Efficient exosome delivery in refractory tissues assisted by ultrasound-targeted microbubble destruction
Efficient exosome delivery in refractory tissues assisted by ultrasound-targeted microbubble destruction
复制标题
超声靶向微泡破坏辅助外泌体在难治性组织中的有效递送
DOI：
10.1080/10717544.2018.1534898
复制
发表时间：
2019-01-01
期刊：
影响因子：
6
通讯作者：
Yuan, Lijun
中科院分区：
文献类型：
--
作者：
Sun, Wenqi;Li, Zhelong;Yuan, Lijun
摘要近年来，外切体被认为是一种很有前途的药物载体，而某些组织对外切体具有内在的抵抗力。从治疗的角度提高这些组织/器官的药物传递效率，必将拓宽外切体在未来的潜在应用。超声靶向微泡破坏(UTMD)是一种很有前途的非侵入性、靶向给药技术。在这项研究中，我们探索了UTMD在这些内在耐药组织中协助外切体输送的可能性。小鼠接受尾静脉注射dir标记的外切体，并结合/不结合SonoVueTM的UTMD，随后对外切体进行体内和体外追踪。正如预期的那样，心脏、脂肪组织和骨骼肌被发现不愿来自不同来源的外切体。荧光成像和激光共聚焦扫描显微镜(CLSM)显示，靶向破坏心脏和脂肪组织区域的超声微泡(SonoVueTM)显著增加了那里的外体渗透和内吞作用。注射外切体前1 h的UTMD处理不能促进靶区外切体的内吞作用，提示UTMD的瞬时促进作用。此外，UTMD的增加(多次脉冲)并不能线性地增强外切体的输送。总之，我们的研究建立了一种新的策略，通过结合超声微泡和外切体在药物传递中的优势，在不情愿的组织中靶向传递外切体。
Abstract Recently, exosomes have been emerged as promising drug delivery carriers, while certain tissues are intrinsically resistant to exosomes. Therapeutically improving the drug delivery efficiency in these tissues/organs would certainly broaden the potential application of exosomes in future. Ultrasound-targeted microbubble destruction (UTMD) is a promising technique for non-invasive, targeted drug delivery. In this study, we explore the possibility that UTMD assists exosome delivery in these intrinsically resistant tissues. Mice were subjected to tail vein injection of DiR-labeled exosomes together with/without UTMD of SonoVueTM, followed by in vivo and ex vivo tracking of the exosomes. As expected, heart, adipose tissue, and skeletal muscle were found reluctant to exosomes from different origins. Targeted destruction of the ultrasound microbubbles (SonoVueTM) in the heart and adipose tissue region significantly increased the exosome infiltration and endocytosis there, as revealed by fluorescence imaging and confocal laser scanning microscope (CLSM). UTMD treatment 1 h prior to exosome injection failed to facilitate the exosome endocytosis in the targeted region, indicating that the transient promoting effects of UTMD. Moreover, increases of UTMD (numerous pulses) did not linearly enhance the exosome delivery. Together, our study here has established a novel strategy for targeted delivery of exosomes in the reluctant tissues, by combining the advantages of ultrasound microbubbles and exosomes in drug delivery.