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非病毒脂质体介导脑源性神经营养因子穿越血脑屏障的转运

Non-viral liposome-mediated transfer of brain-derived neurotrophic factor across the blood-brain barrier.

作者信息

Xing Ying, Wen Chun-Yan, Li Song-Tao, Xia Zong-Xin

机构信息

China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China.

China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China; Central Hospital of Baishan City, Baishan, Jilin Province, China.

出版信息

Neural Regen Res. 2016 Apr;11(4):617-22. doi: 10.4103/1673-5374.180747.

Abstract

Brain-derived neurotrophic factor (BDNF) plays an important role in the repair of central nervous system injury, but cannot directly traverse the blood-brain barrier. Liposomes are a new type of non-viral vector, able to carry macromolecules across the blood-brain barrier and into the brain. Here, we investigate whether BDNF could be transported across the blood-brain barrier by tail-vein injection of liposomes conjugated to transferrin (Tf) and polyethylene glycol (PEG), and carrying BDNF modified with cytomegalovirus promoter (pCMV) or glial fibrillary acidic protein promoter (pGFAP) (Tf-pCMV-BDNF-PEG and Tf-pGFAP-BDNF-PEG, respectively). Both liposomes were able to traverse the blood-brain barrier, and BDNF was mainly expressed in the cerebral cortex. BDNF expression in the cerebral cortex was higher in the Tf-pGFAP-BDNF-PEG group than in the Tf-pCMV-BDNF-PEG group. This study demonstrates the successful construction of a non-virus targeted liposome, Tf-pGFAP-BDNF-PEG, which crosses the blood-brain barrier and is distributed in the cerebral cortex. Our work provides an experimental basis for BDNF-related targeted drug delivery in the brain.

摘要

脑源性神经营养因子(BDNF)在中枢神经系统损伤修复中起重要作用,但不能直接穿过血脑屏障。脂质体是一种新型非病毒载体,能够携带大分子穿过血脑屏障进入脑内。在此,我们研究通过尾静脉注射与转铁蛋白(Tf)和聚乙二醇(PEG)偶联并携带经巨细胞病毒启动子(pCMV)或胶质纤维酸性蛋白启动子(pGFAP)修饰的BDNF的脂质体(分别为Tf-pCMV-BDNF-PEG和Tf-pGFAP-BDNF-PEG),BDNF是否能够穿过血脑屏障。两种脂质体均能穿过血脑屏障,且BDNF主要在大脑皮层表达。Tf-pGFAP-BDNF-PEG组大脑皮层中的BDNF表达高于Tf-pCMV-BDNF-PEG组。本研究证明成功构建了一种非病毒靶向脂质体Tf-pGFAP-BDNF-PEG,其可穿过血脑屏障并分布于大脑皮层。我们的工作为脑内BDNF相关的靶向药物递送提供了实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee29/4870919/35bf605e7023/NRR-11-617-g003.jpg

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