Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model
Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model
复制标题
DOI：
10.1016/j.jconrel.2011.09.086
复制
发表时间：
2012-01-30
影响因子：
10.8
通讯作者：
Coussios, Constantin-C.
中科院分区：
文献类型：
--
作者：
Bazan-Peregrino, Miriam;Arvanitis, Costas D.;Coussios, Constantin-C.
我们研究了0.5 MHz超声诱导的空化是否可以改善一种有效的乳腺癌选择性溶瘤腺病毒AdEHE 2F-Luc向远离血管的肿瘤区域的外渗和分布。我们开发了一种新型的肿瘤模拟模型，该模型由含有人类乳腺癌细胞的凝胶基质组成，该凝胶基质由模拟肿瘤血管的流体通道穿过，通过该流体通道可以使病毒和微泡流动。选择超声压力以使与惯性空化相关的宽带发射或与稳定空化相关的超谐波发射最大化，同时改变占空比以保持递送的总声能恒定，以进行跨暴露的比较。在不存在腺病毒的情况下，测试的暴露条件均不影响细胞活力。当AdEHE 2F-Luc通过血管输送时，惯性气穴使肿瘤细胞中的转基因表达增加了高达200倍。在不存在科萨基和腺病毒受体细胞表达的情况下未观察到这种增加，不考虑声致穿孔作为作用机制。在存在惯性空化的情况下，AdEHE 2F-Luc在血管周围基质中的分布大大改善，特别是在超声波束的方向上;这使得AdEHE 2F-Luc能够在递送后24小时杀死凝胶中超声聚焦体积内高达80%的癌细胞，而在不存在空化的情况下为0%。(C)2011爱思唯尔有限公司版权所有。
We investigated whether ultrasound-induced cavitation at 0.5 MHz could improve the extravasation and distribution of a potent breast cancer-selective oncolytic adenovirus, AdEHE2F-Luc, to tumour regions that are remote from blood vessels. We developed a novel tumour-mimicking model consisting of a gel matrix containing human breast cancer cells traversed by a fluid channel simulating a tumour blood vessel, through which the virus and microbubbles could be made to flow. Ultrasonic pressures were chosen to maximize either broadband emissions, associated with inertial cavitation, or ultraharmonic emissions, associated with stable cavitation, while varying duty cycle to keep the total acoustic energy delivered constant for comparison across exposures. None of the exposure conditions tested affected cell viability in the absence of the adenovirus. When AdEHE2F-Luc was delivered via the vessel, inertial cavitation increased transgene expression in tumour cells by up to 200 times. This increase was not observed in the absence of Coxsackie and Adenovirus Receptor cell expression, discounting sonoporation as the mechanism of action. In the presence of inertial cavitation, AdEHE2F-Luc distribution was greatly improved in the matrix surrounding the vessel, particularly in the direction of the ultrasound beam; this enabled AdEHE2F-Luc to kill up to 80% of cancer cells within the ultrasound focal volume in the gel 24 hours after delivery, compared to 0% in the absence of cavitation. (C) 2011 Elsevier B.V. All rights reserved.