Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 14, 2006; 12(46): 7508-7513
Published online Dec 14, 2006. doi: 10.3748/wjg.v12.i46.7508
Microbubble-enhanced ultrasound exposure improves gene transfer in vascular endothelial cells
Fang Nie, Hui-Xiong Xu, Qing Tang, Ming-De Lu
Fang Nie, Hui-Xiong Xu, Qing Tang, Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Ming-De Lu, Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: All authors contributed equally to the work.
Supported by grants from the Nationl Natural Scientific Foundation of China, No.30300082, 30470467, and Scientific Foundation Committee of Guangdong Province, China, No. 04009360
Correspondence to: Ming-De Lu, MD, DMSc, Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou 510080, Guangdong Province, China. lumd@21cn.com
Telephone: +86-20-87765183 Fax: +86-20-87765183
Received: August 20, 2006
Revised: October 26, 2006
Accepted: November 3, 2006
Published online: December 14, 2006
Abstract

AIM: To explore the effects of ultrasound exposure combined with microbubble contrast agent (SonoVue) on the permeability of the cellular membrane and on the expression of plasmid DNA encoding enhanced green fluorescent protein (pEGFP) transfer into human umbilical vein endothelial cells (HUVECs).

METHODS: HUVECs with fluorescein isothiocyanate-dextran (FD500) and HUVECs with pEGFP were exposed to continuous wave (1.9 MHz, 80.0 mW/cm2) for 5 min, with or without a SonoVue. The percentage of FD500 taken by the HUVECs and the transient expression rate of pEGFP in the HUVECs were examined by fluorescence microscopy and flow cytometry, respectively.

RESULTS: The percentage of FD500-positive HUVECs in the group of ultrasound exposure combined with SonoVue was significantly higher than that of the group of ultrasound exposure alone (24.0% ± 5.5% vs 66.6% ± 4.1%, P < 0.001). Compared with the group of ultrasound exposure alone, the transfection expression rate of pEGFP in HUVECs was markedly increased with the addition of SonoVue (16.1% ± 1.9% vs 1.5% ± 0.2%, P < 0.001). No statistical significant difference was observed in the HUVECs survival rates between the ultrasound group with and without the addition of SonoVue (94.1% ± 2.3% vs 91.1% ± 4.1%).

CONCLUSION: The cell membrane permeability of HUVECs and the transfection efficiency of pEGFP into HUVECs exposed to ultrasound are significantly increased after addition of an ultrasound contrast agent without obvious damage to the survival of HUVECs. This non-invasive gene transfer method may be a useful tool for clinical gene therapy of hepatic tumors.

Keywords: Microbubble; Ultrasound; Gene transfer; Human umbilical vein endothelial cell; Enhanced green fluorescent protein