Superparamagnetic iron oxide nanoparticles (SPIONs) are
recognized
as one of the most beneficial tools for biomedicine, especially in
theranostic applications. Even though SPIONs have excellent properties
regarding their biocompatibility and unique magnetic properties, they
lack stability in biological fluids. To stabilize and increase the
specificity of the SPIONs to target desirable cells or tissues, several
surface coatings have been introduced. These surface coatings can
lead to different preferences of serum protein bindings, which ultimately
determine their behaviors in vitro and in
vivo. Thus, understanding the interaction of SPIONs with
biological systems is important for their biocompatible design and
clinical applications. In this study, using proteomic analyses, we
analyzed the protein corona fingerprints on SPIONs with two different
coatings, including citrate and riboflavin, that have been widely
used as surface coatings and ligands for enhancing cellular uptake
in breast cancer cells. Though both citrate-coated SPIONs (C-SPIONs)
and riboflavin-coated SPIONs (Rf-SPIONs) showed similar sizes and
zeta potentials, we found that Rf-SPIONs adsorbed more serum proteins
than bare SPIONs (B-SPIONs) or C-SPIONs, which was likely due to the
higher hydrophobicity of the riboflavin. The enriched proteins consisted
mainly of immune-responsive and blood coagulation proteins with different
fingerprint profiles. Cellular uptake studies in MCF-7 breast cancer
cells comparing the activities of preformed and in situ coronas showed different uptake behaviors, suggesting the role of
protein corona formation in promoting the interaction between the
SPIONs and the cells. The results obtained here provide the essential
information for further development of the potential strategy to reduce
or stimulate immune response in vivo to increase
therapeutic applications of both C-SPIONs and Rf-SPIONs.