Manganese‐enhanced MRI of rat brain based on slow cerebral delivery of manganese(II) with silica‐encapsulated Mn_xFe_1–xO nanoparticles

Abstract

In this work, we report a monodisperse bifunctional nanoparticle system, MIO@SiO2 -RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. In vivo MRI of rats injected intravenously with MIO@SiO2-RITC nanoparticles exhibited enhancement of the T1 contrast in brain tissue, in particular a time-delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of MIO@SiO2-RITC nanoparticles in the liver, resulting in the slow release of manganese(II) [Mn(II)] into the blood pool and, subsequently, accumulation in the brain tissue. Thus, T1-weighted contrast enhancement was clearly detected in the anatomic structure of the brain as time progressed. In addition, T2*-weighted images of the liver showed a gradual darkening effect. Here, we demonstrate the concept of the slow release of Mn(II) for neuroimaging. This new nanoparticle-based manganese contrast agent allows one simple intravenous injection (rather than multiple infusions) of Mn(II) precursor, and results in delineation of the detailed anatomic neuroarchitecture in MRI; hence, this provides the advantage of the long-term study of neural function.

Synthesis of Ferromagnetic Fe0.6Mn0.4O Nanoflowers as a New Class of Magnetic Theranostic Platform for In Vivo T1‐T2 Dual‐Mode Magnetic Resonance Imaging and Magnetic Hyperthermia Therapy

“…These manipulations of nanoparticles would inevitably lead to a poor specific absorption rate (SAR), hampering their application in magnetic hyperthermia treatment. Recently, a new wüstite iron‐manganese oxide (Fe 1− x Mn x O, IMO) nanoparticle has attracted intensive interest because of its rich morphology and diverse magnetism . The extraordinary stability of the IMO alloy nanoparticle compared to single‐phase FeO and MnO due to Hume‐Rothery rules, makes it a good candidate as a novel magnetic nanoagent for biomedical applications .…”

Targeting T₁ and T₂ dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles

“…Regarding the ion leaching, in contrast to MnCl 2 solution, Mn ions leaching from Mn-based NPs have been demonstrated to be slower and Mn-based NPs showed no significant toxic effects on cells at a very high dosage of 200 µg/mL in some previous studies. 30,31 Actually, to avoid high cytotoxicity of Mn, some researchers employed Mn-based NPs as a sustained release delivery of Mn ions for neuroimaging instead of MnCl 2 solution. 30,31 Because of clearance and degradation of NPs from the labeled cells, it was reasonable that the signal intensity from P 1 to P 4 in T 2 -weighted MR images gradually increased.…”

“…30,31 Actually, to avoid high cytotoxicity of Mn, some researchers employed Mn-based NPs as a sustained release delivery of Mn ions for neuroimaging instead of MnCl 2 solution. 30,31 Because of clearance and degradation of NPs from the labeled cells, it was reasonable that the signal intensity from P 1 to P 4 in T 2 -weighted MR images gradually increased. However, it was very interesting that the signal intensity of these cells firstly increased and then decreased in T 1 -weighted MR images.…”

“…Divalent manganese ions have five unpaired electrons and are paramagnetic, which have been regarded as strong T 1 MRI CAs. 31 Additionally, the reduction of NP size accompanied with the degradation of MnFe 2 O 4 may also contribute to the high signal intensity of P 3 in T 1 -weighted MR images. It is known that the surface atom ratio is inversely proportional to the particle size and large particles exhibit lower surface Mn 2+ ratio, leading to a small longitudinal relaxivity.…”

“…The above two effects can significantly shorten the T 1 relaxation time of the surrounding protons and induce hyperintensity in T 1 -weighted imaging. 19,[28][29][30][31] 30,32 to improve the accuracy of diagnosis of MRI greatly.…”