A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier.
A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier.
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DOI：
10.1038/s41598-023-50203-3
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发表时间：
2024-01-22
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
血脑屏障（BBB）是药物治疗到达大脑的障碍。随着神经血管疾病和脑癌转移的发病率增加，需要理想的体外模型来开发用于增强药物递送至脑的新方法。在这里，我们建立了一个多细胞人脑球体模型，模仿BBB的结构和功能。在球体内，内皮细胞和周细胞定位于外周，而神经元，星形胶质细胞和小胶质细胞分布在整个。超声靶向微泡空化（UTMC）是一种新型的无创性增强内皮药物渗透性的技术。我们利用我们的三维（3D）模型来研究调节UTMC诱导的高渗透性的可行性和机制。UTMC导致10 kDa德克萨斯红葡聚糖（TRD）渗透到超出BBB 100 µm的球状体中显着增加，而不影响细胞活力。这种高通透性依赖于UTMC诱导的钙（Ca2+）内流和内皮型一氧化氮合酶（eNOS）的激活。我们的3D脑球体模型具有完整和功能性的BBB，为研究UTMC的生物效应提供了一个有价值的平台，包括在空间上远离内皮屏障的效应。
The blood‒brain barrier (BBB) acts as a hindrance to drug therapy reaching the brain. With an increasing incidence of neurovascular diseases and brain cancer metastases, there is a need for an ideal in vitro model to develop novel methodologies for enhancing drug delivery to the brain. Here, we established a multicellular human brain spheroid model that mimics the BBB both architecturally and functionally. Within the spheroids, endothelial cells and pericytes localized to the periphery, while neurons, astrocytes, and microglia were distributed throughout. Ultrasound-targeted microbubble cavitation (UTMC) is a novel noninvasive technology for enhancing endothelial drug permeability. We utilized our three-dimensional (3D) model to study the feasibility and mechanisms regulating UTMC-induced hyperpermeability. UTMC caused a significant increase in the penetration of 10 kDa Texas red dextran (TRD) into the spheroids, 100 µm beyond the BBB, without compromising cell viability. This hyperpermeability was dependent on UTMC-induced calcium (Ca2+) influx and endothelial nitric oxide synthase (eNOS) activation. Our 3D brain spheroid model, with its intact and functional BBB, offers a valuable platform for studying the bioeffects of UTMC, including effects occurring spatially distant from the endothelial barrier.
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影响因子：
2.3
作者：
Zheng W;Benner EM;Bloom DC;Muralidaran V;Caldwell JK;Prabhudesai A;Piazza PA;Wood J;Kinchington PR;Nimgaonkar VL;D'Aiuto L
通讯作者：
D'Aiuto L
影响因子：
4.6
作者：
Chang, William Lim Kee;Chan, Tiffany G.;Raguseo, Federica;Mishra, Aishwarya;Chattenton, Dani;de Rosales, Rafael T. M.;Long, Nicholas J.;Morse, Sophie V.
通讯作者：
Morse, Sophie V.
DOI：
10.1073/pnas.1606915113
发表时间：
2016-09-06
影响因子：
11.1
作者：
Helfield, Brandon;Chen, Xucai;Villanueva, Flordeliza S.
通讯作者：
Villanueva, Flordeliza S.
影响因子：
5.7
作者：
Hynynen, K;McDannold, N;Vykhodtseva, N
通讯作者：
Vykhodtseva, N
影响因子：
5.6
作者：
Costamagna G;Comi GP;Corti S
通讯作者：
Corti S