Journal
ACTA BIOMATERIALIA
Volume 21, Issue -, Pages 74-84Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2015.04.002
Keywords
siRNA delivery; Cell penetrating peptide; Stearic acid; Nuclear localization sequence; Intratumoral injection
Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC),
- Canadian Foundation for Innovation (CFI)
- Waterloo Institute of Nanotechnology (WIN)
- Canada Research Chairs (CRC) program, Excellent young teachers training fund of Shanghai Third People's Hospital, School of medicine, Shanghai Jiao Tong University [11YYQ01, 11YYQ02]
- Excellent young teachers training fund of Shanghai Municipal Education Commission [jdy11003]
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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.
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