title: A novel peptide for efficient siRNA delivery in vitro and therapeutics in vivo.
abstract: 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.
authors: Department of Chemical Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, ON N2L 3G1, Canada.
authors: Ran
authors: R
authors: Pan
authors: Department of Chemical Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, ON N2L 3G1, Canada.
authors: Wen
authors: W
authors: Xu
authors: Department of Pharmacy, Shanghai 3rd People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201999, China.
authors: Feng
authors: F
authors: Yuan
authors: Department of Chemical Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, ON N2L 3G1, Canada.
authors: Dafeng
authors: D
authors: Chu
authors: Department of Chemical Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, ON N2L 3G1, Canada.
authors: Yong
authors: Y
authors: Ding
authors: Department of Chemical Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, ON N2L 3G1, Canada.
authors: Baoling
authors: B
authors: Chen
authors: Department of Chemical Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, ON N2L 3G1, Canada.
authors: Mousa
authors: M
authors: Jafari
authors: Department of Pharmacy, Shanghai 3rd People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201999, China.
authors: Yongfang
authors: Y
authors: Yuan
authors: Department of Chemical Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, ON N2L 3G1, Canada. Electronic address: p4chen@uwaterloo.ca.
authors: P
authors: P
authors: Chen
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D018625:Microscopy, Atomic Force; D010455:Peptides / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D010455:Peptides; D034741:RNA, Small Interfering
keywords: Cell penetrating peptide; Intratumoral injection; Nuclear localization sequence; Stearic acid; siRNA delivery