Design and evaluation of a stearylated multicomponent peptide-siRNA nanocomplex for efficient cellular siRNA delivery.

Wan, Yu, Moyle, Peter M., Gn, Pei Z. and Toth, Istvan (2017) Design and evaluation of a stearylated multicomponent peptide-siRNA nanocomplex for efficient cellular siRNA delivery.. Nanomedicine, 12 4: 281-293. doi:10.2217/nnm-2016-0354


Author Wan, Yu
Moyle, Peter M.
Gn, Pei Z.
Toth, Istvan
Title Design and evaluation of a stearylated multicomponent peptide-siRNA nanocomplex for efficient cellular siRNA delivery.
Journal name Nanomedicine   Check publisher's open access policy
ISSN 1743-5889
1748-6963
Publication date 2017-01-17
Year available 2017
Sub-type Article (original research)
DOI 10.2217/nnm-2016-0354
Open Access Status Not yet assessed
Volume 12
Issue 4
Start page 281
End page 293
Total pages 13
Place of publication London, United Kingdom
Publisher Future Medicine
Language eng
Subject 1502 Bioengineering
2701 Medicine (miscellaneous)
2204 Biomedical Engineering
2500 Materials Science
Abstract Aim: To develop a new synthetic peptide-based nanoparticulate siRNA delivery system. Materials & methods: DEN-K(GALA)-TAT-K(STR) was generated by incorporating stearic acid into a multicomponent peptide (DEN-K(GALA)-TAT), containing a cationic poly-L-lysine dendron, an endosome-disrupting peptide GALA and a cell-penetrating peptide TAT(48-60). Its physicochemical characteristics, size, toxicity, cellular uptake and gene knockdown activity of the peptide/siRNA complexes were studied. Results: DEN-K(GALA)-TAT-K(STR) exhibited a pH-responsive behavior, which assists with endosomal escape. When siRNA was delivered by DEN-K(GALA)-TAT-K(STR), it showed a significantly enhanced cellular uptake, compared with the nonlipidic peptide. This system also displayed enhanced knockdown efficiency and reduced cytotoxicity over the widely used delivery system branched 25-kDa polyethyleneimine. Conclusion: Our stearylated multicomponent delivery system has great potential as an efficient siRNA delivery vector.
Formatted abstract
Aim: To develop a new synthetic peptide-based nanoparticulate siRNA delivery system. Materials & methods: DEN-K(GALA)-TAT-K(STR) was generated by incorporating stearic acid into a multicomponent peptide (DEN-K(GALA)-TAT), containing a cationic poly-L-lysine dendron, an endosome-disrupting peptide GALA and a cell-penetrating peptide TAT(48–60). Its physicochemical characteristics, size, toxicity, cellular uptake and gene knockdown activity of the peptide/siRNA complexes were studied. Results: DEN-K(GALA)-TAT-K(STR) exhibited a pH-responsive behavior, which assists with endosomal escape. When siRNA was delivered by DEN-K(GALA)-TAT-K(STR), it showed a significantly enhanced cellular uptake, compared with the nonlipidic peptide. This system also displayed enhanced knockdown efficiency and reduced cytotoxicity over the widely used delivery system branched 25-kDa polyethyleneimine. Conclusion: Our stearylated multicomponent delivery system has great potential as an efficient siRNA delivery vector.
Keyword Cell-penetrating peptide
siRNA delivery
Poly-L-lysine
Nonviral vectors
Lipidic peptide
Endosome-disrupting peptide
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DP130100952
569869
DP110100212
Institutional Status UQ

 
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Created: Fri, 20 Jan 2017, 22:25:03 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences