Novel Difolate Targeting Nano-Level Ultrasound Contrast Agent for Therapy of Breast Cancer Tumor Cells

2021 ◽  
Vol 13 (7) ◽  
pp. 1295-1303
Author(s):  
Guangheng Liu ◽  
Xiangfeng Yang ◽  
Qiming Niu ◽  
Wenkui Sun
Keyword(s):  
Breast Cancer ◽  
Contrast Agent ◽  
Tumor Cells ◽  
Folate Receptor ◽  
Ultrasound Contrast Agent ◽  
Hydroxyl Group ◽  
Binding Ability ◽  
Ultrasound Contrast ◽  
Mcf 7

ABSTRACTA new type of difolate targeting nano-level ultrasound contrast agent ((folate molecule, FOL)2-TUAs) was prepared, so as to investigate its targeted binding effect with human breast cancer mammary carcinoma cells (MCF-7) in vitro. L-2-aminoadipic acid (L-2-AD) as a branch unit was inserted at the hydroxyl end of distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH to construct a tree structure. At this time, the free hydroxyl group in the distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH structure modified the FOL with the help of N-Hydroxysuccinimide/N,N'-dicyclohexylcarbodiimide (NHS/DCC). Each 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DISP-PEG2000) connected two FOLs to generate difolate targeted nanomaterials. Nano laser particle size (PS) and Zeta potential analyzer (ZPA) were applied to analyze the physical characteristics of the material such as PS and dispersion, and the enhanced development effect in vitro was detected by the ultrasonic diagnostic instrument. Besides, the targeted binding ability of the contrast agent based on this material to folate receptor (FR) overexpressing MCF-7 cells was analyzed by flow cytometry (FCM) and fluorescence microscope. In the experiment, hydrogen-1 nuclear magnetic resonance (1H NMR) demonstrated that (FOL)2-TUAs was successfully synthesized. The surface of this material was round and uniformly distributed without aggregation. According to the relative number of FOL molecules, non-targeted nano-agent (U-TUA), monofolate targeted nano-agent (FOL-TUA), and difolate targeted nano-agent ((FOL)2-TUA) were obtained. The in vitro imaging showed that different materials exhibited enhanced imaging effects in ultrasonic diagnostic equipment. FCM and fluorescence microscopy both indicated that the difolate TUA could achieve a good binding to MCF-7 cells. Most of the nano-agents were attached to the cell membrane, surrounded by red fluorophore, namely increasing the FOL content of DISP-PEG2000 chain could enhance the targeted binding ability of tumor cells.

scholarly journals Preparation of anti-HER-2 antibody PLGA polymer nano- ultrasound contrast agent In vitro targeting experiment

2019 ◽  
Author(s):  
Ji Lin ◽  
Molly Stevens ◽  
John Smith
Keyword(s):  
Breast Cancer ◽  
Particle Size ◽  
Electron Microscope ◽  
Contrast Agent ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ultrasound Contrast Agent ◽  
Ultrasound Contrast ◽  
Her 2

AbstractIn this report, we demonstrated a novel method to prepare a hollow nano-targeted ultrasound contrast agent carrying anti-HER-2 antibody with high molecular weight polylactic acid-glycolic acid (PLGA) as a film-forming material, and to investigate in vitro targeting and imaging effects. We utilized the camphor as porogen, PLGA nano-ultrasound contrast agent was prepared by modified double emulsion solvent evaporation method. The general characteristics were characterized by scanning electron microscope, transmission electron microscope and laser particle size analyzer. The angiography was performed by carbodiimide method. The anti-HER-2 antibody was used to prepare the PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody. The in-situ imaging ability was evaluated by laser confocal scanning microscopy. Results indicate that the average particle size of PLGA nano-ultrasound contrast agent was (152.00± 58.08) nm. The particles were regular spherical, uniform in size and good in dispersion. In vitro targeting experiments showed that PLGA-targeted contrast agents with anti-HER-2 antibodies were more strongly aggregated on the surface of breast cancer cells. In vitro imaging experiments showed that the PLGA-targeted nano-ultrasound contrast imaging showed a fine and uniform point-like hyperechoic echo, and no significant attenuation of the posterior echo. This study successfully produced a PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody, which can specifically bind to breast cancer cells with high expression of HER-2 receptor in vitro, and the imaging effect in vitro is better.

In Vitro Evaluation of Ultrasound-Assisted Thrombolysis Using a Targeted Ultrasound Contrast Agent

2009 ◽  
Vol 31 (4) ◽  
pp. 235-246 ◽  
Author(s):  
Szu-Chia Chen ◽  
Jia-Ling Ruan ◽  
Po-Wen Cheng ◽  
Yueh-Hsun Chuang ◽  
Pai-Chi Li
Keyword(s):  
Contrast Agent ◽  
Weight Reduction ◽  
Ultrasound Contrast Agent ◽  
High Frequency Ultrasound ◽  
Ultrasound Frequency ◽  
Ultrasound Contrast ◽  
Targeted Ultrasound ◽  
Targeted Microbubbles ◽  
Ultrasound Assisted

A thrombus-targeted ultrasound contrast agent bound with tirofiban — a glycoprotein (GP) IIb/IIIa antagonist that can specifically bind to activated platelets in the thrombus — was designed to enhance both the image contrast and thrombolysis effect. In this study, we used 76 canine thrombi for investigation. The targeting ability to thrombi was confirmed by microphotography and high-frequency ultrasound (40 MHz) imaging. The effect of the targeted microbubbles on thrombolysis enhancement was investigated using an in vitro flow system: targeted and nontargeted microbubbles flowed through the clot for 30 seconds with a washing step; the microbubbles remained on the clot that were then cavitated by ultrasound (frequency = 1 MHz, MI = 1.2). The extent of thrombolysis was evaluated by weight reduction and histology analysis. The targeted microbubbles reduced the weight of thrombi by a factor of 1.7 times that of the nontargeted microbubbles. (clot weight reduction: 23.1 ± 5.3% versus 13.6 ± 4.9%, p < 0.01 between targeted and nontargeted group), and the signal enhancement was 3.34 ± 0.30 dB (mean ± SD, p < 0.01 compared to control). We conclude that targeted microbubbles are applicable not only for molecular imaging of thrombi but also for improving the effectiveness of ultrasound-assisted thrombolysis.

scholarly journals Evaluation of Microwave Ablation in 4T1 Breast Tumor by a Novel VEFGR2 Targeted Ultrasound Contrast Agents

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyu Li ◽  
Shujun Xia ◽  
Ri Ji ◽  
Weiwei Zhan ◽  
Wei Zhou
Keyword(s):  
Contrast Agent ◽  
Microwave Ablation ◽  
Average Particle Size ◽  
Ultrasound Contrast Agent ◽  
Ultrasound Contrast Agents ◽  
Tumor Ablation ◽  
Average Particle ◽  
Ultrasound Contrast ◽  
Ultrasound Signal

ObjectivesA novel ultrasound contrast agent (UCA) VEGFR2-targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) was prepared and applied in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation.MethodsVEGFR2-PEG-HSNs-Fe NPs were prepared by using nano-SiO2, which was regarded as a substrate and etched by ferrous acetate, and then modified with anti-VEGFR2 antibody. Laser confocal microscope and flow cytometry were used to observe its main physicochemical properties, and biological safety was also investigated. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by ultrasound by injecting VEGFR2-PEG-HSNs-Fe NPs.ResultsThe average particle size of VEGFR2-PEG-HSNs-Fe was 276.64 ± 30.31 nm, and the surface potential was −13.46 ± 2.83 mV. In vitro, the intensity of ultrasound signal increased with UCA concentration. Good biosafety was performed in in vivo and in vitro experiments. The enhanced ultrasound signal was detected in tumors after injection of VEGFR2-PEG-HSNs-Fe NPs, covering the whole tumor. The lesions, which were incompletely ablated, presented as contrast agent perfusion at the periphery of the tumor, and contrast enhanced ultrasound (CEUS) was performed again after complementary ablation. It was confirmed that all the lesions were completely ablated.ConclusionNano-targeted UCAs VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability of specific imaging, which might be used as a contrast agent in CEUS to evaluate the efficacy of tumor ablation.

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