona with a larger portion of the involved proteins with fast exchange rates. Increasing the core diameter of the SPIONs but keeping the surface ligand the same could also result in a more dynamic corona. A brief investigation of the effect on the cellular uptake of SPIONs using one selected corona protein, transferrin, was conducted. The result showed that, only the stably bound transferrin could significantly enhance cellular uptake, while transferrin bound in a dynamic nature had negligible impact. Our study has led to a better understanding of the relationship between the particle properties and the dynamic nature of the corona, which can help with design of nanomaterials with higher biocompatibility and higher efficacy in biosystems for biomedical applications.

High-Throughput Profiling of Nanoparticle–Protein Interactions by Fluorescamine Labeling

“…Protein hydrophobicity was represented by the grand average of hydropathy (GRAVY) scores calculated using ProtParam, a tool available in the SIB ExPASy Bioinformatics Resources Portal. 25 The selected proteins covered a wide range of Mw (from 11.5 to 300 kDa), pI (from 5.2 to 9.5), hydrophobicity (GRAVY score from -0.004 to -0.885), and number of primary amines (from 17 to 255).…”

Particle Targeting in Complex Biological Media

“…This can be accomplished by having the desired proteins present in the 'hard' corona, which is more stably bound to the particle surface than the 'soft' corona. [167] Moreover, the soft corona needs to be as sufficiently thin so as to not hinder the function of the recruited proteins. [160] Ashby et al observed a relationship between particle properties and the dynamic nature of protein coronas by studying protein exchange rates on the surface of particles with different surface hydrophobicity and core diameter.…”

“…[160] Ashby et al observed a relationship between particle properties and the dynamic nature of protein coronas by studying protein exchange rates on the surface of particles with different surface hydrophobicity and core diameter. [167] Higher surface hydrophobicity or larger core sizes resulted in a more dynamic protein corona with a larger portion of adsorbed proteins exhibiting fast exchange rates. [167] Therefore, both the size and surface hydrophobicity must be carefully controlled to ensure that recruited proteins remain stable and can perform their function in the corona.…”

“…[167] Higher surface hydrophobicity or larger core sizes resulted in a more dynamic protein corona with a larger portion of adsorbed proteins exhibiting fast exchange rates. [167] Therefore, both the size and surface hydrophobicity must be carefully controlled to ensure that recruited proteins remain stable and can perform their function in the corona. In addition, the surface modification of particles also plays an important role in determining the protein corona formation.…”

“…In addition, the surface modification of particles also plays an important role in determining the protein corona formation. [167,168] For particles with various surface functionalities, such as targeting ligands, stealth molecules, and other functional groups to recruit specific proteins, a rational design of all surface functional molecules is necessary for improved particle performance. This includes optimization of surface density, choice of end groups, molecular size and structure, as well as coupling methods of the functional molecules.…”