蜂毒肽
血脑屏障
并行传输
体内
生物物理学
细胞生物学
紧密连接
肽
材料科学
膜
生物
神经科学
磁导率
中枢神经系统
生物化学
生物技术
作者
Raleigh M. Linville,Alexander Komin,Xiaoyan Lan,Jackson G. DeStefano,Chengyan Chu,Guanshu Liu,Piotr Walczak,Kalina Hristova,Peter C. Searson
出处
期刊:Biomaterials
[Elsevier]
日期:2021-08-01
卷期号:275: 120942-120942
被引量:24
标识
DOI:10.1016/j.biomaterials.2021.120942
摘要
The blood-brain barrier (BBB) tightly controls entry of molecules and cells into the brain, restricting the delivery of therapeutics. Blood-brain barrier opening (BBBO) utilizes reversible disruption of cell-cell junctions between brain microvascular endothelial cells to enable transient entry into the brain. Here, we demonstrate that melittin, a membrane active peptide present in bee venom, supports transient BBBO. From endothelial and neuronal viability studies, we first identify the accessible concentration range for BBBO. We then use a tissue-engineered model of the human BBB to optimize dosing and elucidate the mechanism of opening. Melittin and other membrane active variants transiently increase paracellular permeability via disruption of cell-cell junctions that result in transient focal leaks. To validate the results from the tissue-engineered model, we then demonstrate that transient BBBO can be reproduced in a mouse model. We identify a minimum clinically effective intra-arterial dose of 3 μM min melittin, which is reversible within one day and neurologically safe. Melittin-induced BBBO represents a novel technology for delivery of therapeutics into the brain.
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