Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound
Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound
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DOI：
10.1016/j.jconrel.2013.03.017
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发表时间：
2013-07-10
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;Rifai, Bassel;Coussios, Constantin C.
溶瘤病毒（OV）和超声增强药物递送是强大的新技术。OV选择性地自我扩增并杀死癌细胞，但其临床应用受到从血流到肿瘤的有限递送的限制。超声先前已被用于体内OV的靶向释放，但其用于诱导空化、微泡振荡以增强OV肿瘤外渗和递送的用途先前尚未报道。通过识别和优化潜在的物理机制，这项工作表明，聚焦超声显着增强了全身给药的OV与微泡共注射的输送和生物分布。肿瘤转基因表达增加了50倍，而没有任何可观察到的组织损伤。超声暴露参数作为肿瘤再灌注时间的函数进行了优化，以在整个暴露过程中维持惯性空化（一种微泡活性）。在治疗过程中被动检测声发射证实了惯性空化是增强递送的机制，并能够实时监测成功的病毒递送。(C)2013爱思唯尔有限公司版权所有。基因递送
Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. (C) 2013 Elsevier B.V. All rights reserved. GENE DELIVERY