Journal of Materials Chemistry B
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2016
·Vol. 4
·期 45
·7241-7248
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IF 4.872
Qin Zhu,Heng Yang,Yuanyuan Li,Yu Tian,Wei Wang,Weijun Tang,Yuan Yuan,Aiguo Hu
HP-DO3A-based cationic amphiphilic Gd(III) complexes bearing quaternary ammonium salts of different alkyl chain lengths were synthesized. The structures of the intermediates, the ligands and the Gd(III) complexes were characterized by 1H NMR, 13C NMR, ESI and MALDI-TOF mass spectrometry. Relaxation studies of the amphiphilic Gd(III) complexes revealed that long alkyl chains facilitated the formation of micelles in an aqueous solution and afforded high relaxivity. Electrostatic self-assembly of the GdL1 complex with polyacrylate sodium (PAAS) showed significant relaxation enhancement with the relaxivity being up to 20.03 mM−1 s−1 at 1.5 T, which was about 4 times that of the commercial MRI contrast agent, Gd-DTPA. The long hydrophobic chain was found to play an important role in the formation of the self-assembly. Zeta potential and dynamic light scattering measurements were carried out to reveal the aggregation process during the assembly. Good biocompatibility of the complexes and high cell viability were found in HepG-2 and L-02 cells by the MTT assay. The reactive oxygen species (ROS) generation study further confirmed the biocompatibility. In vivo imaging showed significant contrast enhancement in the liver and bladder regions.
研究领域:
医学影像学
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材料科学
·
生物化学
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DOI
PubMed
高影响因子
POLYHEDRON
·
2018
·
IF 2.067
Fuxian Wan,Lipeng Wang,Wenxin Xu,Changcheng Li,Ying Li,Chunbao Zhang,Lin Jiang
A novel dimeric gadolinium(III) complex, bis(4-Gd-DTPA-aminophenyl)adamantane ( 5 ), was successfully synthesized using bis(4-aminophenyl)adamantane to link two Gd-DTPA units. All the intermediates and bis(4-Gd-DTPA-aminophenyl)adamantane ( 5 ) have been characterized by 1 H NMR, 13 C NMR, ES-API-MS, HR-ESI-MS, FT-IR and elemental analysis (EA). The longitudinal relaxivity of bis(4-Gd-DTPA-aminophenyl)adamantane is 8.43 mM −1 Gd −1 s −1 at 0.43 T (32 °C, pH 7.0), and 4.89 mM −1 Gd −1 s −1 at 3.0 T (32 °C, pH 7.4). The T 1 -weighted imaging in vitro showed that bis(4-Gd-DTPA-acetylaminophenyl)adamantane can enhance the contrast of images distinctly. But most of all, the kinetic inertness of bis(4-Gd-DTPA-aminophenyl)adamantane ( 5 ) was comparable to that of [Gd(DTPA)(H 2 O)] 2− (Magnetvist®). Moreover, cytotoxicity tests indicated that the bis(4-Gd-DTPA-acetylaminophenyl)adamantane exhibited low toxicity to healthy liver cells (L-02 cells). These results demonstrate that the Gd(III) complex 5 may be a promising MRI contrast agent candidate.
研究领域:
医学影像学
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化学
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DOI
高影响因子
Science of Advanced Materials
·
2021
·Vol. 13
·期 9
·1611-1621
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IF 1.474
Guo Rong,Ma Binbin,Nie Jiaqiu
This study aimed to explore the value of preoperative mammography in the differential diagnosis of benign and malignant tumors of nipple discharge. A biocompatible T1 contrast agent KMnF3 nanoparticle was first developed in the research, and then RGD-coupled KMnF3
nanoparticles were further synthesized as a highly sensitive tumor-targeted magnetic resonance imaging (MRI) contrast agent. While the nanoparticle was characterized physically, cytotoxicity test and MRI test in breast cancer mice were performed, and the excised tumors were subjected to immunostaining
and tumor electron microscope section processing. At the same time, 60 patients with nipple discharge were screened to participate in the research, and the prepared MRI nano contrast agent was used for the differential diagnosis of breast benign/malignant tumors of nipple discharge. In the
experiment, the synthetic nanoparticles were tested by Fourier transformed infrared (FTIR), which proved that the designed RGDtu/KMnF3 nanoparticles were successfully synthesized. The quantitative analysis of the synthesized nanoparticles showed that the relaxation efficiency reached
23.12 mM−1s−1, and there was no obvious toxicity. After staining, the microscope showed that the tumor was proliferating. After intravenous injection of low-dose RGDtu/KMnF3 contrast agent, nanoparticles were found in the tumor tissue. It was found
that the synthesized nanoparticles enhanced the contrast of tumors with a volume of less than 50 mm3 by observing tumor slices. The imaging of the patient’s breast showed that the X-ray classification of galactography based on this contrast agent was statistically significant
in distinguishing benign/malignant lesions of nipple discharge (X
2 = 58.700, P < 0.01).
研究领域:
医学影像学
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生物材料学
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肿瘤学
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DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
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2017
·Vol. 36
·期 3
·391-398
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IF 1.692
Wang Hao,Dai Ting-Ting,Lu Bo-Lun,Li Sheng-Li,Lu Qing,Mukwaya Vincent,Dou Hong-Jing
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 (r1) 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.
研究领域:
生物医学工程
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医学影像学
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DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
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2021
·Vol. 56
·期 12
·7386-7396
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IF 4.22
Zhou Weixiu,Shen Jiyun,Lin Jiaomin,An Miao,An Lu,Tian Qiwei,Yang Shiping
Gd–chelate magnetic resonance imaging (MRI) contrast agents used in conventional clinical medicine still have some shortcomings, such as their low relaxation rates and poor imaging sensitivity. In this work, a Gd–chelate (Gd–DTPA), with a comparison made to the commercial contrast agent Magnevist was loaded into a zeolitic imidazolate framework (ZIF-8) to construct the efficient T 1 MRI contrast agent Gd–DTPA@ZIF-8. At 0.5 T, the longitudinal relaxivity value ( r 1 ) of Gd–DTPA@ZIF-8 reaches 29.60 mM −1 s −1 , which is about 6 times higher than that of Gd–DTPA. In terms of the retention of Gd–DTPA in ZIF-8, no obvious Gd 3+ ions are released in water and complete culture solution over a long time period. Haemolysis and cytotoxicity experiments revealed that Gd–DTPA@ZIF-8 has good biocompatibility. In addition, the in vivo MRI results prove that Gd–DTPA@ZIF-8 can significantly enhance the T 1 -weighted MRI contrast effect of the tumour site. These advantages make Gd–DTPA@ZIF-8 a potential candidate for biomedical applications.
研究领域:
医学影像学
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材料科学
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纳米医学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 41
·6716-6725
·
IF 4.872
Yi Cao,Min Liu,Kunchi Zhang,Jingjin Dong,Guangyue Zu,Yang Chen,Tingting Zhang,Dangsheng Xiong,Renjun Pei
Macromolecular contrast agents (CAs) labeled with targeting molecules are gaining remarkable interest as promising materials overcoming the defects of small-molecule CAs. Designed on the basis of biocompatible poly(glycerol) (PG), a linear macromolecular contrast agent (CA) was synthesized with a composition of PG as a backbone and partial hydroxyl connected with gadolinium labeled poly(L-lysine) dendrons, where folic acid was also conjugated. This linear CA exhibited higher relaxivity (7.04 mM−1 S−1) relative to Magnevist® (3.98 mM−1 S−1), and showed negligible toxicity determined by WST assay and histological analysis. In vitro and in vivo magnetic resonance imaging (MRI) measurements presented obvious target specificity to KB cells and tumor. Moreover, high signal enhancement was observed in the tumor region at various time points after intravenous injection to ensure the long time window for imaging. All the findings make it an attractive candidate for tumor-targeted MRI CAs.
研究领域:
生物医学工程
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医学影像学
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材料科学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
·
IF 4.152
Haitao Huang,Tao Yue,Ke Xu,Jafar Golzarian,Jiahui Yu,Jin Huang
Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd 3+ from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5 nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100 nm and a longitudinal relaxivity ( r 1 ) of 10.2 mM −1 S −1 . Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T 1 -weighted MRI diagnosis of tumor.
研究领域:
生物医学工程
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影像医学
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材料科学
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DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 34
·19397-19407
·
IF 3.049
Jie Yin,Guangfu Yin,Ximing Pu,Zhongbing Huang,Dajin Yao
As desirable contrast agents for magnetic resonance imaging (MRI), ultrasmall superparamagnetic iron oxides (USPIOs) are required to exhibit both low cytotoxicity and specific targetability besides superparamagnetism to achieve better imaging contrast at lower dose, and cladding with biocompatible polymers and modification with targeting ligands are considered to be the most effective strategies. In this study, novel dextran wrapped and peptide WSGPGVWGASVK (peptide-WSG) grafted USPIOs were meticulously prepared and systematically characterized. Firstly, dextran (Dex) cladded USPIOs (USPIOs@Dex) were synthesized with a well-designed co-precipitation procedure in which the biocompatible dextran played dual roles of grain inhibitor and cladding agent. After that, sodium citrate was applied to carboxylize the hydroxyls of the dextran molecules via an esterification reaction, and then tumor targeting peptide-WSG was grafted to the carboxyl groups by the EDC method. The XRD, TEM, and FTIR results showed that inverse spinel structure Fe3O4 crystallites were nucleated and grown in aqueous solution, and the catenulate dextran molecules gradually bound on their surface, meanwhile the growth of grains was inhibited. The size of original crystallite grains was about 7 nm, but the mean size of USPIOs@Dex aggregates was 165.20 nm. After surface modification by sodium citrate and peptide-WSG with ultrasonic agitation, the size of the USPIOs@Dex-WSG aggregates was smaller (66.06 nm) because the hydrophilicity was improved, so USPIOs@Dex-WSG could evade being eliminated by RES more easily, and prolong residence time in blood circulation. The VSM and T2-weighted MRI results showed that USPIOs@Dex-WSG were superparamagnetic with a saturation magnetization of 44.65 emu g−1, and with high transverse relaxivity as the R2 relaxivity coefficient value was 229.70 mM−1 s−1. The results of MTT assays and the Prussian blue staining in vitro revealed that USPIOs@Dex-WSG exhibited nontoxicity for normal cells such as L929 and HUVECs, and were specifically targeted to the SKOV-3 cells. Thus, the novel dextran wrapped and WSG-peptide grafted USPIOs have potential to be applied as tumor active targeting contrast agents for MRI.
研究领域:
生物医学工程
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材料科学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE INDIAN CHEMICAL SOCIETY
·
2021
·
IF 0.284
Hao Guo,Songjie Fan,Jianhua Liu,Yumei Wang
With co-precipitation method we successfully synthesized an aqueous dispersible, superparamagnetic manganese ferrite nanoparticles at relatively low temperature (190 °C). This material shows potential application as T 2 MRI contrast agent. Cost-effective and less toxic manganese (II) chloride (MnCl 2 ·4H 2 O) and iron (III) chloride hexahydrate (FeCl 3 ·6H 2 O) were used as precursors and 2-[2-(2-Hydroxyethoxy)ethoxy] ethanol (TEG) were utilized as solvent which served as stabilizer and provided a reduction system. The mean diameter of these nanoparticles is about 7 nm. Its saturation magnetization (Ms) and relaxivity value (r 2 ) are as high as 46 emu/g and 593.9 mM −1 s −1 respectively. In vitro cell study demonstrated pancreatic cancer cells could keep viable when the manganese ferrite nanoparticles concentration reached up to 50 μg/mL.
研究领域:
材料科学
·
医学影像学
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产品关联
DOI
高影响因子
Small Methods
·
2022
·Vol. 6
·期 3
·2101145
·
IF 15.367
Zhilin Jiang,Bin Xia,Feng Ren,Bolin Bao,Wei Xing,Tao He,Zhen Li
Revealing the anatomical structures, functions, and distribution of vasculature via contrast agent (CA) enhanced magnetic resonance imaging (MRI) is crucial for precise medical diagnosis and therapy. The clinically used MRI CAs strongly rely on Gd-chelates, which exhibit low T 1 relaxivities and high risks of nephrogenic systemic fibrosis (NSF) for patients with renal dysfunction. It is extremely important to develop high-performance and safe CAs for MRI. Herein, it is reported that ultra-small NaGdF 4 nanoparticles (UGNs) can serve as an excellent safe MRI CA via surface engineering with rationally designed novel hydrophilic block co-polymer (BP n ). By optimizing the polymer molecular weights, the polymer-functionalized UGNs (i.e., UGNs-BP 14 ) are obtained to exhibit remarkably higher relaxivity (11.8 m m –1 s –1 at 3.0 T) than Gd-DTPA (3.6 m m –1 s –1 ) due to their ultracompact and abundant hydrophilic surface coating. The high performance of UGNs-BP 14 enables us to sensitively visualize microvasculature with a small diameter of ≈0.17 mm for up to 2 h, which is the thinnest blood vessel and the longest time window for low field (1.0 T) MR angiography ever reported, and cannot be achieved by using the clinically used Gd-DTPA under the same conditions. More importantly, renal clearable UGNs-BP 14 show lower risks of inducing NSF in comparison with Gd-DTPA due to their negligible release of Gd 3+ ions after modification with the novel hydrophilic block copolymer. The study presents a novel avenue for boosting imaging-performance and systemic biosafety of UGNs as a robust MRI CA with great potential in precise diagnosis of vasculature-related diseases.
研究领域:
医学影像学
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纳米医学
·
分子生物学
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DOI
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Jiali Li,Xue Jiang,Lihuan Shang,Zhen Li,Conglian Yang,Yan Luo,Daoyu Hu,Yaqi Shen,Zhiping Zhang
This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn2+ nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both in vitro and in vivo. Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The in vitro relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH = 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated in vitro using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the r1 relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM−1·s−1. Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, p=.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.
研究领域:
医学影像学
·
纳米医学
·
生物材料
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产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2024
·
IF 3.7
Songhan Hu,Mingyuan Ma,Rui Liang,Xinxin Xu,Kai Wang,Qiang Wang
Ferrite nanoparticles are widely used in magnetic resonance imaging as T 2 contrast agent particles. In this study, we propose to utilize Mn and Zn doping into ferrite to prepare Mn-Zn doped ferrite and use it as T 2 contrast agent core particles. Also, we aim to clarify the relationship between the Mn-Zn doped ferrite nanoparticles orientation and ratio of surfactant oleic acid to oleylamine as well as different solvents. The results show that high temperature thermal decomposition method can successfully prepare uniformly doped Mn-Zn ferrite nanoparticles (Mn 0.6 Zn 0.4 Fe 2 O 4 ). And the ratio of surfactant oleic acid to oleylamine has a significant impact on the orientation of Mn 0.6 Zn 0.4 Fe 2 O 4 nanoparticles growth. As the ratio of oleic acid increases, the Mn 0.6 Zn 0.4 Fe 2 O 4 nanoparticles gradually change from growing along the [110] crystal direction to growing randomly with irregular orientation, the nanoparticles morphology and size tend from rhombohedral (37 nm) to spherical (9.84 nm). In terms of solvent, benzyl ether, 1-octadecene and hexadecylamine have no influence on the action of surfactants. The Mn 0.6 Zn 0.4 Fe 2 O 4 nanoparticles in the three solvents are grown randomly without any obvious orientation changes. All nanoparticles are spherical nanoparticles, indicating that the choice of the three solvents has little effect on the orientation of the nanoparticles. However, the three different solvents affect the crystallinity of Mn 0.6 Zn 0.4 Fe 2 O 4 nanoparticles. Nanoparticles prepared with diphenyl ether as solvent show a higher crystallinity compared to those synthesized with 1-octadecene and hexadecylamine as solvents. In contrast performance, under the optimal surfactant ratio (11:1) and solvent selection (dibenzyl ether), the transverse relaxation rate r 2 value of Mn-Zn ferrite nanoparticles reach 266.24 mM −1 s −1 , while the longitudinal relaxation rate r 1 value is 10.45 mM −1 s −1 . The r 2 / r 1 ratio is significantly larger than 10, indicating that the nanoparticles with random growth orientation serve as excellent T 2 weighted contrast agents.
研究领域:
材料科学
·
医学影像学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）