Comparison of the Efficiency of Complexes Based on S4(13)-PV Cell-Penetrating Peptides in Plasmid DNA and siRNA Delivery

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Ana M Cardoso (Author) Other; Sara Trabulo (Author) Other; Ana L Cardoso (Author) Other; Silvia Maia (Author) Other; Paula Gomes (Author) FCUP; Amalia S Jurado (Author) Other; Maria C P Pedroso de Lima (Author) Other

Journal

Title: Molecular Pharmaceutics

Vol. 10

Pages: 2653-2666

ISSN: 1543-8384

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 17 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-006-9MX

DOI: 10.1021/mp400078h

Abstract (EN): The successful application of gene therapy approaches is highly dependent on the efficient delivery of nucleic acids into target cells. In the present study, new peptide-based nonviral systems were developed to enhance plasmid DNA and siRNA delivery, aiming at generating appropriate gene delivery and gene silencing tools for preclinical and clinical application. For this purpose, 0 cell-penetrating peptide derived from the wild-type S4(13)-PV peptide was synthesized through the addition of a five-histidine tail to its N-terminus (H-5-S4(13)-PV), and its ability to mediate gene expression and gene silencing was evaluated and compared to that of the wild-type peptide. The histidine-enriched peptide, H-5-S4(13)-PV, proved to be generally more efficient and less toxic than the wild-type peptide in the delivery of plasmid DNA. In addition, complexes of H-5-S4(13)-PV with siRNAs, but not of S4(13)-PV, were efficiently internalized by cells and presented high knockdown activity (63%). Interestingly, systems containing the S4(13)-PV or the H-5-S4(13)-PV peptide exhibited superior biological activity when compared to those containing the reverse NLS or scrambled peptides, suggesting that both the cell-penetrating; sequence and the NLS of the S4(13)-PV peptide influence the competence Of binary and ternary complexes to accomplish nucleic acid delivery. In order to unravel the cancer therapeutic potential of formulations with the histidine-enriched peptide, their efficiency to mediate silencing of the oncogenic protein survivin was evaluated. As opposed to complexes with the wild-type peptide, H-5-S4(13)-PV complexes showed the ability to promote a high survivin knockdown at the level of both protein (44%) and mRNA (73%), in HT1080 cells.

Language: English

Type (Professor's evaluation): Scientific