中国神经再生研究(英文版)

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

非病毒脂质体载体转导脑源性神经营养因子可靶向透过血脑屏障

  

  • 收稿日期:2016-02-15 出版日期:2016-04-30 发布日期:2016-04-30
  • 基金资助:

    吉林省发展和改革委员会基金(JF2012C008-3);中国产业创新专项基金项目(JF2016C050-2);吉林大学和吉林友邦制药有限公司联合项目(2015YX323)

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

Ying Xing1, Chun-yan Wen1, Song-tao Li1, Zong-xin Xia1, 2, *   

  1. 1 China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
    2 Central Hospital of Baishan City, Baishan, Jilin Province, China
  • Received:2016-02-15 Online:2016-04-30 Published:2016-04-30
  • Contact: Zong-xin Xia, 2805777060@qq.com, xiazx86@163.com.
  • Supported by:

    This work was funded by a grant from Jilin Province Development and Reform Commission of China, No. JF2012C008-3, Jilin Province Industrial Innovation Special Fund Project of China, No. JF2016C050-2, and the Joint Project between Jilin University and Jilin You-bang Pharmaceutical Co. Ltd., No. 2015YX323.

摘要:

脑源性神经营养因子在中枢神经系统损伤修复中起重要作用,但其不能直接透过血脑屏障,而脂质体作为一种新型非病毒载体,能转运大分子物质跨血脑屏障进入脑内。为此,实验采用脂质体包埋脑源性神经营养因子并进行适当修饰,在成功合成非病毒脂质体Tf-pCMV-BDNF-PEG的基础上,连接具有中枢靶向作用的pGFAP,构建了靶向性更特异的脂质体Tf-pGFAP-BDNF-PEG,并将两种脂质体通过尾静脉注射于大鼠体内发现,此两种脂质体均可以有效透过血脑屏障,且均主要分布于大脑皮质区。Tf-pGFAP-BDNF-PEG在大脑皮质的表达明显高于Tf-pCMV-BDNF-PEG。实验成功构建非病毒靶向脂质体Tf-pGFAP-BDNF-PEG,可通过血脑屏障分布于大脑皮质中,为实现脑源性神经营养因子的脑内靶向治疗提供实验依据。

orcid: 0000-0001-8286-7238 (Zong-xin Xia)

关键词: 神经再生, 脑损伤, 脑源性神经营养因子, 脂质体, 靶向, 载体, 转染, 海马, 皮质, 包封率, 血脑屏障, 转铁蛋白, 胶质纤维酸性蛋白, 聚乙二醇

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.

Key words: nerve regeneration, brain injury, brain-derived neurotrophic factor, liposomes, targeting, vector, transfection, hippocampus, cortex, encapsulation efficiency, blood-brain barrier, transferrin, glial fibrillary acidic protein, polyethylene glycol, neural regeneration