DEVELOPMENT OF LOCALIZED GENE DELIVERY USING A DUAL-INTENSITY ULTRASOUND SYSTEM IN THE BLADDER
DEVELOPMENT OF LOCALIZED GENE DELIVERY USING A DUAL-INTENSITY ULTRASOUND SYSTEM IN THE BLADDER
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DOI：
10.1016/j.ultrasmedbio.2010.07.015
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发表时间：
2010-11-01
影响因子：
2.9
通讯作者：
Kodama, Tetsuya
中科院分区：
文献类型：
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作者：
Horie, Sachiko;Watanabe, Yukiko;Kodama, Tetsuya
使用纳米气泡的双强度超声系统(DIUS)为局部基因传递提供了机会。该系统由低/高超声强度组成。膀胱是一个气球形状的封闭器官，在其中纳米气泡的行为可以通过超声波照射在空间和时间上进行控制。我们假设，当使用带有纳米气泡的DIUS时，低强度的超声波会将纳米气泡引导到膀胱中的目标细胞，而高强度的超声波会使纳米气泡破裂，增加细胞膜的通透性，从而促进外源分子进入邻近细胞。一种高频超声成像系统表征了膀胱中纳米气泡的运动和破碎。共聚焦显微镜显示荧光分子在局部的膀胱壁中传递，而组织化学检查表明分子转移效率依赖于声能。生物发光成像系统显示，荧光素酶的DNA实际上是在膀胱壁中转移的，随后的转移依赖于声能。这些发现表明，使用这种方法在膀胱内传递外源分子会导致分子传递的高度局部化，从而促进膀胱癌的基因治疗。(电子邮件：KoDama@bme.tohoku.ac.jp)(C)2010年世界医学和生物学超声联合会。
A dual-intensity ultrasound system (DIUS) using nanobubbles offers opportunities for localized gene delivery. This system consists of low-/high-ultrasound intensities. The bladder is a balloon-shaped closed organ in which the behavior of nanobubbles can be controlled spatially and temporally by ultrasound exposure. We hypothesized that when a DIUS with nanobubbles was used, low-intensity ultrasound would direct nanobubbles to targeted cells in the bladder, whereas high-intensity ultrasound intensity would collapse nanobubbles and increase cell membrane permeability, facilitating entry of exogenous molecules into proximate cells. A high-frequency ultrasound imaging system characterized movement and fragmentation of nanobubbles in the bladder. Confocal microscopy revealed that fluorescent molecules were delivered in the localized bladder wall, whereas histochemical examination indicated that the molecular transfer efficiency depended on the acoustic energy. A bioluminescence imaging system showed luciferase plasmid DNA was actually transfected in the bladder wall and subsequent transfection depended on acoustic energy. These findings indicate that delivery of exogenous molecules in the bladder using this approach results in high localization of molecular delivery, facilitating gene therapy for bladder cancer. (E-mail: kodama@bme.tohoku.ac.jp) (C) 2010 World Federation for Ultrasound in Medicine & Biology.