Magnetic resonance imaging (MRI) contrast agents represent one of the major applications for magnetic nanoparticles. Theoretically, the particle size, state of aggregation, and surface modification have strong impacts on the relaxivity of magnetic iron oxide nanoparticles. The former two effects have received investigations both theoretically and experimentally. While the impacts of surface coating structure on the magnetic relaxivity of iron oxide nanoparticles are awaiting further studies for deep understanding of their overall contrast enhancement effects.
    To disclose the effects of the anchoring group of surface ligands on the relaxometric properties of Fe₃O₄ nanoparticles, three different types of PEG2000 molecules bearing anchoring groups such as diphosphate, hydroxamate, and catechol, were designed and used to replace the hydrophobic oleate ligands of 3.6 nm and 10.9 nm Fe₃O₄ nanoparticles. The high binding affinity of these anchoring groups for Fe3+ enables reliable ligand exchange process for achieving PEGylated Fe₃O₄ particles well dispersible in water. Dynamic light scattering studies were carried out for excluding the influence of particle aggregation on the relaxometric behavior of the PEGylated particles. Then, the contrast enhancement properties of the resultant nanoparticles were carefully compared and the related theories were simplified to facilitate the discussion on the impacts of the anchoring group on transverse relaxivity (r2), longitudinal relaxivity (r1), and r2/r1 ratio. It was found out that the saturated magnetization of the Fe₃O₄ particles, independent of particle size, were closely related to the binding affinity of the anchoring group, so did r2. In addition, r2 and r2/r1 ratio were strongly correlated with the presence of p-p or p-p conjugation structure in the anchoring groups of the PEG ligands. Moreover, in literature, great efforts have been spent to decrease the r2/r1 ratio down to at least 6 in order to enable small iron oxide particles as T1 contrast agent. Nevertheless, the current investigation shows that 3.6 nm Fe₃O₄ particles coated by hydroxamate-PEG and catechol-PEG present obvious T1 contrast effect even though their r2/r1 ratios higher than 11, indicating the r2/r1 ratio as the commonly used criterion for judging the suitability of iron oxide particles as T1 contrast agent may need to be reconsidered. The relative results have been accepted by Advanced Materials.
    The current investigations for the first time, in combination with theories, disclose that the impacts of anchoring group of organic ligands on the relaxometric behaviors of the underlying magnetic iron oxide nanocrystals and thus provide a new strategy for tailoring the magnetic nanoparticles for versatile MR imaging applications.
                                                                                                                                                                                                          Jianfeng Zeng et al.