Ultrasound targeted microbubble destruction increases capillary permeability in hepatomas
Ultrasound targeted microbubble destruction increases capillary permeability in hepatomas
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DOI：
10.1016/j.ultrasmedbio.2007.05.003
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发表时间：
2007-10-01
影响因子：
2.9
通讯作者：
Kulaksiz, Hasan
中科院分区：
文献类型：
--
作者：
Bekeredjian, Raffi;Kroll, Richard D.;Kulaksiz, Hasan
超声靶向微泡破坏（UTMD）已发展成为一种有前途的工具，器官特异性基因和药物输送。利用局部高浓度的治疗物质和短暂增加的毛细血管通透性，UTMD可用于治疗超声可及肿瘤。本研究的目的是评估UTMD是否可以局部增加大鼠肝癌模型的毛细血管通透性。此外，我们评估了UTMD是否可以将DNA导入此类肿瘤。通过细胞注射在ACI大鼠的两个后肢中诱导皮下Morris肝癌。将18只大鼠分为3组。每只大鼠只有一个肿瘤用超声波治疗。第一组先注射伊文思蓝，再注射UTMD。第二组在伊文思蓝注射后接受磷酸盐缓冲盐水灌注和超声到靶肿瘤。第三组先给予UTMD，再给予伊文思蓝注射。收获肿瘤和对照器官，并定量伊文思蓝外渗。另外12只大鼠通过UTMD接受了负载DNA的微泡，用于治疗一个肿瘤，编码荧光素酶。与对照肿瘤相比，埃文斯蓝注射后进行UTMD显示靶肿瘤中的埃文斯蓝量高约5倍。与此相反，没有显着差异，在伊文思蓝含量检测靶肿瘤和对照组之间的超声时，没有微泡或当UTMD进行之前，伊文思蓝注射。质粒转染不成功。总之，超声靶向微泡破坏能够暂时增加肝癌毛细血管通透性。使用裸DNA，这种技术似乎不适用于肝癌的非侵入性转染。（电子邮件：raffi. med.uni-heidelberg.de）（C）2007年世界医学和生物学超声联合会。
Ultrasound-targeted microbubble destruction (UTMD) has evolved as a promising tool for organ-specific gene and drug delivery. Taking advantage of high local concentrations of therapeutic substances and transiently increased capillary permeability, UTMD could be used for the treatment of ultrasound accessible tumors. The aim of this study was to evaluate if UTMD can locally increase capillary permeability in a hepatoma model of the rat. Furthermore, we evaluated whether UTMD can transfect DNA into such tumors. Subcutaneous Morris hepatomas were induced in both hind limbs of ACI rats by cell injection. A total of 18 rats were divided into three groups. Only one tumor per rat was treated by ultrasound. The first group received injection of Evans blue, followed by UTMD. The second group received a phosphate-buffered saline solution infusion and ultrasound to the target tumor after Evans blue injection. The third group received UTMD first, followed by Evans blue injection. Tumors and control organs were harvested, and Evans blue extravasation was quantified. Another 12 rats received DNA-loaded microbubbles by UTMD to one tumor, encoding for luciferase. Evans blue injection followed by UTMD showed about fivefold higher Evans blue amount in the target tumors compared with the control tumors. In contrast, no significant difference in Evans blue content was detected between target and control tumors when ultrasound was applied without microbubbles or when UTMD was performed before Evans blue injection. Plasmid transfection was not successful. In conclusion, ultrasound targeted microbubble destruction is able to transiently increase capillary permeability in hepatomas. Using naked DNA, this technique does not seem to be feasible for noninvasive transfection of hepatomas. (E-mail: raffi.bekeredjian@med.uni-heidelberg.de) (C) 2007 World Federation for Ultrasound in Medicine & Biology.