Magnetic nanoparticles (MNPs) have been extensively explored as magnetic resonance imaging (MRI) contrast agents. With the increasing complexity in the structure of modern MNPs, the classical Solomon-Bloembergen-Morgan and the outer-sphere quantum mechanical theories established on simplistic models have encountered limitations for defining the emergent phenomena of relaxation enhancement in MRI. We reviewed recent progress in probing MRI relaxivity of MNPs based on structural features at the molecular and atomic scales, namely the structure-relaxivity relationships, including size, shape, crystal structure, surface modification, and assembled structure. We placed a special emphasis on bridging the gaps between classical simplistic models and modern MNPs with elegant structural complexity. In the pursuit of novel MRI contrast agents, we hope this review will spur the critical thinking for design and engineering of novel MNPs for MRI applications across a broad spectrum of research fields.

We report the design and synthesis of small-sized zwitterion-coated gadolinium-embedded iron oxide (GdIO) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects. The combination of spin-canting effects and the collection of gadolinium species within small-sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect. For example, GdIO nanoparticles with a diameter of ~4.8 nm exhibited a high r1 relaxivity of 7.85 mM−1 · S−1 and a low r2/r1 ratio of 5.24. After being coated with zwitterionic dopamine sulfonate molecules, the 4.8 nm GdIO nanoparticles showed a steady hydrodynamic diameter (~5.2 nm) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption. This study provides a valuable strategy for the design of highly sensitive iron-oxide-based T1 contrast agents with relatively long circulation half-lives (~50 min), efficient tumor passive targeting (SKOV3, human ovarian cancer xenograft tumor as a model), and the possibility of rapid renal clearance after tumor imaging.

In this paper, we demonstrate the tunable T1 and T2 contrast abilities of engineered iron oxide nanoparticles with high performance for liver contrast-enhanced magnetic resonance imaging (MRI) in mice. To enhance the diagnostic accuracy of MRI, large numbers of contrast agents with T1 or T2 contrast ability have been widely explored. The comprehensive investigation of high-performance MRI contrast agents with controllable T1 and T2 contrast abilities is of high importance in the field of molecular imaging. In this study, we synthesized uniform manganese-doped iron oxide (MnIO) nanoparticles with controllable size from 5 to 12 nm and comprehensively investigated their MRI contrast abilities. We revealed that the MRI contrast effects of MnIO nanoparticles are highly size-dependent. By controlling the size of MnIO nanoparticles, we can achieve T1-dominated, T2-dominated, and T1-T2 dual-mode MRI contrast agents with much higher contrast enhancement than the corresponding conventional iron oxide nanoparticles.

This review is a systematic description of shape-dependent effects on nanomaterials from theory, synthesis, property to application, meanwhile, elaborates and predicts the properties and applications of nanoparticles with diverse morphologies in physicochemical and biomedical fields.

Manganese-doped magnetite nanoparticles as magnetic resonance imaging (MRI) contrast agents have been well developed in recent years due to their higher saturation magnetization and stronger transverse (T 2 ) contrast ability compared to parent magnetite. However, the underlying role that manganese doping plays in altering the contrast ability of magnetite is still not thoroughly understood. Herein, we investigate the effects of manganese doping on changes of ferrite crystal structures, magnetic properties, and contrast abilities. We developed a successful one-pot synthesis of uniform manganese-doped magnetite (Mn x Fe 3−x O 4 ) nanoparticles with different manganese contents (x = 0−1.06). The saturation magnetization and T 2 contrast ability of ferrite nanoparticles increase along with rising manganese proportion, peak when the doping level of Mn x Fe 3−x O 4 reaches x = 0.43, and decrease dramatically as the manganese percentage continues to augment. At high manganese doping level, the manganese ferrite nanoparticles may undergo lattice distortion according to analysis of XRD patterns and lattice distances, which may result in low saturation magnetization and eventually low T 2 contrast ability. The Mn x Fe 3−x O 4 nanoparticles (x = 0.43) with a diameter of ∼18.5 nm exhibit the highest T 2 relaxivity of 904.4 mM −1 s −1 at 7.0 T among all the samples and show a much stronger T 2 contrast effect for liver imaging than that of other iron oxide contrast agents. These results indicate that the optimized T 2 contrast ability of manganese ferrite nanoparticles could be achieved by tuning the manganese doping level. This work also opens a new field of vision for developing high-performance T 2 contrast agents by modulating the metal composition of nanoparticles.