Multifunctional peptide-lipid nanocomplexes for efficient targeted delivery of DNA and siRNA into breast cancer cells

Wan, Yu, Dai, Wei, Nevagi, Reshma J., Toth, Istvan and Moyle, Peter M. (2017) Multifunctional peptide-lipid nanocomplexes for efficient targeted delivery of DNA and siRNA into breast cancer cells. Acta Biomaterialia, 59 257-268. doi:10.1016/j.actbio.2017.06.032


Author Wan, Yu
Dai, Wei
Nevagi, Reshma J.
Toth, Istvan
Moyle, Peter M.
Title Multifunctional peptide-lipid nanocomplexes for efficient targeted delivery of DNA and siRNA into breast cancer cells
Journal name Acta Biomaterialia   Check publisher's open access policy
ISSN 1742-7061
1878-7568
Publication date 2017-06-24
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.actbio.2017.06.032
Open Access Status Not yet assessed
Volume 59
Start page 257
End page 268
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Abstract The development of carriers for the delivery of oligonucleotide therapeutics is essential for the successful translation of gene therapies to the clinic. In the present study, a delivery system, which combines the fusogenic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) with a well-defined synthetic multifunctional peptide, was produced and optimized for gene delivery, with the aim to develop an efficient gene delivery platform for breast cancer cells. For this purpose, a breast cancer-specific cell targeting peptide (CTP) was incorporated into our leading peptide-based gene delivery system (to generate DEN-K(GALA)-TAT-K(STR)-CTP) to improve its cell-specific internalization, and investigated in combination with a formulation approach (DOPE/1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)). DEN-K(GALA)-TAT-K(STR)-CTP alone efficiently complexed with DNA or siRNA, and promoted efficient cellular uptake, but low levels of gene expression. By adding the formulation approach, synergistic improvements in gene expression and silencing were observed compared to the peptide or formulation approaches alone. Of significance, this current system demonstrated more efficient gene knockdown when compared to the leading commercial siRNA delivery agent Lipofectamine® RNAiMAX. The utility of this system was demonstrated through the delivery of BCL2 (B-cell lymphoma 2) siRNA to MCF-7 cells, which led to near complete knockdown of the Bcl-2 protein, and inhibition of MCF-7 cell migration in a wound healing assay. The present peptide/lipid hybrid system is an excellent candidate for the delivery of DNA or siRNA into breast cancer cells.
Keyword Non-viral Vectors
Peptide
RNA interference
Breast cancer
Gene therapy
Bcl2
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Mon, 03 Jul 2017, 09:47:45 EST by Peter Moyle on behalf of School of Pharmacy