Impact of serum proteins on MRI contrast agents: cellular binding and T₂relaxation

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) used as MRI contrast agents or for theranostic applications encounter a complex mixture of extracellular proteins that adsorb on the SPION surface forming a protein corona. Our goal was to understand how cellular binding and T2 relaxation times are affected by this protein corona. Our studies focused on carboxymethyl dextran-modified SPIONs, chosen for their similarity to Resovist SPIONs used to detect liver lesions. Using a combination of fluorescence microscopy and flow cytometry, we find that the cellular binding of SPIONs to both macrophages and epithelial cells is significantly inhibited by serum proteins. To determine if this decreased binding is due to the iron oxide core or the carboxymethyl dextran surface coating, we functionalized polystyrene nanoparticles with a similar carboxymethyl dextran coating. We find a comparable decrease in cellular binding for the carboxymethyl dextran-polystyrene nanoparticles indicating that the carbohydrate surface modification is the key factor in SPION-cell interactions. NMR measurements showed that T2 relaxation times are not affected by corona formation. These results indicate that SPIONs have a decreased binding to cells under physiological conditions, possibly limiting their use in theranostic applications. We expect these results will be useful in the design of SPIONs for future diagnostic and therapeutic applications.

The biocorona: a challenge for the biomedical application of nanoparticles

“…Specifically, addition of the biocorona has been evaluated for its role in altering the effectiveness of iron oxide nanoparticles as MRI contrast agents. Research has demonstrated that addition of the biocorona on superparamagnetic iron oxide nanoparticles does not significantly change T2 relaxation times; however, it can alter binding to cells [40, 41]. Further, the addition of the biocorona has been demonstrated to inhibit the targeting capabilities of transferrin-coated nanoparticles thus reducing their functionality [42].…”

PEGylated nanoparticles: protein corona and secondary structure

“…This method has been previously used to isolate the corona proteins from polystyrene, gold, semiconductor, and iron oxide nanoparticles. [13][14][15][16] For comparison, 20 µL of 0.5% FBS was added to 10 µL of Laemmli SDS buffer. All samples were heated for 5 min at 100 o C and loaded onto the gel for SDS-PAGE (130 V, 1 hr, 4-20% Mini-Protean TGX Stain-Free gels, Bio-Rad Laboratories Inc., Hercules, CA).…”

“…In the course of these applications, NPs are exposed to a complex environment of extracellular proteins. Previous work from our group, [11][12][13][14][15][16][17] and others, [18][19][20][21][22] has shown that proteins in solution, such as blood serum proteins, adsorb onto the surface of NPs forming a protein-NP complex. The protein corona ultimately dictates the interaction of the NP with the cell by determining the cellular receptors used by the protein-NP complex.…”

Isolation methods for particle protein corona complexes from protein-rich matrices

“…The same holds true for iron oxide nanoparticles that are used in high-sensitivity biomolecular magnetic resonance imaging (MRI) and tumor targeting. 31,[134][135][136][137][138] Additionally, iron oxide particles are also used for analytical purposes due to their magnetic properties. 139,140 As shown in Fig.…”