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CHEMBIOCHEM · 2019 ·Vol. 21 ·期 6 ·865-873 · IF 2.641

Injectable Ovalbumin-Based Composite Implant for Photothermal Tumor Therapy

Jing Zhang,Xiao An,Yuting Zheng,Yongkang Chen,Chenyao Wu,Shige Wang

Graphical Hardboiled : A multifunctional hydrogel implant based on ovalbumin has been designed that can simultaneously deliver a photothermal transducing agent (polydopamine) and a chemotherapeutic (doxorubicin) and/or a contrast agent (iohexol) to tumors. It is anticipated that the multifunctional implant, not showing obvious toxicity to healthy tissue, could be a promising system for synergistic cancer treatment. Polymeric hydrogels with three-dimensional network structures have found tremendous applications in biomedicine. Herein, we report the synthesis of a multifunctional implant based on ovalbumin (OVA) as a carrier capable of synergistically delivering a photothermal transducing agent (polydopamine, PDA) to tumors. The formation of PDA was achieved by utilizing the basicity of OVA, whereas the formation of the hydrogel implant was achieved through the in vitro/in vivo near-infrared (NIR) laser-induced hyperthermia of PDA. The as-prepared PDA@OVA implant exhibits high photothermal conversion efficiency (38.7 %). Once implanted in vivo, the OVA-based implant shows great versatility in the treatment of malignant tumors. Furthermore, a chemotherapeutic (doxorubicin, DOX) and a contrast agent (iohexol), dispersed in the OVA solution in advance, can also be firmly entrapped in the hydrogel along with the hydrogel formation. It is anticipated that the multifunctional OVA-based implant, not showing any obvious toxicity to healthy tissue, could be a promising system for synergistic cancer treatment.

研究领域: 生物医学 · 肿瘤学 · 材料科学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Enhanced sensitivity of spectral CT imaging in vivo by using Ytterbium chelate

Chunmei Yang,Didi Gu,Xin Zhu,Pan Han,Liping Pan,Xiaoling Che,Xinyao Chen,Qiuyu Meng,Guidong Dai,Lu Yang

Spectral CT can overcome the shortcomings of conventional CT, however, clinically used iodized contrast agents are not ideal for spectral CT imaging, which calls for the development of novel contrast agent with high attenuation coefficient. In this study, a small molecule lanthanide chelate Ytterbium-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Yb-DOTA) was prepared by a simple and green one-step method, and it had multi-advantages such as good stability, excellent biocompatibility and high performance of spectral CT imaging in vitro and in vivo. In addition, Yb-DOTA had more prominent ability to visualize renal tissue, GI tract, the heart and venous system in both conventional and spectral CT imaging compared with clinical iohexol. Moreover, higher tissue contrast and enhanced sensitivity were achieved at high monochromatic energies (70–150 keV) after Yb-DOTA administration, indicating its superior spectral CT imaging performance. Yb-DOTA is expected to be a novel contrast agent to enhance the diagnostic sensitivity and accuracy.

CAS / MDL: 1611-35-4
研究领域: 医学影像学 · 分子影像 · 生物医学工程
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MEDICAL PHYSICS · 2024 · IF 3.2

Changes in the relaxivity of water-organic solvent miscible systems: Hidden forces beyond metal ions

Shiman Wu,Chaochao Wang,Junjie Xia,Dijia Sun,Pu-Yeh Wu,Yue Wu,Zhenwei Yao,Yan Ren,Qi Zhang

Background The relaxivity of magnetic resonance imaging (MRI) contrast agents is primarily attributed to metal ions such as gadolinium (Gd) and iron. However, the impact of organic solutes on relaxivity, particularly through alterations in water molecule dynamics, has not been thoroughly investigated. This research was aimed to explore how organic solutes affect the relaxivities of water and Gd-based contrast agents (GBCAs), potentially revealing new aspects for the development of contrast agents. Purpose To investigate the effects of different proportions of water-soluble organic solvents mixed with pure water and GBCA on T 1 and T 2 relaxivities. Methods Ethanol, dimethyl sulfoxide (DMSO), 1,4-dioxane, glycerin, ethylene glycol, diethylene glycol, polyethylene glycol (PEG) 200, and PEG 400 were mixed with ultrapure water in various ratios (100:0, 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, 10:90, 0:100). GBCA was added to these mixtures at a concentration of 0.05 mmol/L. The mixtures underwent T 1 and T 2 mapping scans using a 3.0 Tesla MRI machine, and the relaxivities R 1 (1/T 1 ) and R 2 (1/T 2 ) were calculated and compared. Results The relaxivity R 1 of ethanol, 1,4-dioxane, and DMSO mixtures with water or GBCA, as well as R 2 of DMSO mixtures with GBCA, initially increased and then decreased. Conversely, R 1 and R 2 increased significantly with higher proportions of diethylene glycol, PEG 200, and glycerin in the mixtures with GBCA. The increase in relaxivity R 1 was correlated with greater viscosity. When the proportion of DMSO and diethylene glycol exceeded 20%, minimal variability in R 2 was observed as the water content decreased. Conclusions Adding organic solvents to water and paramagnetic relaxation reagents could alter T 1 and T 2 relaxivities, suggesting potential new directions for modifying current contrast agents. Additionally, increasing the viscosity of the contrast agent was found to enhance the relaxivity.

研究领域: 医学影像学 · 生物物理学
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BIOMATERIALS · 2025 · IF 12.9

Large-scale synthesis of non-ionic bismuth chelate for computed tomography imaging in vivo

Yuping Zhang,Jianqi Deng,Mingbin Lang,Gang Shu,Jinbin Pan,Cai Zhang,Ran Cheng,Shao-Kai Sun

High atomic number elements-based X-ray computed tomography (CT) contrast agents offer a promising solution to address the inherent deficiencies of FDA-approved iodine contrast agents. However, they face substantial challenges in balancing imaging performance, safety, and large-scale production for clinical translation. Herein, inspired by the history of clinical gadolinium- and iodine-based contrast agents, we report a large-scale approach for synthesizing non-ionic bismuth (Bi) chelate for high-performance CT imaging in vivo . Bi-HPDO3A can be easily obtained from low-cost precursor within 4 steps at 6 g-scale. The non-ionic macrocyclic structure endows it with low osmolality, low viscosity, high stability, good renal clearable capability and biocompatibility. Additionally, Bi-HPDO3A realizes superior imaging performance across various in vivo applications, including gastrointestinal imaging, renal imaging, and computed tomography angiography (CTA). Especially, Bi-HPDO3A exhibits superior spectral imaging capability owing to the high K-edge of element Bi, achieving metal artifact-free CTA in vivo . The proposed Bi-HPDO3A that balances overall performance can serve as a high-performance CT contrast agent with potential for clinical translation.

CAS / MDL: 1304-76-3
研究领域: 医学影像学 · 放射医学 · 药学
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Materials Research Express · 2019 ·Vol. 6 ·期 9 ·095005 · IF 1.449

Economical synthesis of ultra-small Bi2S3 nanoparticles for high-sensitive CT imaging

Hui-Li Zhu,Qing-Yuan Cheng,Mei-Yan Liao,Zhi-Ling Zhang,Wei-Guo Cai,Jiao-Jiao Ma,Meng-Ying Sun,Ming-Xia Yu,Zhi-Quan Tian,Dai-Wen Pang

Ultra-small Bi2S3 nanoparticles are potential contrast agents for high-sensitive CT imaging. However, the expensive and harmful synthesis process limited their further application. Herein, an economical and low-toxic process was developed by employing S powders as sulfur precursors for large-scale preparation of ultra-small Bi2S3 nanoparticles. The as-prepared ultra-small Bi2S3 nanoparticles were modified with amine-terminated poly(ethylene glycol) (PEG) to produce water-soluble contrast agents. In vitro experiment results suggested that the ultra-small Bi2S3-PEG nanoparticles were low cytotoxic and superior contrast agents. In vivo experiments demonstrated that the ultra-small Bi2S3-PEG nanoparticles were preferred contrast agents for long-term and high-sensitive CT imaging.

研究领域: 医学影像学 · 纳米医学 · 生物材料
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JOURNAL OF THE CHINESE CHEMICAL SOCIETY · 2016 ·Vol. 63 ·期 12 ·977-984 · IF 0.879

Hydrothermal Synthesis of Monodispersed BaGdF5:Yb/Er Nanoparticles for CT and MR Imaging

Rongjin Sun,Ting Yin,Peng Huang,Guo Gao,Joseph George Shapter,Yulan Shen,Jingjing Zhang,Daxiang Cui

In this paper, we report the development of a facile one-pot hydrothermal method for the controlled synthesis of monodispersed BaGdF 5 :Yb/Er nanoparticles for computed tomography (CT) and magnetic resonance (MR) imaging. The as-prepared nanoparticles have uniform size with a diameter of 20–25 nm. MTT tests show that the cell viability surpasses 90% even with a concentration of nanoparticles of 500 µg/mL, suggesting that the as-prepared BaGdF 5 :Yb/Er nanoparticles possess low toxicity. For both BaGdF 5 :Yb/Er nanoparticles and iopromide, the Hounsfield unit (HU) values increase with the their concentration. The slope of BaGdF 5 :Yb/Er nanoparticles is about 26.47, which is much higher than that of iopromide (16.98), indicating a better CT imaging effect. Interestingly, we find that the synthesized BaGdF 5 :Yb/Er nanoparticles exhibit paramagnetism. Our in vitro and in vivo imaging experiments demonstrate that the synthesized monodispersed BaGdF 5 :Yb/Er nanoparticles can serve as effective contrast agents for CT and MR imaging.

研究领域: 材料科学 · 医学影像学 · 生物医学工程
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Journal of Nanomaterials · 2016 · IF 1.758

Micro-CT Imaging of RGD-Conjugated Gold Nanorods Targeting Tumor In Vivo

Xiaochao Qu,Xiaoxiao Li,Jingning Liang,Yanran Wang,Muhan Liu,Jimin Liang

Gold nanomaterials as computed tomography (CT) contrast agents at lower X-ray dosage to get a higher contrast have advantages of longer imaging time and lower toxic side effects compared to current contrast agents. As a receptor for Cyclo (Arg-Gly-Asp-D-Phe-Lys) (RGD) peptide, integrin is overexpressed on some tumor cells and tumor neovasculature. In this paper, we conjugated the RGD peptide on the surface of gold nanorods (AuNRs), designated as RGD-AuNRs, a promising candidate in applications such as tumor targeting and imaging capability for micro-CT imaging. Integrin -positive U87 cells and integrin -negative HT-29 cells were chosen to establish animal models relatedly and then texted the tumor targeting ability and imaging capability of RGD-AuNRs in vitro and in vivo. The MTT assay and stability measurement showed that RGD-conjugation eliminated their cytotoxicity and improved their biocompatibility and stability. Dark-field imaging of U87 cells and HT-29 cells testified the binding affinities and uptake abilities of RGD-AuNRs, and the results showed that RGD-AuNRs were more specifical to U87 cells. The enhanced micro-CT imaging contrast of intramuscular and subcutaneous injection illustrated the feasibility of RGD-AuNRs to be contrast agents. Furthermore, the micro-CT imaging of targeting U87 and HT-29 tumor models verified the targeting abilities of RGD-AuNRs.

CAS / MDL: 25952-53-8 106627-54-7
研究领域: 医学影像学 · 纳米生物学 · 肿瘤学
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Science of Advanced Materials · 2019 ·Vol. 11 ·期 12 ·1816-1824 · IF 1.158

The Performance of Composite Nanoparticles Based on Fe3O4@SiO2/PLGA/PFOB in Magnetic Resonance Imaging and Photoacoustic Imaging

Qin Huihao,Zhang Wei,Luo Yi,Wei Yubo,Sun Shenglu,Chen Jingya

Polylactic acid glycolic acid (PLGA), a polymer material, is used as a shell and perfluorooctane (PFOB) as the core. Fe3O4@SiO2 nanoparticles are distributed in the shell to prepare a magnetic phase change multifunctional nano emulsion contrast agent (Fe3O4@SiO2/PLGA/PFOB). The ultrasound, magnetic resonance imaging and CT imaging effects of the contrast agent on normal rat liver parenchyma are investigated. Methods: Single emulsification method is used to prepare Fe3O4@SiO2-loaded polymer Fe3O4@SiO2/PLGA/PFOB nanoparticles encapsulated with PLGA. In addition, polymer Fe3O4@SiO2/PLGA nanoparticles loaded with Fe3O4@SiO2 nanoparticles, PLGA@PFOB nanoparticles coated with PLGA and blank PLGA nanoparticles are prepared as experimental control group. Its surface morphology, internal structure, particle size, potential and other general characteristics are tested. RAW264.7 mouse mononuclear macrophages are cultured in vitro. Prussian blue staining is used to observe macrophage phagocytosis after Fe3O4@SiO2/PLGA/PFOB contrast agent is added to incubate for 3 hours. MTT method is used to detect the effect of contrast agent on cell activity. The macrophage suspension engulfed with Fe3O4-PFOB is examined by ultrasound, magnetic resonance and CT. The results showed that Fe3O4@SiO2/PLGA/PFOB is brown emulsion after being dissolved in double distilled water. Under the light microscope and scanning electron microscope, Fe3O4@SiO2/PLGA/PFOB is spherical, with regular shape, uniform size, good dispersity and smooth surface. Macrophages are dependent on the phagocytosis of the contrast medium without affecting the activity of macrophages. Moreover, in vitro imaging experiments, compared with the control group, macrophages phagocytized by Fe3O4@SiO2/PLGA/PFOB have obvious enhancement effects in ultrasound, magnetic resonance and CT imaging. In conclusion, Fe3O4@SiO2/PLGA/PFOB has good stability in vivo, can be engulfed by liver macrophages, and can enhance ultrasound, magnetic resonance and CT imaging of liver parenchyma. It is a safe and effective multifunctional ultrasound contrast agent.

研究领域: 医学影像学 · 材料科学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Hofmeister Effect-Based T1–T2 Dual-Mode MRI and Enhanced Synergistic Therapy of Tumor

Chuyao Chen,Cong Huang,Jiamin Liu,Jia Tao,Yuying Chen,Kan Deng,Yikai Xu,Bingquan Lin,Peng Zhao

The imaging resolution of magnetic resonance imaging (MRI) is influenced by many factors. The development of more effective MRI contrast agents (CAs) is significant for early tumor detection and radical treatment, albeit challenging. In this work, the Hofmeister effect of Fe2O3 nanoparticles within the tumor microenvironment was confirmed for the first time. Based on this discovery, we designed a nanocomposite (FePN) by loading Fe2O3 nanoparticles on black phosphorus nanosheets. After reacting with glutathione, the FePN will undergo two stages in the tumor microenvironment, resulting in the robust enhancement of r1 and r2 based on the Hofmeister effect in the commonly used magnetic field (3.0 T). The glutathione-activated MRI signal of FePN was higher than most of the activatable MRI CAs, enabling a more robust visualization of tumors. Furthermore, benefiting from the long circulation time of FePN in the blood and retention time in tumors, the synergistic therapy of FePN exhibited an outstanding inhibition toward tumors. The FePN with good biosafety and biocompatibility will not only pave a new way for designing a common magnetic field-tailored T1–T2 dual-mode MRI CA but also offer a novel pattern for the accurate clinical diagnosis and therapy of tumors.

研究领域: 医学影像学 · 纳米医学 · 肿瘤学
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RSC Advances · 2020 ·Vol. 10 ·期 31 ·18054-18061 · IF 3.119

An ultra-sensitive T2-weighted MR contrast agent based on Gd3+ ion chelated Fe3O4 nanoparticles

Jing Chen,Hui-Hui Xiang,Zu-Zhi Zhao,Yun-Kai Wu,Meng-Yu Fei,Meng-Meng Song

An ultra-sensitive T2-weighted MR imaging contrast agent was prepared based on Fe3O4 nanoparticles and Gd3+ ions (Fe3O4@Gd). Amino modified Fe3O4 nanoparticles were conjugated to diethylenetriamine pentaacetic acid, and finally coordinated with Gd3+ ions. The nanoparticles had a uniform morphology with a size of 100 nm and a Gd/Fe mass ratio of 1/110. The r2 (transverse relaxivity) of the Fe3O4 nanoparticles increased from 131.89 mM−1 s−1 to 202.06 mM−1 s−1 after coordination with Gd3+ ions. MR measurements showed that the aqueous dispersion of Fe3O4@Gd nanoparticles had an obvious concentration-dependent negative contrast enhancement. Hepatoma cells were selected to test the cytotoxicity and MR imaging effect. The application of Fe3O4@Gd nanoparticles as contrast agents was also exploited in vivo for T2-weighted MR imaging of rat livers. All the results showed the effectiveness of the nanoparticles in MR diagnosis.

研究领域: 医学影像学 · 纳米医学 · 生物材料学
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Theranostics · 2015 · IF 8.022

An Anion-Induced Hydrothermal Oriented-Explosive Strategy for the Synthesis of Porous Upconversion Nanocrystals

Peiyu Qiu,Rongjin Sun,Guo Gao,Chunlei Zhang,Bin Chen,Naishun Yan,Ting Yin,Yanlei Liu,Jingjing Zhang,Yao Yang,Daxiang Cui

Rare-earth (RE)-doped upconversion nanocrystals (UCNCs) are deemed as the promising candidates of luminescent nanoprobe for biological imaging and labeling. A number of methods have been used for the fabrication of UCNCs, but their assembly into porous architectures with desired size, shape and crystallographic phase remains a long-term challenging task. Here we report a facile, anion-induced hydrothermal oriented-explosive method to simultaneously control size, shape and phase of porous UCNCs. Our results confirmed the anion-induced hydrothermal oriented-explosion porous structure, size and phase transition for the cubic/hexagonal phase of NaLuF 4 and NaGdF 4 nanocrystals with various sizes and shapes. This general method is very important not only for successfully preparing lanthanide doped porous UCNCs, but also for clarifying the formation process of porous UCNCs in the hydrothermal system. The synthesized UCNCs were used for in vitro and in vivo CT imaging, and could be acted as the potential CT contrast agents.

研究领域: 材料科学 · 生物医学工程 · 纳米技术
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Journal of the Mechanical Behavior of Biomedical Materials · 2022 · IF 4.042

Exploring the use of enhanced cone-beam CT technique to diagnose vertical root fracture

Ziyang Hu,Xiao Pan,Yanni Hu,Shi Xu,Antian Gao,Dantong Cao,Zitong Lin

Objectives To explore the feasibility of using sodium iodide (NaI)+dimethyl sulfoxide (DMSO)+ethyl alcohol+ethyl acetate as a cone-beam CT (CBCT) contrast agent in the diagnosis of vertical root fracture (VRF). Methods 21 endodontically treated VRF teeth of 21 patients were collected in this study. All these 21 teeth were confirmed subtle fracture lines under transillumination, the number and position of fracture lines were recorded. All these patients had CBCT routine scanning (RS1) before extraction. After extraction, the teeth was performed micro-CT scanning and 3 in vitro CBCT scanning: CBCT routine scanning in vitro (RS2), CBCT enhanced scanning using meglumine diatrizoate (MD) as contrast agent(ES1); and CBCT enhanced scanning using NaI+DMSO+ethyl alcohol+ethyl acetate as contrast agent(ES2). The number of fracture lines was evaluated on all the 5 scanning modes and the accuracy of diagnosis was calculated. Results In all, there were 43 fracture lines on the 21 teeth. The accuracy of detection of fracture lines of CBCT RS1, RS2, ES1, ES2 and micro-CT was 0%, 20.9% (9/43), 11.6% (5/43), 93% (40/43) and 95.3% (41/43) respectively. Significant differences were found between ES2 vs. RS2, ES2 vs. ES1 ( p  < 0.01); however, no significant difference was found between ES2 vs. micro-CT ( p  > 0.05). Conclusion CBCT enhanced scanning using NaI+DMSO+ethyl alcohol+ethyl acetate as contrast agent could be a prospective technique in the diagnosis of VRF.

CAS / MDL: 64-17-5 67-68-5 141-78-6
研究领域: 牙医学 · 影像学
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