Cellular uptake of self-assembled cationic peptide-DNA complexes: Multifunctional role of the enhancer chloroquine

Yang, Shu, Coles, David J., Esposito, Anna, Mitchell, Deanne J., Toth, Istvan and Minchin, Rodney F. (2009) Cellular uptake of self-assembled cationic peptide-DNA complexes: Multifunctional role of the enhancer chloroquine. Journal of controlled release, 135 2: 159-165.


Author Yang, Shu
Coles, David J.
Esposito, Anna
Mitchell, Deanne J.
Toth, Istvan
Minchin, Rodney F.
Title Cellular uptake of self-assembled cationic peptide-DNA complexes: Multifunctional role of the enhancer chloroquine
Journal name Journal of controlled release   Check publisher's open access policy
ISSN 0168-3659
Publication date 2009
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.jconrel.2008.12.015
Volume 135
Issue 2
Start page 159
End page 165
Total pages 7
Editor K. Park
Place of publication Netherlands
Publisher Elsevier BV
Collection year 2010
Language eng
Subject C1
111201 Cancer Cell Biology
970106 Expanding Knowledge in the Biological Sciences
Abstract A small library of carriers consisting of various combinations of the cell penetrating peptide TAT, the SV40 Large T protein nuclear localisation signal (NLS) and a cationic dendrimer of 7 lysine residues (DEN) was synthesised and each member was tested for its ability to deliver exogenous DNA to human HeLa cells. We found that the TAT peptide was essential, but not sufficient for efficient uptake of exogenous DNA. The addition of either NLS or DEN significantly enhanced uptake and expression with the most active carrier consisting of the TAT, NLS and DEN peptides. For those peptides that facilitated DNA uptake, the complexes were targeted to intracellular compartments that required incubation with a fusogenic agent such as chloroquine before gene expression was observed. However, our data suggest that chloroquine did not enhance expression solely by promoting endosomal release since a fusogenic peptide derived from the influenza virus haemagglutinin protein did not improve gene expression. Chloroquine was found to protect DNA from degradation and enhance transcription of DNA bound to the respective carriers. Our results demonstrate that multi-component peptide-based gene carriers can be designed to deliver exogenous DNA. The actions of lysosomotropic agents such as chloroquine reveal the multifactorial properties required for carriers used in non-viral gene delivery.
Keyword Peptide-based carriers
Gene delivery
Cell penetrating peptide
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Tue, 07 Jul 2009, 11:01:56 EST by Shirley Rey on behalf of School of Biomedical Sciences