PEGylated PLGA-based phase shift nanodroplets combined with focused ultrasound for blood brain barrier opening in rats.
PEGylated PLGA-based phase shift nanodroplets combined with focused ultrasound for blood brain barrier opening in rats.
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基于聚乙二醇化 PLGA 的相移纳米液滴结合聚焦超声用于大鼠血脑屏障开放
DOI：
10.18632/oncotarget.17155
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发表时间：
2017-06-13
期刊：
影响因子：
--
通讯作者：
Cheng Y
中科院分区：
文献类型：
--
作者：
Zhang X;Hu J;Zhao G;Huang N;Tan Y;Pi L;Huang Q;Wang F;Wang Z;Wang Z;Cheng Y
以往的研究表明，聚焦超声(FUS)联合全身注射微泡(MBS)可以局部、瞬时和可逆地开放血脑屏障(BBB)。然而，由于MBS的直径很小，MBS被限制在血管内空间，不能通过开放的BBB渗入病变部位。在本研究中，我们制备了一种由液态全氟戊烷核和聚乙二醇聚(丙交酯-乙醇酸)壳组成的纳米级液滴。在FUS作用下，纳米液滴具有实现液-气相变的能力。当声压达到1.0 Mpa时，出现明显的伊文氏蓝渗出。当压力增加到1.5 Mpa时，可观察到脑内出血和红细胞渗出。延长超声时间可提高血脑屏障开放程度，同时加宽时间窗。此外，与MBS相比，EB渗出的分布牢牢地局限在病灶中心的狭窄区域内，提示FUS可较高精度地控制BBB开口的部位。结果表明，聚乙二醇化的PLGA相移纳米液滴作为FUS诱导血脑屏障开放的有效介体是可行的。
Previous studies have shown that focused ultrasound (FUS) combined with systematic administration of microbubbles (MBs) can open the blood brain barrier (BBB) locally, transiently and reversibly. However, because of the micro size diameters, MBs are restricted in the intravascular space and cannot extravasate into diseased sites through the opened BBB. In this study, we fabricated one kind of nanoscale droplets which consisted of encapsulated liquid perfluoropentane cores and poly (ethyleneglycol) - poly (lactide-co-glycolic acid) shells. The nanodroplets had the capacity to realize liquid to gas phase shift under FUS. Significant extravasation of Evan's blue appeared when acoustic pressure reached 1.0 MPa. Intracerebral hemorrhages and erythrocyte extravasations were observed when the pressure was increased to 1.5 MPa. Prolonged sonication duration could enhance the level of BBB opening and broaden the time window simultaneously. Furthermore, compared with MBs, the distribution of EB extravasation was firmly confined within narrow region in the center of focal zone, suggesting the site of FUS induced BBB opening could be controlled with high precision by this procedure. Our results show the feasibility of serving PEGylated PLGA-based phase shift nanodroplet as an effective alternative mediating agent for FUS induced BBB opening.
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影响因子：
10.2
作者：
Mahapatro A;Singh DK
通讯作者：
Singh DK
影响因子：
10.8
作者：
Airan RD;Meyer RA;Ellens NP;Rhodes KR;Farahani K;Pomper MG;Kadam SD;Green JJ
通讯作者：
Green JJ
影响因子：
10.8
作者：
Fonseca, C;Simoes, S;Gaspar, R
通讯作者：
Gaspar, R
DOI：
10.1186/s40349-016-0049-8
发表时间：
2016
期刊：
Journal of therapeutic ultrasound
影响因子：
--
作者：
Gallay MN;Moser D;Rossi F;Pourtehrani P;Magara AE;Kowalski M;Arnold A;Jeanmonod D
通讯作者：
Jeanmonod D
影响因子：
14
作者：
Fan, Ching-Hsiang;Chang, En-Ling;Yeh, Chih-Kuang
通讯作者：
Yeh, Chih-Kuang