Understanding the Influence of a Bifunctional Polyethylene Glycol Derivative in Protein Corona Formation around Iron Oxide Nanoparticles

Abstract

Superparamagnetic iron oxide nanoparticles are one of the most prominent agents used in theranostic applications, with MRI imaging the main application assessed. The biomolecular interface formed on the surface of a nanoparticle in a biological medium determines its behaviour in vitro and in vivo. In this study, we have compared the formation of the protein corona on highly monodisperse iron oxide nanoparticles with two different coatings, dimercaptosuccinic acid (DMSA), and after conjugation, with a bifunctional polyethylene glycol (PEG)-derived molecule (2000 Da) in the presence of Wistar rat plasma. The protein fingerprints around the nanoparticles were analysed in an extensive proteomic study. The results presented in this work indicate that the composition of the protein corona is very difficult to predict. Proteins from different functional categories—cell components, lipoproteins, complement, coagulation, immunoglobulins, enzymes and transport proteins—were identified in all samples with very small variability. Although both types of nanoparticles have similar amounts of bonded proteins, very slight differences in the composition of the corona might explain the variation observed in the uptake and biotransformation of these nanoparticles in Caco-2 and RAW 264.7 cells. Cytotoxicity was also studied using a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Controlling nanoparticles’ reactivity to the biological environment by deciding on its surface functionalization may suggest new routes in the control of the biodistribution, biodegradation and clearance of multifunctional nanomedicines.

Pharmacokinetics of magnetic iron oxide nanoparticles for medical applications

“…Undoubtedly, in order to rationally design nanoparticles for medical applications, it is necessary to understand the mechanism of formation of the protein corona and its composition. Ruiz et al [ 31 ] investigated, by means of proteomic analysis, the formation and composition of the protein corona around magnetic nanoparticles coated in two ways: in the first case using dimercaptosuccinic acid (DMSA), and in the other – by means of a diamine (PEG)-derived molecule (2000 Da) which is widely used for providing a long circulation time [ 32 , 33 ]. Semiquantitative analysis of the protein corona composition of the above-mentioned nanoparticles is shown in Fig.…”

Magnetic nanoparticles in regenerative medicine: what of their fate and impact in stem cells?

“…Indeed, in vivo the nanoparticles are in contact with biological fluids and, immediately after injection, they interact with the plasma proteins (opsonins) which results in the adsorption of these proteins on their surface. This process, named opsonization, will take place at different rates depending on the nanoparticle features, particularly its coating nature [161,162]. Toxicology results obtained in vivo in diverse animal models (e.g.…”

Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

“…Despite nearly identical magnetite core size, hydrodynamic size, and zeta potential of the MNPs in the stock solution, the hydrodynamic size of PEG-SO-MNPs in culture medium was almost three times that of BSA-SO-MNPs (281 nm vs 98 nm, respectively) due to absorption of serum proteins on the particle surface [ 40 ]. Although PEGylation decreases the protein absorption on the particle surface, it does not completely prevent it [ 41 ]. BSA is a component of serum proteins and commonly involved in PC formation.…”