体外血脑屏障的构建及金属离子/金属纳米粒子透过性评价

引用本文: 姜泽, 张璇, 刘金辉, 魏星, 陈明丽, 王建华. 体外血脑屏障的构建及金属离子/金属纳米粒子透过性评价[J]. 分析化学, 2021, 49(10): 1657-1665. doi: 10.19756/j.issn.0253-3820.210406 shu

Citation: JIANG Ze, ZHANG Xuan, LIU Jin-Hui, WEI Xing, CHEN Ming-Li, WANG Jian-Hua. Construction of Human Blood-Brain Barrier in Vitro and Permeability Evaluation of Metal Ions or Metal Nanoparticles[J]. Chinese Journal of Analytical Chemistry, 2021, 49(10): 1657-1665. doi: 10.19756/j.issn.0253-3820.210406 shu

体外血脑屏障的构建及金属离子/金属纳米粒子透过性评价

东北大学理学院化学系, 沈阳 110819

通讯作者: 陈明丽,E-mail:chenml@mail.neu.edu.cn; 王建华,E-mail:jianhuajrz@mail.neu.edu.cn

基金项目:
国家自然科学基金项目（Nos.21727811，21922402）、中央高校基本科研业务费专项资金项目（Nos.N2005003，N2105017）、辽宁省兴辽英才计划项目（No.XLYC1802016）和辽宁省高校创新人才支持计划项目（No.ZX20200088）资助。

摘要: 构建了一种人体外血脑屏障微流控芯片用于评估金属和金属纳米粒子的透过性。结合"三明治"血脑屏障模型和集成浓度梯度生成单元芯片，实现了不同浓度下金属相关组份的透过评估。利用bEnd.3细胞构建血脑屏障模型，采用电感耦合等离子体质谱（ICP-MS）法对体外血脑屏障模型中金属离子和金属纳米粒子的跨膜效应和屏障吸收定量检测。通过Comsol模拟软件对芯片浓度梯度生成单元混合效果进行理论模拟，采用罗丹明B溶液和含镉的实际样品评价了其实际混合效果，采用原子吸收光谱评估了其可靠性。屏障渗透性评估实验结果表明，荧光素钠的血脑屏障渗透率为（5.45±0.48）×10^-6 cm/s，与文献报道值基本一致。此芯片能够实现稳定的浓度生成、体外血脑屏障器官的模拟以及其对金属溶液透过性的评估，有望用于中枢神经药物筛选和金属、纳米粒子神经毒性评估等领域。

关键词:

English

Construction of Human Blood-Brain Barrier in Vitro and Permeability Evaluation of Metal Ions or Metal Nanoparticles

Department of Chemistry, College of Science, Northeastern University, Shenyang 110819, China

Corresponding author: CHEN Ming-Li, ; WANG Jian-Hua,

Received Date: 01 April 2021
Revised Date: 16 August 2021
Fund Project:
Supported by the National Natural Science Foundation of China (Nos.21727811, 21922402), the Fundamental Research Funds for the Central Universities (Nos.N2005003, N2105017), the Liaoning Revitalization Talents Program (No.XLYC1802016) and the Innovative Talents Support Program for Universities of Liaoning Province, China (No.ZX20200088).

Abstract: An in vitro blood-brain barrier (BBB) microfluidic chip was constructed to evaluate the transmittance of metal and metal nanoparticles. By combining with the "sandwich" blood-brain barrier model, the concentration gradient generation unit was integrated on the chip to realize permeability evaluation of metal-related components at different concentrations. bEnd.3 cells were employed as BBB model cells, and inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure metal ions and metal nanoparticles trans-membrane and barrier absorption in the model in vitro. The mixing effect of the fluid in the chip channel was theoretically simulated by Comsol simulation software. The actual mixing effect was evaluated with samples including cadmium and Rhodamine B solution, and the reliability of the concentration gradient generation unit of the actual sample was evaluated by atomic absorption spectroscopy. In the barrier permeability evaluation experiment, the BBB permeability of sodium fluorescein was (5.45±0.48)×10^-6 cm/s, which was basically consistent with the previous research. The chip could generate stable concentration generation, realize in vitro simulation of BBB organs and evaluation of metal permeability, which was expected to be used in the future in the central nervous system drug screening and metal, nanoparticle neurotoxicity assessment and other fields.

Key words:

Microfluidics
/ Blood-brain barrier
/ Metal toxicity
/ Inductively coupled plasma-mass spectrometry

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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

体外血脑屏障的构建及金属离子/金属纳米粒子透过性评价

通讯作者: 陈明丽,E-mail:chenml@mail.neu.edu.cn; 王建华,E-mail:jianhuajrz@mail.neu.edu.cn

English

Construction of Human Blood-Brain Barrier in Vitro and Permeability Evaluation of Metal Ions or Metal Nanoparticles

Corresponding author: CHEN Ming-Li, ; WANG Jian-Hua,

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

体外血脑屏障的构建及金属离子/金属纳米粒子透过性评价

通讯作者: 陈明丽,E-mail:chenml@mail.neu.edu.cn; 王建华,E-mail:jianhuajrz@mail.neu.edu.cn

English

Construction of Human Blood-Brain Barrier in Vitro and Permeability Evaluation of Metal Ions or Metal Nanoparticles

Corresponding author: CHEN Ming-Li, ; WANG Jian-Hua,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

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