Experimental study on enhancement effect and targeting study in vitro of VEGFR-3-targetedlipid microbubble ultrasound contrast agents containing adriamycin

YE Ming; WANG Zhi-gang; ZHOU Hong; NIU Cheng-cheng; CHEN Chang-yu; LIU Ying

Journal of China Clinic Medical Imaging ›› 2015, Vol. 26 ›› Issue (7) : 509-511.

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Experimental study on enhancement effect and targeting study in vitro of VEGFR-3-targetedlipid microbubble ultrasound contrast agents containing adriamycin

YE Ming1, WANG Zhi-gang2, ZHOU Hong1, NIU Cheng-cheng3, CHEN Chang-yu1, LIU Ying1

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Abstract

Objective: To prepare VEGFR-3-targeted lipid microbubble ultrasound contrast agents containing adriamycin, and investigate their enhancement effect and affinity on human lymphatic endothelial cells in vitro. Methods: The biotinylated degree of prepared biotinylated monoclonal antibody VEGFR-3 was determined. The microbubbles containing adriamycin were prepared by mechanical vibration. Then the biotinylated antibody was attached to the surface of the microbubbles by avidin-biotin interaction. The physical property was determined and the enhancement effect in vitro was observed with ultrasound, The conjugation of targeted lipid microbubble ultrasound contrast agents containing adriamycin with human lymphatic endothelial cells was proved by light microscope and fluorescence microscope, with non-targeted microbubbles served as control group. Results: About 9 biotin molecules were coupled to each antibody in average. The disposition of the prepared microbubbles was uniform size, the mean diameter was 1.66 μm. In vitro, the prepared microbubbles showed hyperechogenicity in US imaging. In the targeting study in vitro, it was shown that the conjugation of the targeted microbubbles containing adriamycin with human lymphatic endothelial cells was tight while control group was negative. Conclusions: VEGFR-3-targeted lipid ultrasound microbubbles contrast agents containing adriamycin are successfully prepared, with higher entrapment efficiency and drug-loading amounts, which have strong enhancement effect and targeting function in vitro.

Key words

Endothelial cells / Vascular endothelial growth factor receptor-3 / Lymphatic vessels / Contrast media

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YE Ming;WANG Zhi-gang;ZHOU Hong;NIU Cheng-cheng;CHEN Chang-yu;LIU Ying. Experimental study on enhancement effect and targeting study in vitro of VEGFR-3-targetedlipid microbubble ultrasound contrast agents containing adriamycin[J]. Journal of China Clinic Medical Imaging. 2015, 26(7): 509-511