Magnetic nanoparticles (NPs) are increasingly being considered for use in biomedical applications such as biosensors, imaging contrast agents and drug delivery vehicles. In a biological fluid, proteins associate in a preferential manner with NPs. The small sizes and high curvature angles of NPs influence the types and amounts of proteins present on their surfaces. This differential display of proteins bound to the surface of NPs can influence the tissue distribution, cellular uptake and biological effects of NPs. To date, the effects of adsorption of a protein corona (PC) on the magnetic properties of NPs have not been considered, despite the fact that some of their potential applications require their use in human blood.Here, to investigate the effects of a PC (using fetal bovine serum) on the MRI contrast efficiency of superparamagnetic iron oxide NPs (SPIONs), we have synthesized two series of SPIONs with variation in the thickness and functional groups (i.e. surface charges) of the dextran surface coating. We have observed that different physico-chemical characteristics of the dextran coatings on the SPIONs lead to the formation of PCs of different compositions. 1 H relaxometry was used to obtain the longitudinal, r 1 , and transverse, r 2 , relaxivities of the SPIONs without and with a PC, as a function of the Larmor frequency. The transverse relaxivity, which determines the efficiency of negative contrast agents (CAs), is very much dependent on the functional group and the surface charge of the SPIONs' coating. The presence of the PC did not alter the relaxivity of plain SPIONs, while it slightly increased the relaxivity of the negatively charged SPIONs and dramatically decreased the relaxivity of the positively charged ones, which was coupled with particle agglomeration in the presence of the proteins. To confirm the effect of the PC on the MRI contrast efficiency, in vitro MRI experiments at n ¼ 8.5 MHz were performed using a low-field MRI scanner. The MRI contrasts, produced by different samples, were fully in agreement with the relaxometry findings.It is well-recognized that the surface of nanoparticles (NPs) is covered by biomolecules (proteins, sugars and lipids) upon coming into contact with biological systems, resulting in the formation of a protein "corona" that is strongly associated with the NPs' surface and that denes how living organisms (e.g. cells) "see" the NPs in a biological milieu. 1-5 According to previous reports, the cell "sees" a nano-system in which the NPs are covered by a "hard" corona of slowly exchanging proteins with a surrounding "so" corona consisting of weakly interacting and rapidly exchanging proteins. 6 The composition of the protein corona (PC) is highly dependent on the physicochemical properties of the NPs such as their size, composition, and surface characteristics. 7 Superparamagnetic iron oxide nanoparticles (SPIONs) have been recognized as very promising nanosystems with good biocompatibility 8,9 and high potential to be used for diagnosis and therapy simultaneou...