Ji Eun Bae

A Facile Synthesis, In vitro and In vivo MR Studies of d-Glucuronic Acid-Coated Ultrasmall Ln2O3 (Ln = Eu, Gd, Dy, Ho, and Er) Nanoparticles as a New Potential MRI Contrast Agent

A facile one-pot synthesis of d-glucuronic acid-coated ultrasmall Ln(2)O(3) (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles is presented. Their water proton relaxivities were studied to address their possibility as a new potential MRI contrast agent. We focused on the d-glucuronic acid-coated ultrasmall Dy(2)O(3) nanoparticle because it showed the highest r(2) relaxivity among studied nanoparticles. Its performance as a T(2) MRI contrast agent was for the first time proved in vivo through its 3 T T(2) MR images of a mouse, showing that it can be further exploited for the rational design of a new T(2) MRI contrast agent at high MR fields.

Water-Soluble MnO Nanocolloid for a Molecular T1 MR Imaging: A Facile One-Pot Synthesis, In vivo T1 MR Images, and Account for Relaxivities

A facile one-pot synthesis of a water-soluble MnO nanocolloid (i.e., D-glucuronic acid-coated MnO nanoparticle) is presented. The MnO nanoparticle in the MnO nanocolloid was coated with a biocompatible and hydrophilic D-glucuronic acid, and its particle diameter was nearly monodisperse and ranged from 2 to 3 nm. The average hydrodynamic diameter of the MnO nanocolloid was estimated to be 5 nm. The MnO nanoparticle was nearly paramagnetic down to T=3 K. The MnO nanocolloid showed a high longitudinal water proton relaxivity of r1=7.02 s(-1) mM(-1) with the r2/r1 ratio of 6.83 due to five unpaired S-state electrons of Mn(II) ion (S=5/2) as well as a high surface to volume ratio of the MnO nanoparticle. High contrast in vivo T1 MR images were obtained for various organs, showing the capability of the MnO nanocolloid as a sensitive T1 MRI contrast agent. The suggested three key-parameters which control the r1 and r2 relaxivities of nanocolloids (i.e., the S value of a metal ion, the spin structure, and the surface to volume ratio of a nanoparticle) successfully accounted for the observed r1 and r2 relaxivities of the MnO nanocolloid.

Potential dual imaging nanoparticle: Gd2O3 nanoparticle

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26–38 s−1mM−1 and r2/r1 = 1.4–1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

Paramagnetic dysprosium oxide nanoparticles and dysprosium hydroxide nanorods as T2 MRI contrast agents

We report here paramagnetic dysprosium nanomaterial-based T(2) MRI contrast agents. A large r(2) and a negligible r(1) is an ideal condition for T(2) MR imaging. At this condition, protons are strongly and nearly exclusively induced for T(2) MR imaging. The dysprosium nanomaterials fairly satisfy this because they are found to possess a decent r(2) but a negligible r(1) arising from L + S state 4f-electrons in Dy(III) ion ((6)H(15/2)). Their r(2) will also further increase with increasing applied field because of unsaturated magnetization at room temperature. Therefore, MR imaging and various physical properties of the synthesized d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles (d(avg) = 3.2 nm) and dysprosium hydroxide nanorods (20 × 300 nm) are investigated. These include hydrodynamic diameters, magnetic properties, MR relaxivities, cytotoxicities, and 3 tesla in vivo T(2) MR images. Here, MR imaging properties of dysprosium hydroxide nanorods have not been reported so far. These two samples show r(2)s of 65.04 and 181.57 s(-1)mM(-1), respectively, with negligible r(1)s at 1.5 tesla and at room temperature, no in vitro cytotoxicity up to 100 μM Dy, and clear negative contrast enhancements in 3 tesla in vivo T(2) MR images of a mouse liver, which will be even more improved at higher MR fields. Therefore, d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles with renal excretion can be a potential candidate as a sensitive T(2) MRI contrast agent at MR field greater than 3 tesla.

Mixed lanthanide oxide nanoparticles as dual imaging agent in biomedicine

There is no doubt that the molecular imaging is an extremely important technique in diagnosing diseases. Dual imaging is emerging as a step forward in molecular imaging technique because it can provide us with more information useful for diagnosing diseases than single imaging. Therefore, diverse dual imaging modalities should be developed. Molecular imaging generally relies on imaging agents. Mixed lanthanide oxide nanoparticles could be valuable materials for dual magnetic resonance imaging (MRI)-fluorescent imaging (FI) because they have both excellent and diverse magnetic and fluorescent properties useful for dual MRI-FI, depending on lanthanide ions used. Since they are mixed nanoparticles, they are compact, robust, and stable, which is extremely useful for biomedical applications. They can be also easily synthesized with facile composition control. In this study, we explored three systems of ultrasmall mixed lanthanide (Dy/Eu, Ho/Eu, and Ho/Tb) oxide nanoparticles to demonstrate their usefulness as dual T2 MRI–FI agents.

Synthesis of nanoparticle CT contrast agents: in vitro and in vivo studies

Abstract Water-soluble and biocompatible D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles were synthesized for the first time to be used as x-ray computed tomography (CT) contrast agents. Their average particle diameters were 3.2 ± 0.1 and 2.8 ± 0.1 nm for D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray attenuation. In vivo CT images were obtained after intravenous injection of an aqueous sample suspension of D-glucuronic acid coated Na2WO4 nanoparticles, and positive contrast enhancements in the kidney were clearly shown. These findings indicate that the nanoparticles reported in this study may be promising CT contrast agents.

Water-soluble D-glucuronic acid coated ultrasmall mixed Ln/Mn (Ln = Gd and Dy) oxide nanoparticles and their application to magnetic resonance imaging

Ultrasmall lanthanide oxide nanoparticles are promising materials as new magnetic resonance imaging (MRI) contrast agents because of their appreciable longitudinal (r1) or transverse (r2) water proton relaxivities at ultrasmall particle diameters. Two systems of d-glucuronic acid coated ultrasmall Ln/Mn (Ln = Gd and Dy) oxide nanoparticles with an average particle diameter of 2.0 nm were explored. The d-glucuronic acid coated ultrasmall Gd/Mn oxide nanoparticles showed strong positive contrast enhancements in 1.5 tesla T1 MR images while the d-glucuronic acid coated ultrasmall Dy/Mn oxide nanoparticles showed appreciable negative contrast enhancements in 1.5 tesla T2 MR images, proving their potential as T1 and T2 MRI contrast agents, respectively.