Grafting of abciximab to a microbubble-based ultrasound contrast agent for targeting to platelets expressing GP IIb/IIIa – Characterization and in vitro testing

2008 ◽  
Vol 68 (3) ◽  
pp. 555-564 ◽  
Author(s):  
A DELLAMARTINA
2021 ◽  
Vol 13 (7) ◽  
pp. 1295-1303
Author(s):  
Guangheng Liu ◽  
Xiangfeng Yang ◽  
Qiming Niu ◽  
Wenkui Sun

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.


2009 ◽  
Vol 31 (4) ◽  
pp. 235-246 ◽  
Author(s):  
Szu-Chia Chen ◽  
Jia-Ling Ruan ◽  
Po-Wen Cheng ◽  
Yueh-Hsun Chuang ◽  
Pai-Chi Li

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyu Li ◽  
Shujun Xia ◽  
Ri Ji ◽  
Weiwei Zhan ◽  
Wei Zhou

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.


2010 ◽  
Vol 4 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Donghee Park ◽  
Jinhee Yoon ◽  
Jingam Park ◽  
Byungjo Jung ◽  
Hyunjin Park ◽  
...  

Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity® in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD).


Tumor Biology ◽  
2016 ◽  
Vol 37 (7) ◽  
pp. 8609-8619 ◽  
Author(s):  
Jinfeng Xu ◽  
Xinxin Zeng ◽  
Yingying Liu ◽  
Hui Luo ◽  
Zhanghong Wei ◽  
...  

1998 ◽  
Vol 81 (12) ◽  
pp. 58G-61G ◽  
Author(s):  
Evan C. Unger ◽  
Thomas P. McCreery ◽  
Robert H. Sweitzer ◽  
DeKang Shen ◽  
GuanLi Wu

Sign in / Sign up

Export Citation Format

Share Document