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Yongmin Chang - One of the best experts on this subject based on the ideXlab platform.
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Dextran‐Coated Ultrasmall Gd2O3 Nanoparticles as Potential T1 MRI Contrast Agent
ChemistrySelect, 2016Co-Authors: Wenlong Xu, Xu Miao, In-taek Oh, Kwon Seok Chae, Yongmin ChangAbstract:Ultrasmall gadolinium oxide (Gd2O3) nanoparticles coated with dextran (M‾ r=1500 amu) were prepared through one-pot synthesis and their potential to act as a T1 MRI Contrast Agent was investigated. The dextran-coated ultrasmall Gd2O3 nanoparticles were highly water-dispersible, with an average particle diameter of 1.5 nm and an average hydrodynamic diameter of 12.4 nm, and non-toxic, as determined in a cellular cytotoxicity test. The longitudinal (r1) and transverse (r2) water proton relaxivities were estimated to be 12.2 and 29.3 s−1mM−1 (r2/r1=2.4), respectively, larger than those of commercial Gd-chelates. This r1 value is also greater than those for previously reported dextran-coated large Gd2O3 nanoparticles with particle diameter bigger than 20 nm. Positive Contrast magnetic resonance (MR) images were obtained after intravenous injection of a sample solution into a mouse tail, demonstrating the potential of dextran-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI Contrast Agent.
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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
ACS Applied Materials & Interfaces, 2011Co-Authors: Krishna Kattel, Badrul Alam Bony, Jong Su Baeck, Eun Jung Lee, Woo Choul Heo, Ja Young Park, Han Gyeol Kim, Jae-jun Lee, Seong-uk Jin, Yongmin ChangAbstract:A facile one-pot synthesis of d-glucuronic acid-coated ultrasmall Ln2O3 (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 Dy2O3 nanoparticle because it showed the highest r2 relaxivity among studied nanoparticles. Its performance as a T2 MRI Contrast Agent was for the first time proved in vivo through its 3 T T2 MR images of a mouse, showing that it can be further exploited for the rational design of a new T2 MRI Contrast Agent at high MR fields.
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paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced t1 MRI Contrast Agent account for large longitudinal relaxivity optimal particle diameter and in vivo t1 mr images
ACS Nano, 2009Co-Authors: Ja Young Park, Jaechang Jung, Kwon Seok Chae, Myung Ju Baek, Eun Sook Choi, Yongmin ChangAbstract:Paramagnetic ultrasmall gadolinium oxide (Gd2O3) nanoparticles with particle diameters (d) of ∼1 nm were synthesized by using three kinds of Gd(III) ion precursors and by refluxing each of them in tripropylene glycol under an O2 flow. A large longitudinal relaxivity (r1) of water proton of 9.9 s−1 mM−1 was estimated. As a result, high Contrast in vivo T1 MR images of the brain tumor of a rat were observed. This large r1 is discussed in terms of the huge surface to volume ratio (S/V) of the ultrasmall gadolinium oxide nanoparticles coupled with the cooperative induction of surface Gd(III) ions for the longitudinal relaxation of a water proton. It is found from the d dependence of r1 that the optimal range of d for the maximal r1, which may be used as an advanced T1 MRI Contrast Agent, is 1−2.5 nm.
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gold nanoparticles functionalised by gd complex of dtpa bis amide conjugate of glutathione as an MRI Contrast Agent
Bioorganic & Medicinal Chemistry Letters, 2008Co-Authors: Jiae Park, Yongmin Chang, Heekyung Kim, Pattubala A N Reddy, Insung Kim, Gabchul Kim, Taejeong KimAbstract:Abstract The work is directed toward the synthesis of gold nanoparticles (Au NPs) coated with paramagnetic Gd-complex of DTPA-bis(amide) conjugate of glutathione (GdL) for use as a highly efficient MRI Contrast Agent. Well-dispersed spherical Au NPs coated with gadolinium complexes, abbreviated as Au@GdL, have been obtained; the mean size of Au@GdL is 5–7 nm, and the numbers of GdL are 1.36 × 104 per Au NP. Au@GdL exhibits high longitudinal (r1) and transverse (r2) relaxivities of 1.87 × 105 and 3.02 × 105 mM−1 s−1, respectively.
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Nanoparticles of magnetic ferric oxides encapsulated with poly(D,L latide-co-glycolide) and their applications to magnetic resonance imaging Contrast Agent
Journal of Magnetism and Magnetic Materials, 2004Co-Authors: Jong-ryul Jeong, Young-hwan Chang, Sung-chul Shin, Yongmin ChangAbstract:Abstract Magnetic nanoparticles of Fe 3 O 4 encapsulated with Poly(D,L lactide-co-glycolide) (PLGA) were prepared for magnetic resonance imaging (MRI) Contrast Agent by using an emulsification–diffusion method. In this study, we have investigated the effects of homogenizer and agitator speed on the nanoparticles formation and the magnetic properties of ferrofluid nanoparticles encapsulated with PLGA with varying the ferromagnetic particle size from 10 to 180 nm. We have confirmed that the ferrofluid nanoparticles encapsulated with PLGA could be utilized as an MRI Contrast Agent from experiments in animal tissue.
Robert N Muller - One of the best experts on this subject based on the ideXlab platform.
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polyglycerol grafted superparamagnetic iron oxide nanoparticles highly efficient MRI Contrast Agent for liver and kidney imaging and potential scaffold for cellular and molecular imaging
Contrast Media & Molecular Imaging, 2012Co-Authors: Nasser Arsalani, Hassan Fattahi, Sophie Laurent, Carmen Burtea, Luce Vander Elst, Robert N MullerAbstract:Polyglycerol as a water-soluble and biocompatible hyperbranched polymer was covalently grafted on the surface of superparamagnetic iron oxide nanoparticles. With this aim, superparamagnetic magnetite nanoparticles were prepared by coprecipitation in aqueous media, then the surface of nanoparticles was modified to introduce the reactive groups on the surface of nanoparticles. After that, polyglycerol was grafted on the surface of nanoparticles by ring-opening anionic polymerization of glycidol using n-bulyllithium as initiator. The magnetometry, relaxometry and phantom MRI experiments of this highly stable ferrofluid showed its high potential as a negative MRI Contrast Agent. Calculated r1 and r2 relaxivities at different magnetic fields were higher than the values reported for commercially available iron oxide Contrast Agents. The in vivo MRI studies showed that, after intravenous injection into mice, the particles produced a strong negative Contrast in liver and kidneys, which persisted for 80 min (in liver) to 110 min (in kidneys). The negative Contrast of the liver and kidneys weakened over the time, suggesting that polyglycerol coating renders the nanoparticles stealth and possibly optimal for renal excretion. Copyright © 2012 John Wiley & Sons, Ltd.
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synthesis and physicochemical characterization of gd c4 thyroxin dtpa a potential MRI Contrast Agent evaluation of its affinity for human serum albumin by proton relaxometry nmr diffusometry and electrospray mass spectrometry
Journal of Physical Chemistry B, 2010Co-Authors: Celine Henoumont, Sophie Laurent, Vander L Elst, Robert N MullerAbstract:Gd-C(4)-thyroxin-DTPA, a potential MRI Contrast Agent, was synthesized from Gd-DTPA and thyroxine, which interacts strongly with human serum albumin (HSA). It was characterized in water by its relaxometric properties and its stability versus zinc transmetalation. The affinity of the complex for HSA was studied by using three different methods: proton relaxometry, NMR diffusometry, and electrospray mass spectrometry. From the results, it appears that Gd-C(4)-thyroxin-DTPA exhibits a relatively high relaxivity (r(1) = 9.01 s(-1) mM(-1) at 1.5 T and 310 K), a good stability versus zinc transmetalation, and a strong interaction with HSA (K(a) approximately 10,000 M(-1) with two binding sites). The kinetics of the exchange between the bound and the free form of the complex was evaluated by the NMR diffusometry technique. Competition experiments have allowed the assignment of the chelate's binding site on HSA.
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specific e selectin targeting with a superparamagnetic MRI Contrast Agent
Contrast Media & Molecular Imaging, 2006Co-Authors: Sebastien Boutry, Sophie Laurent, Luce Vander Elst, Robert N MullerAbstract:Abstract Targeting of the endothelial inflammatory adhesion molecule E-selectin by magnetic resonance imaging (MRI) was performed with a superparamagnetic Contrast Agent in the context of in vitro and in vivo models of inflammation. The specific Contrast Agent was obtained by grafting a synthetic mimetic of sialyl Lewis(x) (sLe(x)), a natural ligand of E-selectin expressed on leukocytes, on the dextran coating of ultrasmall particles of iron oxide (USPIO). This new Contrast Agent, called USPIO-g-sLe(x), was tested, in vitro, on cultured human umbilical vein endothelial cells (HUVECs) stimulated to express inflammatory adhesion molecules, and in vivo, on a mouse model of hepatitis. In vitro, HUVECs were stimulated with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and were then incubated with USPIO-g-sLe(x) or ungrafted USPIO. In vivo, hepatitis was induced on NMRI mice by injection of concanavalin A (Con A). USPIO-g-sLe(x) and ungrafted USPIO were injected intravenously. In vitro results showed an extensive retention of USPIO-g-sLe(x) on TNF-alpha stimulated HUVECs. Image intensity and R(2) measurements performed on T(2)-weighted MR images demonstrated a significantly higher binding of USPIO-g-sLe(x) on stimulated HUVECs. In vivo, USPIO are known to pass through the fenestrae of the liver and to be captured by Kupffer cells, inducing a loss of signal intensity on T(2)-weighted MR images. Unexpectedly, when injected to Con A-treated mice, USPIO-g-sLe(x) induced a significantly lower attenuation of liver signal intensity than USPIO or USPIO-g-sLe(x) injected to healthy mice, or USPIO injected to Con A-treated mice, suggesting that the specific Contrast media is retained extracellularly by an interaction with E-selectin overexpressed on the vascular endothelium. Both in vitro and in vivo results therefore indicate that USPIO-g-sLe(x) is recognizing endothelial E-selectin. USPIO-g-sLe(x) is thus well suited for the MRI diagnosis of inflammation and for the in vitro evaluation of endothelial cells activation.
Thomas J Meade - One of the best experts on this subject based on the ideXlab platform.
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the synthesis and in vitro testing of a zinc activated MRI Contrast Agent
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Jody L Major, Giacomo Parigi, Claudio Luchinat, Thomas J MeadeAbstract:Zinc(II) plays a vital role in normal cellular function as an essential component of numerous enzymes, transcription factors, and synaptic vesicles. While zinc can be linked to a variety of physiological processes, the mechanisms of its cellular actions are less discernible. Here, we have synthesized and tested a Zn(II)-activated magnetic resonance imaging (MRI) Contrast Agent in which the coordination geometry of the complex rearranges upon binding of Zn(II). In the absence of Zn(II) water is restricted from binding to a chelated Gd(III) ion by coordinating acetate arms resulting in a low relaxivity of 2.33 mM−1·s−1 at 60 MHz. Upon addition of Zn(II) the relaxivity of the Gd(III)–Zn(II) complex increases to 5.07 mM−1·s−1 and is consistent with one water molecule bound to Gd(III). These results were confirmed by nuclear magnetic relaxation dispersion analysis. There was no observed change in relaxivity of the Gd(III) complex when physiologically competing cations Ca(II) and Mg(II) were added. A competitive binding assay gave a dissociation constant of 2.38 × 10−4 M for the Gd(III)–Zn(II) complex. In vitro magnetic resonance images confirm that Zn(II) concentrations as low as 100 μM can be detected by using this Contrast Agent.
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synthesis and visualization of a membrane permeable MRI Contrast Agent
Journal of Biological Inorganic Chemistry, 2003Co-Authors: Matthew J Allen, Thomas J MeadeAbstract:The study of in vivo developmental events has undergone significant advances with the advent of biological molecular imaging techniques such as computer enhanced light microscopy imaging, positron emission tomography (PET), micro-CT, and magnetic resonance imaging (MRI). MRI has proven to be a particularly powerful tool in clinical and biological settings. Images can be acquired of opaque living animals, with the benefit of tracking events of extended periods of time on the same specimen. Contrast Agents are routinely used to enhance regions, tissues, and cells that are magnetically similar but histologically distinct. A principal barrier to the development of MR Contrast Agents for investigating developmental biological questions is the ability to deliver the Agent across cellular membranes. As part of our research, we are investigating a number of small molecules that facilitate transport of charged and uncharged species across cell membranes. Here we describe the synthesis and testing of a Gd(III)-based MR Contrast Agent conjugated to polyarginine that is able to permeate cell membranes. We confirmed cellular uptake of the Agent using two-photon laser microscopy to visualize a Eu(III) derivative of the Contrast Agent in cell culture, and verified this uptake by T1 analysis of the Gd(III) Agent in cells.
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mechanistic studies of a calcium dependent MRI Contrast Agent
Inorganic Chemistry, 2002Co-Authors: Giacomo Parigi, Marco Fragai, Claudio Luchinat, Thomas J MeadeAbstract:Intracellular Ca^(2+) plays an important role in signal transduction, and we are developing new MRI techniques to study its regulation in living animals. We have reported on an MRI Contrast Agent (DOPTA-Gd) where the relaxivity of the complex is controlled by the presence or absence of the divalent ion Ca^(2+). By structurally modulating inner-sphere access of water to a chelated Gd^(3+) ion, we observe a substantial and reversible change in T_1 upon the addition of Ca^(2+) and not other divalent ions. Luminescence lifetime and NMRD measurements of the complex have been acquired, and several parameters contribute to the Ca^(2+) dependent relaxivity change of DOPTA-Gd. The number of inner-sphere water molecules is more than doubled after the Ca^(2+) concentration is increased. This finding strongly supports the proposed conformational change of DOPTA-Gd when Ca^(2+) is bound. Relaxometric measurements confirm these results and provide an indication that second-sphere water molecules are probably responsible for paramagnetic relaxation enhancement in the absence of Ca^(2+). After Ca^(2+) is bound to DOPTA-Gd, the molecule undergoes a substantial conformational change that opens up the hydrophilic face of the tetraazacyclododecane macrocycle. This change dramatically increases the accessibility of chelated Gd^(3+) ion to bulk solvent. The design of this class of calcium-activated MR Contrast Agent was based primarily on the assumption that the number of coordinated inner-sphere water molecules would be the dominating factor in observed relaxivity measurements. This result has been confirmed; however, careful mechanistic studies reveal that additional factors are involved in this process.
Alan Jasanoff - One of the best experts on this subject based on the ideXlab platform.
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sensing intracellular calcium ions using a manganese based MRI Contrast Agent
Nature Communications, 2019Co-Authors: Ali Barandov, Benjamin B Bartelle, Catherine G Williamson, Emily S Loucks, Stephen J Lippard, Alan JasanoffAbstract:Calcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic Contrast Agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI Contrast when stimulated with pharmacological Agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI.
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sensing intracellular calcium ions using a manganese based MRI Contrast Agent
Nature Communications, 2019Co-Authors: Ali Barandov, Benjamin B Bartelle, Catherine G Williamson, Emily S Loucks, Stephen J Lippard, Alan JasanoffAbstract:Calcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic Contrast Agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI Contrast when stimulated with pharmacological Agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI. There are only few MRI-compatible calcium reporters and they are limited to measuring extracellular calcium levels. Here the authors develop and validate a cell-permeable, manganese-based paramagnetic MRI Contrast Agent that enables monitoring intracellular calcium signals in vivo in the rat brain.
Laurence Motte - One of the best experts on this subject based on the ideXlab platform.
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Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic
Journal of Osteoporosis, 2010Co-Authors: Yoann Lalatonne, Maelle Monteil, H. Jouni, Jean-michel Serfaty, Odile Sainte-catherine, Nicole Lièvre, S. Kusmia, Pierre Weinmann, Marc Lecouvey, Laurence MotteAbstract:A bone targeting nanosystem is reported here which combined magnetic Contrast Agent for Magnetic Resonance Imaging (MRI) and a therapeutic Agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI Contrast Agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI Contrast Agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show that @di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.
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Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic
Journal of Osteoporosis, 2010Co-Authors: Yoann Lalatonne, Maelle Monteil, H. Jouni, Jean-michel Serfaty, Odile Sainte-catherine, Nicole Lièvre, S. Kusmia, Pierre Weinmann, Marc Lecouvey, Laurence MotteAbstract:A bone targeting nanosystem is reported here which combined magnetic Contrast Agent for Magnetic Resonance Imaging (MRI) and a therapeutic Agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic gamma(Fe2O3) nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI Contrast Agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2* Contrast Agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show that gamma(Fe2O3) @di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.