Browsing by Author "Singh, Gyan"

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A switch-on MRI contrast agent for noninvasive visualization of methylmercury
(2015-01-01)
Singh, Gyan
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Hsu, Kuang-Mei
;
Chen, Yu-Jen
;
Wu, Shou-Cheng
;
Chen, Chiao-Yun
This communication presents the first Gd(III)-based T-1 MRI contrast agent, o-MeHgGad, for noninvasive visualization of CH3Hg+. o-MeHgGad showed a relaxivity enhancement of 62% in the presence of 1 equiv. of CH3Hg+. Moreover, a noticeable contrast enhancement was recorded in the liver, kidney, and intestine of mice exposed to CH3Hg+. Thus, the newly designed contrast agent has the potential to be used for in vivo bio-imaging of CH3Hg+ and could be useful for biomedical applications.
Development of a Gd(III)-Based Receptor-Induced Magnetization Enhancement (RIME) Contrast Agent for beta-Glucuronidase Activity Profiling
(2012-11-19)
Chen, Shih-Hsien
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Kuo, Yu-Ting
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Singh, Gyan
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Cheng, Tian-Lu
;
Su, Yu-Zheng
beta-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor induced magnetization enhancement (pro RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FP beta Gu)]) for molecular imaging of beta-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a beta-glucuronidase substrate (beta-D-glucopyranuronic acid). The binding association constant (K-A) of [Gd(DOTA-FP beta Gu)] is 7.42 X 10(2), which is significantly lower than that of a commercially available MS-325 (K-A = 3.0 x 10(4)) RIME contrast agent. The low K-A value of [Gd(DOTA-FP beta Gu)] is due to the pendant beta-D-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FP beta Gu)] can be used for detection of beta-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FP beta Gu)] was elucidated by LC-MS. The kinetics of beta-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FP beta Gu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with K-m = 1.38 mM, K-cat = 3.76 x 10(3), and k(cat)/K-m = 2.72 x 10(3) M-1 s(-1). The low K-m value indicates high affinity of beta-glucuronidase for [Gd(DOTA-FP beta Gu)] FP beta Gu) at physiological pH. Relaxometric studies revealed that T-1 relaxivity of [Gd(DOTA-FP beta Gu)] changes in response to the concentration of beta-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FP beta Gu)] showed significant change in MR image signal in the presence of beta-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of beta-glucuronidase. [GRAPHICS] .
Direct Synthesis of Vertically Interconnected 3-D Graphitic Nanosheets on Hemispherical Carbon Particles by Microwave Plasma CVD
(2011-03-01)
Tiwari, Jitendra N.
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Tiwari, Rajanish N.
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Singh, Gyan
;
Lin, Kun-Lin
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材料科學與工程學系
High-quality, free-standing, and vertically interconnected three-dimensional (3-D) graphitic nanosheets (GNSs) were synthesized over the surface of hemispherical carbon particles/GaN at 700 A degrees C by microwave plasma chemical vapor deposition (CVD) in presence of methane gas, whereas the hemispherical carbon particles have been directly deposited on GaN/sapphire template. The GNSs are similar to 1-5 nm in thickness and have a graphitic flake structure on hemispherical carbon particles. The vertically interconnected 3-D GNSs on hemispherical carbon particles have been characterized by scanning electron microscopy, transmission electron microscopy, selective area electron diffraction pattern, X-ray diffraction, atomic force microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and nitrogen gas adsorption-Brunauer-Emmet-Teller. The present CVD approach is capable of producing large quantities of GNSs with high purity. Moreover, a high-purity free-standing and vertically interconnected 3-D GNSs on hemispherical carbon particles have an enormous potential for applications in electronic devices, biological sensors, gas uptake and storage, fuel cells, lithium ion batteries, and more.
Imaging specificity of MR-optical imaging agents following the masking of surface charge by poly(ethylene glycol)
(2013-05-01)
Wu, Shou-Cheng
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Lin, Kun-Liang
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Wang, Tzu-Pin
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Tzou, Shey-Cherng
;
Singh, Gyan
The coupling of specific antibodies to imaging agents often improves imaging specificity. However, free amine groups designed for the coupling can cause nonspecific binding of the imaging agents. We report here development of a nanocarrier, MnMEIO-silane-NH2-mPEG nanoparticles (NPs), consisting of a manganese-doped iron oxide nanoparticle core (MnMEIO), a copolymer shell of silane and amine-functionalized poly(ethylene glycol) (silane-EA-mPEG). The key feature in MnMEIO-silane-NH2-mPEG is the flexible PEG, which masks the non-conjugated reactive amine groups (-NH2 <-> -NH3+) and reduces nonspecific binding of MnMEIO-silane-NH2-mPEG to cells. The amine groups on MnMEIO-silane-NH2-mPEG were conjugated with the fluorescent dye, Cy777 or antibodies [Erbitux (Erb)] to form a MR-optical imaging contrast agent (MnMEIO-silane-NH2-(Erb)-mPEG) for EGFR-expressing tumors. Confocal microscopic and flow cytometric analyses showed that MnMEIO-silane-NH2-(Erb)-mPEG displayed low nonspecific binding. Moreover, TEM images showed that MnMEIO-silane-NH2-(Erb)-mPEG were endocytosed by EGFR-expressing cells. In line with their EGFR expression levels, A431, PC-3, and Colo-205 tumors treated with MnMEIO-silane-NH2-(Erb)-mPEG NPs showed -97.1%, -49.7%, and -2.8% contrast enhancement, respectively, in in vitro T-2-weighted MR imaging. In vivo T-2-weighted MR imaging and optical images showed that MnMEIO-silane-NH2-(Erb)mPEG could specifically and effectively target to EGFR-expressing tumors in nude mice; the relative contrast enhancements were 7.94 (at 2 h) and 7.59 (at 24 h) fold higher in A431 tumors as compared to the EGFR-negative Colo-205 tumors. On the contrary, MnMEIO-silane-NH2-(Erb) NPs showed only 1.44 (at 2 h) and 1.52 (at 24 h) fold higher in EGFR-positive tumors as compared to the EGFR-negative tumors. Finally, antibodies can be readily changed to allow imaging of other tumors bearing different antigens. These data indicate that masking surface charges on contrast agents is a useful strategy to improve imaging efficacy. (c) 2013 Elsevier Ltd. All rights reserved.
Nitric Oxide Turn-on Fluorescent Probe Based on Deamination of Aromatic Primary Monoamines
(2012-05-07)
Shiue, Tsun-Wei
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Chen, Yen-Hao
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Wu, Chi-Ming
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Singh, Gyan
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Chen, Hsing-Yin
The stable, water-soluble, and nonfluorescent FA-OMe can sense nitric oxide (NO) and form the intensely fluorescent product dA-FA-OMe via reductive deamination of the aromatic primary amine. The reaction is accompanied by a notable increase of the fluorescent quantum yield from 1.5 to 88.8%. The deamination mechanism of FA-OMe with NO was proposed in this study. The turn-on fluorescence signals were performed by suppression of photoinduced electron transfer (PeT), which was demonstrated by density functional theory (DFT) calculations of the components forming FA-OMe and dA-FA-OMe. Furthermore, FA-OMe showed water solubility and good stability at physiological pHs. Moreover, the selectivity study indicated that FA-OMe had high specificity for NO over other reactive oxygen/nitrogen species. In an endogenously generated NO detection study, increasing the incubation time of FA-OMe with lipopolysaccharide (LPS) pretreated Raw 264.7 murine macrophages could cause an enhanced fluorescence intensity image. In addition, a diffusion/localization cell imaging study showed that FA-OMe could be trapped in Raw 264.7 cells. These cell imaging results demonstrated that FA-OMe could be used as a turn-on fluorescent sensor for the detection of endogenously generated NO.
Recent progress in the development of anode and cathode catalysts for direct methanol fuel cells
(2013-09-01)
Tiwari, Jitendra N.
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Tiwari, Rajanish N.
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Singh, Gyan
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Kim, Kwang S.
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生物科技學系
Continuous growth in global energy demand has sparked concerns about energy security and environmental sustainability. In the past two decades, attempts have been made in the development of innovative energy technologies. The direct methanol fuel cell (DMFC) is among the most promising alternative energy sources for the near future. Simple construction, compact design, high energy density and relatively high energy-conversion efficiency give the DMFC an advantage over other promising power sources in terms of portability. However, the translation of DMFCs into commercially successful products is precluded due to poor performance. In addition, low activity, poor durability and reliability and an expensive anode and cathode further discourage the application of DMFCs. In this regard, the present review article focuses on recent progress in the development of anode and cathode catalysts for DMFCs. The first part of the review discusses the recent developments in the synthesis of single-, double-, and multiple-component catalysts and new catalyst supports for anode electrodes. The section is followed by the chemical approaches employed to make alloys and composite catalysts, aiming to enhance their activity, reliability and durability for the methanol oxidation reaction. Finally, exciting new research that pushes the development of single-, double-, and multiple-component catalysts and new catalyst supports for cathode electrodes is introduced. In addition, size-, shape- and composition-dependent electrocatalysts that are advocated for methanol oxidation at the anode and oxygen reduction at the cathode are highlighted to illustrate the potential of the newly developed electrocatalysts for DMFC applications. Moreover, this article provides a comprehensive review of the experimental work that is devoted to understanding the fundamental problems and recent progress in the development of anode and cathode catalysts for DMFCs. (C) 2013 Elsevier Ltd. All rights reserved.
Synthesis and Physicochemical Characterization of Carbon Backbone Modified [Gd(TTDA)(H(2)O)](2-) Derivatives
(2011-02-21)
Chang, Ya-Hui
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Chen, Chiao-Yun
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Singh, Gyan
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Chen, Hsing-Yin
;
Liu, Gin-Chung
The present study was designed to exploit optimum lipophilicity and high water-exchange rate (k(ex)) on low molecular weight Gd(III) complexs to generate high bound relaxivity (r(1)(b)), upon binding to the lipophilic site of human serum albumin (HSA). Two new carbon backbone modified TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid) derivatives, CB-TTDA and Bz-CB-TTDA, were synthesized. The complexes [Gd(CB-TTDA)(H(2)O)](2-) and [Gd(Bz-CB-TTDA)(H(2)O)](2-) both display high stability constant (log K(GdL) = 20.28 and 20.09, respectively). Furthermore, CB-TTDA (log K((Gd/Zn)) = 4.22) and Bz-CB-TTDA (log K((Gd/Zn)) = 4.12) exhibit superior selectivity of Gd(III) against Zn(II) than those of TTDA (log K((Gd/Zn)) = 2.93), EPTPA-bz-NO(2) (log K((Gd/Zn)) = 3.19), and DTPA (log K((Gd/Zn)) = 3.76). However, the stability constant values of [Gd(CB-TTDA)(H(2)O)](2-) and [Gd(Bz-CB-TTDA)(H(2)O)](2-) are lower than that of MS-325. The parameters that affect proton relaxivity have been determined in a combined variable temperature (17)O NMR and NMRD study. The water exchange rates are comparable for the two complexes, 232 x 10(6) s(-1) for [Gd(CB-TTDA)(H(2)O)](2-) and 271 x 10(6) s(-1) for [Gd(Bz-CB-TTDA)(H(2)O)](2-). They are higher than those of [Gd(TTDA)(H(2)O)](2-) (146 x 10(6) s(-1)), [Gd(DTPA)(H(2)O)](2-) (4.1 x 10(6) s(-1)), and MS-325 (6.1 x 10(6) s(-1)). Elevated stability and water exchange rate indicate that the presence of cyclobutyl on the carbon backbone imparts rigidity and steric constraint to [Gd(CB-TTDA)(H(2)O)](2-) and [Gd(Bz-CB-TTDA)(H(2)O)](2-). In addition, the major objective for selecting the cyclobutyl is to tune the lipophilicity of [Gd(Bz-CB-TTDA)(H(2)O)](2-). The binding affinity of [Gd(Bz-CB-TTDA)(H(2)O)](2-) to HSA was evaluated by ultrafiltration study across a membrane with a 30 kDa MW cutoff, and the first three stepwise binding constants were determined by fitting the data to a stoichiometric model. The binding association constants (K(A)) for [Gd(CB-TTDA)(H(2)O)](2-) and [Gd(Bz-CB-TTDA)(H(2)O)](2-) are 1.1 x 10(2) and 1.5 x 10(3), respectively. Although the K(A) value for [Gd(Bz-CB-TTDA)(H(2)O)](2-) is lower than that of MS-325 (K(A) = 3.0 x 10(4)), the r(1)(b) value, r(1)(b) = 66.7 mM(-1) s(-1) for [Gd(Bz-CB-TTDA)(H(2)O)](2-), is significantly higher than that of MS-325 (r(1)(b) = 47.0 mM(-1) s(-1)). As measured by the Zn(II) transmetalation process, the kinetic stabilities of [Gd(CB-TTDA)(H(2)O)](2-), [Gd(Bz-CB-TTDA)(H(2)O)](2-), and [Gd(DTPA)(H(2)O)](2-) are similar and are significantly higher than that of [Gd(DTPA-BMA)(H(2)O)](2-) High thermodynamic and kinetic stability and optimized lipophilicity of [Gd(CB-TTDA)(H(2)O)](2-) make it a favorable blood pool contrast agent for MRI.
Synthesis and Physicochemical Characterization of Carbon Backbone Modified [Gd(TTDA)(H2O)](2-) Derivatives
(2011-02-21)
Chang, Ya-Hui
;
Chen, Chiao-Yun
;
Singh, Gyan
;
Chen, Hsing-Yin
;
Liu, Gin-Chung
The present study was designed to exploit optimum lipophilicity and high water-exchange rate (k(ex)) on low molecular weight Gd(III) complexs to generate high bound relaxivity (r(1)(b)), upon binding to the lipophilic site of human serum albumin (HSA). Two new carbon backbone modified TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid) derivatives, CB-TTDA and Bz-CB-TTDA, were synthesized. The complexes [Gd(CB-TTDA)(H2O)](2-) and [Gd(Bz-CB-TTDA)(H2O)](2-) both display high stability constant (log K-GdL = 20.28 and 20.09, respectively). Furthermore, CB-TTDA (log K-(Gd/Zn) = 4.22) and Bz-CB-TTDA (log K-(Gd/Zn) = 4.12) exhibit superior selectivity of Gd(III) against Zn(II) than those of TTDA (log K-(Gd/Zn) = 2.93), EPTPA-bz-NO2 (log K-(Gd/Zn) = 3.19), and DTPA (log K-(Gd/Zn) = 3.76). However, the stability constant values of [Gd(CB-TTDA)(H2O)](2-) and [Gd(Bz-CB-TTDA)(H2O)](2-) are lower than that of MS-325. The parameters that affect proton relaxivity have been determined in a combined variable temperature O-17 NMR and NMRD study. The water exchange rates are comparable for the two complexes, 232 x 10(6) s(-1) for [Gd(CB-TTDA)(H2O)](2-) and 271 x 10(6) s(-1) for [Gd(Bz-CB-TTDA)(H2O)](2-). They are higher than those of [Gd(TTDA)(H2O)](2-) (146 x 10(6) s(-1)), [Gd(DTPA)(H2O)](2-) (4.1 x 10(6) s(-1)), and MS-325 (6.1 x 10(6) s(-1)). Elevated stability and water exchange rate indicate that the presence of cyclobutyl on the carbon backbone imparts rigidity and steric constraint to [Gd(CB-TTDA)(H2O)](2-) and [Gd(Bz-CB-TTDA)(H2O)](2-). In addition, the major objective for selecting the cyclobutyl is to tune the lipophilicity of [Gd(Bz-CB-TTDA)(H2O)](2-). The binding affinity of [Gd(Bz-CB-TTDA)(H2O)](2-) to HSA was evaluated by ultrafiltration study across a membrane with a 30 kDa MW cutoff, and the first three stepwise binding constants were determined by fitting the data to a stoichiometric model. The binding association constants (K-A) for [Gd(CB-TTDA)(H2O)](2-) and [Gd(Bz-CB-TTDA)(H2O)](2-) are 1.1 x 10(2) and 1.5 x 10(3), respectively. Although the K-A value for [Gd(Bz-CB-TTDA)(H2O)](2-) is lower than that of MS-325 (K-A = 3.0 x 10(4)), the r(1)(b) value, r(1)(b) = 66.7 mM(-1) s(-1) for [Gd(Bz-CB-TTDA)(H2O)](2-), is significantly higher than that of MS-325 (r(1)(b) = 47.0 mM(-1) s(-1)). As measured by the Zn(II) transmetalation process, the kinetic stabilities of [Gd(CB-TTDA)(H2O)](2-), [Gd(Bz-CB-TTDA)(H2O)](2-), and [Gd(DTPA)(H2O)](2-) are similar and are significantly higher than that of [Gd(DTPA-BMA)(H2O)](2-) High thermodynamic and kinetic stability and optimized lipophilicity of [Gd(CB-TTDA)(H2O)](2-) make it a favorable blood pool contrast agent for MRI.