Surface Functionality Effect on the Relaxivity of Superparamagnetic Iron Oxide Nanoparticles as Negative MRI Contrast Agent

Nowadays, magnetic resonance imaging (MRI) thanks to its ability in providing non-invasive and three-dimensional examination of biological events is one of the most powerful diagnostic tolls in modern clinical medicine [1]. The MRI mechanism is based on the excitation and relaxation of hydrogen nuclei that are abundant in water and lipids of tissue. Differences in intrinsic longitudinal (T1) and transverse (T2) relaxation times of different parts of the tissues induce changes of MR signal intensity, which in turn result in imaging contrast [2]. However, it is often the case that the diseased and healthy tissues are similar in composition and MRI technology alone will not always differentiate the two. In these cases, a contrast agent is necessary to distinguish the normal and diseased tissue. Among different contrast agents, superparamagnetic iron oxide nanoparticles by enhancing the proton relaxation times in the tissue microenvironment are used as T2 (negative) contrast agents. However, because of aggregation of bare nanoparticles and quick sequesteration by RES system, a main challenge in using iron oxide nanoparticles as MRI contrast agent is their surface modification by a hydrophilic and biocompatible layer [3, 4]. In the present study, superparamagnetic iron oxide nanoparticles were synthesized in polyol media by monodisperse particle size distribution. Then the surface of nanoparticles was covalently modified with three different functionalities including amine, carboxylic acid, and PEG. The synthesized nanoparticles were characterized with different methods including FT-IR, TEM, PCS, and relaxometry. In order to investigate the effect of pH and surface charge on the relaxivity of nanoparticles, the r1 and r2 relaxivity of nanoparticles were examined in different pHs at 20 and 60MHz magnetic fields. The results showed that amine-functionalized nanoparticles agglomerate at basic or neutral media, while they are completely stable for a long time at acidic media because of induced charges on the surface of nanoparticles. Carboxylic-functionalized nanoparticles showed a reverse effect i.e. they agglomerate in acidic media, while they are stable at neutral or basic media. PEG-coated nanoparticles are completely stable in all studied basic or acidic media which can be attributed to the neutral and hydrophilic nature of PEG. Another main achievement is that by agglomeration and increasing the particle size, the r2/r1 ratio increases which is a main factor in evaluating the magnetic nanoparticles efficiency as T2 contrast agent.