Brain-targeted co-delivery of therapeutic gene and peptide by multifunctional nanoparticles in Alzheimer's disease mice
Brain-targeted co-delivery of therapeutic gene and peptide by multifunctional nanoparticles in Alzheimer's disease mice
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DOI：
10.1016/j.biomaterials.2015.11.060
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发表时间：
2016-02-01
期刊：
影响因子：
14
通讯作者：
Jiang, Chen
中科院分区：
文献类型：
--
作者：
Liu, Yang;An, Sai;Jiang, Chen
多功能纳米载体在调节多种病理功能障碍和克服药物传递障碍的疾病治疗中越来越有前景。在这里，我们开发了一种用于阿尔茨海默病（AD）治疗的多功能纳米载体，通过全身给药，实现基于聚乙二醇化树突聚l -赖氨酸（DGLs）的治疗性基因和肽共递送到大脑。dgl的树状富胺结构为载药提供了丰富的反应位点和正电荷。通过脑靶向配体修饰成功地克服血脑屏障的药物共递送在体外和体内都得到了证明。在转基因AD小鼠中验证了该系统在多次给药后的药效学研究。通过传递非编码RNA质粒，实现了淀粉样蛋白形成关键酶的下调。同时将治疗肽输送到脑内可减少神经原纤维缠结。同时，还观察到AD小鼠的记忆丧失恢复。综上所述，多功能纳米载体为脑部疾病提供了一个良好的药物共给药平台。(C) 2015 Elsevier Ltd.版权所有。
Multifunctional nanocarriers are increasingly promising for disease treatment aimed to regulate multiple pathological dysfunctions and overcome barriers in drug delivery. Here we develop a multifunctional nanocarrier for Alzheimer's disease (AD) treatment by achieving therapeutic gene and peptide co-delivery to brain based on PEGylated dendrigraft poly-L-lysines (DGLs) via systemic administration. The dendritic amine-rich structure of DGLs provides plenty reaction sites and positive charge for drug loading. Successful co-delivery of drugs overcoming the blood brain barrier by brain-targeted ligand modification was demonstrated both in vitro and in vivo. The pharmacodynamics study of the system following multiple-dosing treatment was verified in transgenic AD mice. Down-regulation of the key enzyme in amyloid-beta formation was achieved by delivering non-coding RNA plasmid. Simultaneous delivery of the therapeutic peptide into brain leads to reduction of neurofibrillary tangles. Meanwhile, memory loss rescue in AD mice was also observed. Taken together, the multifunctional nanocarrier provides an excellent drug co-delivery platform for brain diseases. (C) 2015 Elsevier Ltd. All rights reserved.