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.
Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM(-1) s(-1) with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.
The shape of magnetic nanoparticles is of great importance in determining their contrast abilities for magnetic resonance imaging. Various magnetic nanoparticles have been developed to achieve high T or T relaxivities, but the mechanism on how morphology influences the water proton relaxation process is still unrevealed. Herein we synthesize manganese-doped iron oxide (MnIO) nanoparticles of the same volume with six different shapes and reveal the relationship between morphologies and T/ T relaxation rates. The morphology of magnetic nanoparticles largely determines the effective radius and the gradient of stray field, which in turn affects the transverse relaxation rate. The longitudinal relaxivity has positive correlation with the surface-area-to-volume ratio and the occupancy rate of effective metal ions on exposed surfaces of magnetic nanoparticles. These findings together with the summary of r/ r ratios could help to guide the screening for the optimal shapes of promising T or T contrast agents. Varying effective radii could be utilized to change negative contrast abilities. The surface-area-to-volume ratio and the amount of effective metal ions on exposed surface are instrumental for tuning positive contrast abilities. These principles could serve as guidelines for design and development of high-performance nanoparticle-based contrast agents.
Cation exchange is a powerful means to adjust the properties of nanocrystals through composition change with morphology retention. Herein, we demonstrate that cation exchange can engineer the composition of iron oxide nanocrystals to dramatically improve their contrast ability in magnetic resonance imaging (MRI). We successfully construct manganese and zinc engineered iron oxide nanoparticles with diverse shapes (sphere, cube, and octapod) by facile cation exchange reactions. Extended X-ray absorption fine structure (EXAFS) study indicates that Mn2+ and Zn2+ ions are doped into the crystal lattice of ferrite, and more importantly, most of them are distributed in T d sites of ferrite. These engineered shaped-anisotropic iron oxide nanoparticles exhibit both high saturated magnetization and large effective boundary radii, which leads to remarkable transverse relaxivity (r 2), for example, 754.2 mM–1 s–1 for zinc engineered octapod iron oxide nanoparticles. These engineered iron oxide nanoparticles, as high-performance T 2 contrast agents for in vivo MR imaging, enable sensitive imaging of early hepatic tumors and metastatic hepatic tumors (as small as 0.4 mm), holding great promise for prompt and accurate diagnosis of cancers and metastases.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.