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Composition-Tunable Ultrasmall Manganese Ferrite Nanoparticles: Insights into their In Vivo T 1 Contrast Efficacy
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Composition-Tunable Ultrasmall Manganese Ferrite Nanoparticles: Insights into their In Vivo T 1 Contrast Efficacy
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Journal Article
Composition-Tunable Ultrasmall Manganese Ferrite Nanoparticles: Insights into their In Vivo T 1 Contrast Efficacy
2019
Overview
The development of a highly efficient, low-toxicity, ultrasmall ferrite nanoparticle-based T
contrast agent for high-resolution magnetic resonance imaging (MRI) is highly desirable. However, the correlations between the chemical compositions,
T
relaxivities,
nano-bio interactions and toxicities remain unclear, which has been a challenge in optimizing the
T
contrast efficacy.
: Ultrasmall (3 nm) manganese ferrite nanoparticles (Mn
Fe
O
) with different doping concentrations of the manganese ions (x = 0.32, 0.37, 0.75, 1, 1.23 and 1.57) were used as a model system to investigate the composition-dependence of the
T
contrast efficacy. The efficacy of liver-specific contrast-enhanced MRI was assessed through systematic multiple factor analysis, which included the
T
relaxivity,
MRI contrast enhancement, pharmacokinetic profiles (blood half-life time, biodistribution) and biosafety evaluations (
cytotoxicity testing,
blood routine examination,
blood biochemistry testing and H&E staining to examine the liver).
: With increasing Mn doping, the T
relaxivities initially increased to their highest value of 10.35 mM
s
, which was obtained for Mn
Fe
O
, and then the values decreased to 7.64 m M
s
, which was obtained for the Mn
Fe
O
nanoparticles. Nearly linear increases in the
MRI signals (ΔSNR) and biodistributions (accumulation in the liver) of the Mn
Fe
O
nanoparticles were observed for increasing levels of Mn doping. However, both the
and
biosafety evaluations suggested that Mn
Fe
O
nanoparticles with high Mn-doping levels (x > 1) can induce significant toxicity.
: The systematic multiple factor assessment indicated that the Mn
Fe
O
(x = 0.75-1) nanoparticles were the optimal T
contrast agents with higher
efficacies for liver-specific MRI than those of the other compositions of the Mn
Fe
O
nanoparticles. Our work provides insight into the optimization of ultrasmall ferrite nanoparticle-based T
contrast agents by tuning their compositions and promotes the translation of these ultrasmall ferrite nanoparticles for clinical use of high-performance contrast-enhanced MRI.
Subject
/ Contrast Media - adverse effects
/ Contrast Media - pharmacokinetics
/ Contrast Media - pharmacology
/ Ferric Compounds - adverse effects
/ Ferric Compounds - chemistry
/ Ferric Compounds - pharmacokinetics
/ Ferric Compounds - pharmacology
/ Magnetic Resonance Imaging - methods
/ Manganese Compounds - adverse effects
/ Manganese Compounds - chemistry
/ Manganese Compounds - pharmacokinetics
/ Manganese Compounds - pharmacology
/ Nanoparticles - administration & dosage
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