scholarly journals Thin-Shelled PEGylated Perfluorooctyl Bromide Nanocapsules for Tumor-Targeted Ultrasound Contrast Agent

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Arifudin Achmad ◽  
Aiko Yamaguchi ◽  
Hirofumi Hanaoka ◽  
Yoshito Tsushima

Shell thickness determines the acoustic response of polymer-based perfluorooctyl bromide (PFOB) nanocapsule ultrasound contrast agents. PEGylation provides stealth property and arms for targeting moieties. We investigated a modulation in the polymer formulation of carboxy-terminated poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide-co-glycolide)-block-polyethylene glycol (PLGA-b-PEG) to produce thin-shelled PFOB nanocapsules while keeping its echogenicity, stealth property, and active targeting potential. Polymer formulation contains 40% PLGA-PEG that yields the PEGylated PFOB nanocapsules of approximately 150 nm size with average thickness-to-radius ratio down to 0.15, which adequately hindered phagocytosis. Functionalization with antibody enables in vitro tumor-specific targeting. Despite the acoustic response improvement, the in vivo tumor accumulation was inadequate to generate an observable acoustic response to the ultrasound power at the clinical level. The use of PLGA and PLGA-PEG polymer blend allows the production of thin-shelled PFOB nanocapsules with echogenicity improvement while maintaining its potential for specific targeting.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Wang ◽  
Al Christopher De Leon ◽  
Reshani Perera ◽  
Eric Abenojar ◽  
Ramamurthy Gopalakrishnan ◽  
...  

AbstractUltrasound imaging is routinely used to guide prostate biopsies, yet delineation of tumors within the prostate gland is extremely challenging, even with microbubble (MB) contrast. A more effective ultrasound protocol is needed that can effectively localize malignancies for targeted biopsy or aid in patient selection and treatment planning for organ-sparing focal therapy. This study focused on evaluating the application of a novel nanobubble ultrasound contrast agent targeted to the prostate specific membrane antigen (PSMA-targeted NBs) in ultrasound imaging of prostate cancer (PCa) in vivo using a clinically relevant orthotopic tumor model in nude mice. Our results demonstrated that PSMA-targeted NBs had increased extravasation and retention in PSMA-expressing orthotopic mouse tumors. These processes are reflected in significantly different time intensity curve (TIC) and several kinetic parameters for targeted versus non-targeted NBs or LUMASON MBs. These, may in turn, lead to improved image-based detection and diagnosis of PCa in the future.


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.


2017 ◽  
Vol 36 (5) ◽  
pp. 941-953 ◽  
Author(s):  
Jean-Marc Hyvelin ◽  
Emmanuel Gaud ◽  
Maria Costa ◽  
Alexandre Helbert ◽  
Philippe Bussat ◽  
...  

2020 ◽  
Vol 12 (5) ◽  
pp. 725-732
Author(s):  
Fangfang Yu ◽  
Jiaping Li ◽  
Yan Yang ◽  
Yueyue Cheng ◽  
Xianwei Ni ◽  
...  

By using an organic framework to fabricate functional biomaterials, novel design and advanced biomedical applications of polymeric microbubbles for in vivo targeting and disease-oriented imaging of tumor vascularization can be developed. The present study describes novel synthetic protocols to fabricate RGD (Arginine-Glycine-Aspartic)-tagged αvβ3-targeted ultrasound microbubbles. The microbubbles were synthesized by emulsion polymerization techniques. Two types of microbubbles (MBs-1 and MBs-2) were obtained via biotin-streptavidin conjugation to poly(butyl cyanoacrylate) microbubbles (MBs-0) obtained by one-step synthesis in reverse order. The size distributions and surface zeta potentials were characterized. The results showed that the sizes of the MBs-2 were larger than that those of the MBs-1, and the MBs-2 showed decreased charge compared to MBs-1. In cell targeting studies, MBs-2 exhibited relatively stronger targeting affinity for αvβ3 integrins, while MBs-1 showed weaker targeting capability. Furthermore, in vivo mice imaging using MBs-2 for intravenous injection exhibited an obvious and sustained signal increase, which revealed the accumulative of MBs-2 anchoring in tumor. Hence, MBs-2 have been proven to be a promising candidate for using as ultrasound contrast agents for the early diagnosis of αvβ3-overexpressing malignant tumors, including breast cancer.


PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149075 ◽  
Author(s):  
Qiao Hu ◽  
Xiao-Yan Wang ◽  
Li-Ke Kang ◽  
Hai-Ming Wei ◽  
Chun-Mei Xu ◽  
...  

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.


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

2006 ◽  
Vol 32 (10) ◽  
pp. 1473-1478 ◽  
Author(s):  
Grigorios Korosoglou ◽  
Silke Behrens ◽  
Raffi Bekeredjian ◽  
Stefan Hardt ◽  
Marco Hagenmueller ◽  
...  

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