A novel peptide for efficient siRNA delivery in vitro and therapeutics in vivo

被引：19

作者：

Pan, Ran ^{[1
,2
]}

Xu, Wen ^{[1
,2
]}

Yuan, Feng ^{[3
]}

Chu, Dafeng ^{[1
,2
]}

Ding, Yong ^{[1
,2
]}

Chen, Baoling ^{[1
,2
]}

Jafari, Mousa ^{[1
,2
]}

Yuan, Yongfang ^{[3
]}

Chen, P. ^{[1
,2
]}

机构：

[1] Univ Waterloo, Dept Chem Engn, Waterloo, ON N2L 3G1, Canada

[2] Univ Waterloo, Waterloo Inst Nanotechnol, Waterloo, ON N2L 3G1, Canada

[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 3, Dept Pharm, Shanghai 201999, Peoples R China

来源：

ACTA BIOMATERIALIA | 2015年 / 21卷

基金：

加拿大自然科学与工程研究理事会;

关键词：

siRNA delivery; Cell penetrating peptide; Stearic acid; Nuclear localization sequence; Intratumoral injection; CELL-PENETRATING PEPTIDES; TARGETED RNAI; GENE-TRANSFER; NANOPARTICLES; MECHANISM; INTERFERENCE; OCTAARGININE; ARGININE; APTAMER; VECTOR;

D O I：

10.1016/j.actbio.2015.04.002

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Small interfering RNA (siRNA) shows great therapeutic potential due to its ability to regulate gene expression in a highly selective manner. However, its application has been limited by ineffective cellular uptake of siRNAs. To achieve successful gene-silencing efficiency, a safe and effective delivery vector is generally required. In this study, we designed a series of amphipathic peptides that comprised a variant of a nuclear localization sequence, 0-6 histidine residues and an optional stearic acid group. Among these candidates, STR-HK exhibited good characteristics as a safe and efficient siRNA delivery vector, facilitating efficient siRNA delivery to mammalian cells without causing cytotoxicity. Moreover, the intratumoral injection of STR-HK/siRNA complexes achieved high anti-tumor activity through the downregulation of the Bcl-2 protein in mice, with an inhibition rate of 62.8%. Our data demonstrate that STR-HK is a highly promising siRNA delivery vector for therapeutic applications. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

引用

页码：74 / 84

页数：11

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