Six new aminocarboxylic ligands were synthesized by reactions of EDTA (ethylenediaminetetraacetic acid) dianhydride or DTPA (dlethylenetriaminepenta-acetic acid) dianhydride and ethyl ester of serine,threonine and tyr...Six new aminocarboxylic ligands were synthesized by reactions of EDTA (ethylenediaminetetraacetic acid) dianhydride or DTPA (dlethylenetriaminepenta-acetic acid) dianhydride and ethyl ester of serine,threonine and tyrosine. Their paramagnetic metal complexes were also synthesized.All ligands and paramagnetic metal complexes were characterized by IR spectra,IH NMR and elemental analyses.Relaxivity study showed that the metal complexes had higher relaxation effectiveness as compared to corresponding unmodified metal complexes. Imaging study of gadolinium complex of tyrosine ethyl ester modified DTPA in mice demonstrated that this metal complex could apparently increase the signal intensity of MR images.展开更多
Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modi...Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modified with hydrazide, and the attachment of multiple chelated Gd（III） ions to the interior of the nano-suitcases affords nanoscale MRI contrast agents with high relaxivity values. The highly fenestrated dextran shell of the nano-suitcases assures water exchange which readily occurs between the surrounding environment and the Gd（III） ions encapsulated within the hybrid nano-suitcases. The complexation between the hydrophilic hydrazide interior of the nano-suitcases and Gd（III） ions results in an impressive Gd payload at 22.6 wt% in the hybrid nano-suitcases. The longitudinal relaxivity （rl） of the hybrid nano-suitcases is reported as 44.4 L/（mmol-s）, which is 9-14 folds of that of commercial Gd-DTPA agents. In vivo MRI studies demonstrate that the hybrid nano-suitcases accumulated in the lymph node of the rat due to their nanoscale dimensions and displayed strong signals in vivo. The results indicated that the hybrid nano-suitcases provide a promising platform for the diagnosis of lymph node related diseases.展开更多
Mn-TCPP-CSn（n=6,1 1,20） as a type of potential magnetic resonance imaging（MRI） contrast agents were synthesized via manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin（Mn-TCPP） modified with chitosan oligosa...Mn-TCPP-CSn（n=6,1 1,20） as a type of potential magnetic resonance imaging（MRI） contrast agents were synthesized via manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin（Mn-TCPP） modified with chitosan oligosaccharides（CSn）.Experimental data of infared（IR）,UV-Vis,MS,inductively coupled plasma-atomic emission spectrometer（ICP-AES） and size exclusion chromatography evidenced the formation of Mn-TCPP-CSn-The stability results show that Mn-TCPP-CSn in aqueous solution was stable enough to prevent Mn（Ⅱ） ions from leaking.The magnetic properties in vitro indicate that Mn-TCPP-CS20 possesses higher longitudinal relaxivity（r1=10.38 L·mmol^-1·s^-1） in aqueous solution than unmodified porphyrin Mn-TCPPNa4[manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin,tetrasodium salt]（r1=5.10 L·mmol^-1·s^-1） and the commercial contrast agent Gd-DTPA（r1=4.05 L·mmol^-1·s^-1）.The preliminary T1-weighted flash image studies in vitro show that the contrast and the imaging signal of Mn-TCPP-CSn were superior to those of Mn-TCPPNa4 and Gd-DTPA under the same conditions.The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay shows that Mn-TCPP-CSn has a good biocompatibility.In addition,the thermodynamical parameters（ΔH〈0,ΔS〈0,ΔG〈0） of Mn-TCPP-CSn bound to bovine serum albumin（BSA） show that Mn-TCPP-CSn could bind to BSA spontaneously,where the binding complex was stabilized mainly by van der Waals interactions and hydrogen bonds.These results suggest that Mn-TCPP-CSn have the advantage of becoming a potential MRI contrast agent.展开更多
Nitroreductases(NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide(NADH) as an electron donor. NTRs are present in a wide range of bacteri...Nitroreductases(NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide(NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T_1-weighted magnetic resonance imaging(MRI)contrast agent Gd-DOTA-PNB(probe 1) has been designed and explored for the possible detection of NTR.Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections.展开更多
Accurate diagnosis of hepatocellular carcinoma(HCC) in the early stage is vital for its treatment.Contrast-enhanced dynamic magnetic resonance imaging(MRI) performed in the presence of extracellular contrast agents su...Accurate diagnosis of hepatocellular carcinoma(HCC) in the early stage is vital for its treatment.Contrast-enhanced dynamic magnetic resonance imaging(MRI) performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions.However,the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage.The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired.The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions.In order to maximize lesion detection and characterization,novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles,nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent.In this review,the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed.Furthermore,liver target nanovectors aimed at improving the diagnostic accuracy of liver MRI by targeting additional features of focal liver lesions were highlighted.展开更多
Aiming at improving the sensitivity and accu- racy 9f diagnosis, the combination of magnetic resonance imaging （MRI） and X-ray computed tomography （CT） in a single probe is in urgent need. Here, we report the deve...Aiming at improving the sensitivity and accu- racy 9f diagnosis, the combination of magnetic resonance imaging （MRI） and X-ray computed tomography （CT） in a single probe is in urgent need. Here, we report the devel- opment of polyacrylic acid （PAA）-capped GdF3 nanoplates （NPs） as novel MRI and CT dual-mode contrast agents （CAs） with high longitudinal relaxivity （rl） and large X-ray attenuation coefficient. Uniform GdF3 rhombic NPs were fabricated by controlling reaction conditions and intro- ducing dopants. The average size of GdF3 NPs is （10.6 ：k 1.1） nm in long diagonal, （7.0 -t- 0.8） nm in short diagonal, and （4.2 -4- 1.2） nm in thickness. Ligand-exchange treat- ment was performed to render the NPs water-dispersible. The rl of PAA-capped GdF3 NPs （15.8 L/（mmol s）） is four times higher than that of clinically used Gd-DTPA. We suppose that the high r~ value originates from the con- struction of two-dimensional （2D） nanostructures, which endows nanocrystals with larger surface areas and longer rotational correlation time than those of sphere nanostruc- tures with the same volume. The CT contrast enhancement ability of PAA-capped GdF3 NPs was evaluated in com- parison with clinically used Iohexol. The above results suggest that the PAA-capped GdF3 NPs could serve as CAs for MRI and CT dual-mode imaging.展开更多
Two gadolinium polyoxometalates, KCs4[Gd（a-SiW11O39）].25HzO（POM-1） and K13[Gd（f12-SiWllO39）a]·27H2O（POM-2）, have been evaluated as the candidates of potential magnetic resonance imaging Tl（longitudinal r...Two gadolinium polyoxometalates, KCs4[Gd（a-SiW11O39）].25HzO（POM-1） and K13[Gd（f12-SiWllO39）a]·27H2O（POM-2）, have been evaluated as the candidates of potential magnetic resonance imaging Tl（longitudinal relaxation） contrast agents. Longitudinal relaxivities of POM-2 are much higher than those of POM-1 in pure water and protein solution, respectively. However, compared with POM-1, POM-2 interacts with protein more strongly through electrostatic interaction, which is comfirmed by the fluoresence quenching of human serum albumin（HSA） in solu- tions with different polyoxometalate concentrations. Meanwhile, POM-1 presentes much lower cytotoxicity in the cell viability tests.展开更多
Accurate diagnosis of hepatocellular carcinoma （HCC） in the early stage is vital for its treatment. Contrast-enhanced dynamic magnetic resonance imaging （MRI） performed in the presence of extracellular contrast ag...Accurate diagnosis of hepatocellular carcinoma （HCC） in the early stage is vital for its treatment. Contrast-enhanced dynamic magnetic resonance imaging （MRI） performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions. However, the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage. The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired. The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions. In order to maximize lesion detection and characterization, novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles, nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent. In this review, the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed. Furthermore, liver target nanovectors aimed at improving the diagnostic accuracy of liver MR1 by tar~etin~ additional features of focal liver lesions were highlighted.展开更多
文摘Six new aminocarboxylic ligands were synthesized by reactions of EDTA (ethylenediaminetetraacetic acid) dianhydride or DTPA (dlethylenetriaminepenta-acetic acid) dianhydride and ethyl ester of serine,threonine and tyrosine. Their paramagnetic metal complexes were also synthesized.All ligands and paramagnetic metal complexes were characterized by IR spectra,IH NMR and elemental analyses.Relaxivity study showed that the metal complexes had higher relaxation effectiveness as compared to corresponding unmodified metal complexes. Imaging study of gadolinium complex of tyrosine ethyl ester modified DTPA in mice demonstrated that this metal complex could apparently increase the signal intensity of MR images.
基金financially supported by the National Natural Science Foundation of China(Nos.21374061,81371703 and 81501571)the Marie Curie International Incoming Fellowship of the EU+2 种基金the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning“Shu Guang”project supported by Shanghai Municipal Education CommissionShanghai Education Development Foundation
文摘Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modified with hydrazide, and the attachment of multiple chelated Gd（III） ions to the interior of the nano-suitcases affords nanoscale MRI contrast agents with high relaxivity values. The highly fenestrated dextran shell of the nano-suitcases assures water exchange which readily occurs between the surrounding environment and the Gd（III） ions encapsulated within the hybrid nano-suitcases. The complexation between the hydrophilic hydrazide interior of the nano-suitcases and Gd（III） ions results in an impressive Gd payload at 22.6 wt% in the hybrid nano-suitcases. The longitudinal relaxivity （rl） of the hybrid nano-suitcases is reported as 44.4 L/（mmol-s）, which is 9-14 folds of that of commercial Gd-DTPA agents. In vivo MRI studies demonstrate that the hybrid nano-suitcases accumulated in the lymph node of the rat due to their nanoscale dimensions and displayed strong signals in vivo. The results indicated that the hybrid nano-suitcases provide a promising platform for the diagnosis of lymph node related diseases.
基金Supported by the National Natural Science Foundation of China（Nos.21261008, 21302071, 21171076）, and the Cooperation Project of Hainan International Science and Technology, China（No.KJHZ2014-05）.
文摘Mn-TCPP-CSn（n=6,1 1,20） as a type of potential magnetic resonance imaging（MRI） contrast agents were synthesized via manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin（Mn-TCPP） modified with chitosan oligosaccharides（CSn）.Experimental data of infared（IR）,UV-Vis,MS,inductively coupled plasma-atomic emission spectrometer（ICP-AES） and size exclusion chromatography evidenced the formation of Mn-TCPP-CSn-The stability results show that Mn-TCPP-CSn in aqueous solution was stable enough to prevent Mn（Ⅱ） ions from leaking.The magnetic properties in vitro indicate that Mn-TCPP-CS20 possesses higher longitudinal relaxivity（r1=10.38 L·mmol^-1·s^-1） in aqueous solution than unmodified porphyrin Mn-TCPPNa4[manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin,tetrasodium salt]（r1=5.10 L·mmol^-1·s^-1） and the commercial contrast agent Gd-DTPA（r1=4.05 L·mmol^-1·s^-1）.The preliminary T1-weighted flash image studies in vitro show that the contrast and the imaging signal of Mn-TCPP-CSn were superior to those of Mn-TCPPNa4 and Gd-DTPA under the same conditions.The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay shows that Mn-TCPP-CSn has a good biocompatibility.In addition,the thermodynamical parameters（ΔH〈0,ΔS〈0,ΔG〈0） of Mn-TCPP-CSn bound to bovine serum albumin（BSA） show that Mn-TCPP-CSn could bind to BSA spontaneously,where the binding complex was stabilized mainly by van der Waals interactions and hydrogen bonds.These results suggest that Mn-TCPP-CSn have the advantage of becoming a potential MRI contrast agent.
基金supported by Sino-German research project GZ 1271,Peking Union Medical College(PUMC)Youth Fund(No.3332016056),the Innovation Project of Shandong Academy of Medical Sciences
文摘Nitroreductases(NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide(NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T_1-weighted magnetic resonance imaging(MRI)contrast agent Gd-DOTA-PNB(probe 1) has been designed and explored for the possible detection of NTR.Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections.
基金New Century Excellent Talents in University (Grant No.NCET-08-0334)Independent Innovation Foundation of Shandong University(IIFSDU,Grant No.2010JC019).
文摘Accurate diagnosis of hepatocellular carcinoma(HCC) in the early stage is vital for its treatment.Contrast-enhanced dynamic magnetic resonance imaging(MRI) performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions.However,the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage.The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired.The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions.In order to maximize lesion detection and characterization,novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles,nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent.In this review,the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed.Furthermore,liver target nanovectors aimed at improving the diagnostic accuracy of liver MRI by targeting additional features of focal liver lesions were highlighted.
基金This work was supported by the National Natural Science Foundation of China （21425101, 21371011, 21331001） and the National Basic Research Program of China （2014CB643800）.
文摘Aiming at improving the sensitivity and accu- racy 9f diagnosis, the combination of magnetic resonance imaging （MRI） and X-ray computed tomography （CT） in a single probe is in urgent need. Here, we report the devel- opment of polyacrylic acid （PAA）-capped GdF3 nanoplates （NPs） as novel MRI and CT dual-mode contrast agents （CAs） with high longitudinal relaxivity （rl） and large X-ray attenuation coefficient. Uniform GdF3 rhombic NPs were fabricated by controlling reaction conditions and intro- ducing dopants. The average size of GdF3 NPs is （10.6 ：k 1.1） nm in long diagonal, （7.0 -t- 0.8） nm in short diagonal, and （4.2 -4- 1.2） nm in thickness. Ligand-exchange treat- ment was performed to render the NPs water-dispersible. The rl of PAA-capped GdF3 NPs （15.8 L/（mmol s）） is four times higher than that of clinically used Gd-DTPA. We suppose that the high r~ value originates from the con- struction of two-dimensional （2D） nanostructures, which endows nanocrystals with larger surface areas and longer rotational correlation time than those of sphere nanostruc- tures with the same volume. The CT contrast enhancement ability of PAA-capped GdF3 NPs was evaluated in com- parison with clinically used Iohexol. The above results suggest that the PAA-capped GdF3 NPs could serve as CAs for MRI and CT dual-mode imaging.
基金the Natural Science Foundation of Jilin Province,China
文摘Two gadolinium polyoxometalates, KCs4[Gd（a-SiW11O39）].25HzO（POM-1） and K13[Gd（f12-SiWllO39）a]·27H2O（POM-2）, have been evaluated as the candidates of potential magnetic resonance imaging Tl（longitudinal relaxation） contrast agents. Longitudinal relaxivities of POM-2 are much higher than those of POM-1 in pure water and protein solution, respectively. However, compared with POM-1, POM-2 interacts with protein more strongly through electrostatic interaction, which is comfirmed by the fluoresence quenching of human serum albumin（HSA） in solu- tions with different polyoxometalate concentrations. Meanwhile, POM-1 presentes much lower cytotoxicity in the cell viability tests.
基金Foundation items： New Century Excellent lalents in University （Grant No. NCET-08-0334） and Independent Innovation Foundation of Shandong University （IIFSDU, Grant No. 2010JC019）.
文摘Accurate diagnosis of hepatocellular carcinoma （HCC） in the early stage is vital for its treatment. Contrast-enhanced dynamic magnetic resonance imaging （MRI） performed in the presence of extracellular contrast agents such as gadolinium chelates is considered as a useful approach for detecting and characterizing focal liver lesions. However, the sensitivity and specificity of conventional MRI contrast agents are far from satisfaction for the detection and characterization of benign and malignant focal liver lesions in the early stage. The novel molecular contrast agents special for liver with relatively longer metabolic time and stable contrast effect in liver tissue are highly desired. The development of nanotechnology provides an unprecedented opportunity for the diagnostic detection rate of HCC and cell-surface receptor-targeted nanotechnology improves the specificity of the detection of focal liver lesions. In order to maximize lesion detection and characterization, novel gadolinium chelates loaded nanovectors including the solid lipid nanoparticles, nanocomplexes and polymeric nanoparticles have been used as biocompatible molecular MRI contrast agent. In this review, the characterization and the advantages/disadvantages of these Gd-loaded novel nanovectors used as molecular MRI contrast agents were discussed. Furthermore, liver target nanovectors aimed at improving the diagnostic accuracy of liver MR1 by tar~etin~ additional features of focal liver lesions were highlighted.
