Synthetic θ-Defensin Antibacterial Peptide as a Highly Efficient Nonviral Vector for Redox-Responsive miRNA Delivery

被引：20

作者：

Yu, Meng ^{[1
]}

Yan, Jin ^{[2
]}

He, Wangxiao ^{[2
]}

Li, Chenyu ^{[3
]}

Ma, Peter X. ^{[4
]}

Lei, Bo ^{[1
]}

机构：

[1] Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an,710054, China

[2] Center for Translational Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an,710049, China

[3] School of Science, Xi'an Jiaotong University, Xi'an,710054, China

[4] Department of Biologic and Materials Sciences, Department of Biomedical Engineering, Macromolecular Science and Engineering Center, Department of Materials Science and Engineering, University of Michigan, Ann Arbor,MI,48109, United States

来源：

Advanced Biosystems | 2017年 / 1卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Genes - Liposomes - RNA - Biocompatibility - Gene transfer - Stem cells - Sulfur compounds - Amino acids - Efficiency - Cell culture - Vectors - Biodegradation;

D O I：

10.1002/adbi.201700001

中图分类号：

学科分类号：

摘要：

Synthetic cationic vectors have shown great promise for nonviral gene delivery. However, their cytotoxicity and low efficiency impose great restrictions on clinic applications. To push through this limitation, humanized peptides or proteins with cationic biocompatibility as well as biodegradation would be an excellent candidate. Herein, for the first time, we describe how an arginine-rich humanized antimicrobial cyclopeptide, θ-defensin, can be used as a synthetic cationic vector to load and deliver miRNA into bone mesenchymal stem cells with high efficiency and ultralow cytotoxicity, surpassing the efficiency of the commercial polyethylenimine (25 kD) and Lipofectamine 3000. To note, θ-defensin can redox-responsively release the loaded miRNA through a structural change: in extracellular oxidative environment, θ-defensin has large β-sheet structures stabilized by three disulfide linkages, and this special structure enables highly efficient delivery of miRNA by passing through cell membranes; in intracellular environment, redox-responsive disulfide linkages are broken and the tight β-sheet structures are destroyed, so that the miRNA can be released. Our results suggest that synthetic θ-defensin peptides are a new class of nonviral gene vectors and this study may also provide a promising strategy to design smart-responsive gene vectors with high efficiency and minimal toxicity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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