Targeted delivery of microRNA-126 to vascular endothelial cells via REDV peptide modified PEG-trimethyl chitosan
Targeted delivery of microRNA-126 to vascular endothelial cells via REDV peptide modified PEG-trimethyl chitosan
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通过REDV肽修饰的PEG-三甲基壳聚糖将microRNA-126靶向递送至血管内皮细胞
DOI：
10.1039/c5bm00629e
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发表时间：
2016
影响因子：
6.6
通讯作者：
Yuan Xiaoyan
中科院分区：
文献类型：
--
作者：
Zhou Fang;Jia Xiaoling;Yang Qingmao;Yang Yang;Zhao Yunhui;Fan Yubo;Yuan Xiaoyan
通过microRNAs （miRNAs）操纵基因表达是治疗心血管和癌症疾病的新兴策略之一。然而，mirna向特定维管组织的有效递送是有限的。在这项工作中，短肽Arg-Glu-Asp-Val （REDV）通过双功能聚乙二醇（PEG）连接物与三甲基壳聚糖（TMC）连接，用于靶向递送microRNA-126 （miRNA-126）到血管内皮细胞（VECs）。研究了TMC/miRNA、TMC-g- peg /miRNA和TMC-g- peg - redv /miRNA复合物的形态、血清稳定性和细胞毒性，以及细胞摄取、增殖和体外miRNA转染效率。通过REDV修饰，与TMC/miRNA和TMC-g- peg /miRNA复合物相比，TMC-g- peg -REDV/miRNA复合物的细胞毒性可以忽略，miRNA-126的表达增加，VEC增殖增强。特别是，miRNA递送和靶向肽REDV修饰所采用的方法促进了血管平滑肌细胞对VECs的选择性摄取和生长。提示REDV肽修饰的TMC-g-PEG复合体有潜力作为miRNA载体应用于人工血管快速内皮化。
Manipulation of gene expression by means of microRNAs (miRNAs) is one of the emerging strategies to treat cardiovascular and cancer diseases. Nevertheless, efficient delivery of miRNAs to a specific vascular tissue is limited. In this work, a short peptide Arg-Glu-Asp-Val (REDV) was linked to trimethyl chitosan (TMC) via a bifunctional poly(ethylene glycol) (PEG) linker for the targeted delivery of microRNA-126 (miRNA-126) to vascular endothelial cells (VECs). The morphology, serum stability and cytotoxicity of the polyplex/miRNA complexes, namely, TMC/miRNA, TMC-g-PEG/miRNA and TMC-g-PEG-REDV/miRNA, were investigated along with the cellular uptake, proliferation and in vitro miRNA transfection efficiency. By REDV modification, the TMC-g-PEG-REDV/miRNA complex showed negligible cytotoxicity, increased expression of miRNA-126 and enhanced VEC proliferation compared with the TMC/miRNA and TMC-g-PEG/miRNA complexes. In particular, the approaches adopted for the miRNA delivery and targeted peptide REDV modification promote the selective uptake and the growth of VECs over vascular smooth muscle cells. It was suggested that the REDV peptide-modified TMC-g-PEG polyplex could be potentially used as a miRNA carrier in artificial blood vessels for rapid endothelialization.