Investigating the optimum size of nanoparticles for their delivery into the brain assisted by focused ultrasound-induced blood-brain barrier opening.
Investigating the optimum size of nanoparticles for their delivery into the brain assisted by focused ultrasound-induced blood-brain barrier opening.
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研究了纳米颗粒的最佳尺寸，以通过聚焦超声引起的血脑屏障开口辅助进入大脑。
DOI：
10.1038/s41598-020-75253-9
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发表时间：
2020-10-26
影响因子：
4.6
通讯作者：
Ito T
中科院分区：
文献类型：
--
作者：
Ohta S;Kikuchi E;Ishijima A;Azuma T;Sakuma I;Ito T
血脑屏障（BBB）阻碍了通过常规策略将纳米颗粒递送到脑中的效率。通过聚焦超声（FUS）扩大BBB紧密连接提供了一种有前途的方法，用于增强纳米颗粒向大脑中的递送。然而，目前对纳米颗粒如何通过开放的BBB间隙的理解不足。在这里，我们研究了通过FUS诱导的BBB开放辅助的纳米颗粒递送到大脑中的尺寸依赖性，使用直径为3，15和120 nm的金纳米颗粒（AuNPs）。对于3-和15-nm的金纳米颗粒，FUS暴露显著增加了通过体外BBB模型的渗透高达9.5倍，并且直径越小，渗透性越高。然而，小鼠体内经颅FUS暴露表明，较小的颗粒不一定更适合递送到大脑中。与3-和120-nm颗粒相比，中等尺寸（15 nm）的AuNPs显示出最高的递送效率（0.22%ID）。一个计算模型表明，这个最佳的大小是由它们通过开放的血脑屏障间隙的渗透和它们从血液中的排泄之间的竞争。我们的研究结果将大大有助于设计纳米粒子，将其输送到大脑中治疗中枢神经系统疾病。
The blood–brain barrier (BBB) has hampered the efficiency of nanoparticle delivery into the brain via conventional strategies. The widening of BBB tight junctions via focused ultrasound (FUS) offers a promising approach for enhancing the delivery of nanoparticles into the brain. However, there is currently an insufficient understanding of how nanoparticles pass through the opened BBB gaps. Here we investigated the size-dependence of nanoparticle delivery into the brain assisted by FUS-induced BBB opening, using gold nanoparticles (AuNPs) of 3, 15, and 120 nm diameter. For 3- and 15-nm AuNPs, FUS exposure significantly increased permeation across an in vitro BBB model by up to 9.5 times, and the permeability was higher with smaller diameter. However, in vivo transcranial FUS exposure in mice demonstrated that smaller particles were not necessarily better for delivery into the brain. Medium-sized (15 nm) AuNPs showed the highest delivery efficiency (0.22% ID), compared with 3- and 120-nm particles. A computational model suggested that this optimum size was determined by the competition between their permeation through opened BBB gaps and their excretion from blood. Our results would greatly contribute to designing nanoparticles for their delivery into the brain for the treatment of central nervous system diseases.
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影响因子：
2.9
作者：
Choi, James J.;Wang, Shougang;Tung, Yao-Sheng;Morrison, Barclay, III;Konofagou, Elisa E.
通讯作者：
Konofagou, Elisa E.
影响因子：
16.6
作者：
Anraku Y;Kuwahara H;Fukusato Y;Mizoguchi A;Ishii T;Nitta K;Matsumoto Y;Toh K;Miyata K;Uchida S;Nishina K;Osada K;Itaka K;Nishiyama N;Mizusawa H;Yamasoba T;Yokota T;Kataoka K
通讯作者：
Kataoka K
影响因子：
3.5
作者：
McDannold, N;Vykhodtseva, N;Hynynen, K
通讯作者：
Hynynen, K
DOI：
10.1073/pnas.0604318103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Kinoshita, Manabu;McDannold, Nathan;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo
DOI：
10.1016/j.jconrel.2013.04.007
发表时间：
2013-07-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Aryal M;Vykhodtseva N;Zhang YZ;Park J;McDannold N
通讯作者：
McDannold N