Amphiphilic Peptides for Efficient siRNA Delivery

Authors

Saghar Mozaffari, Chapman UniversityFollow
Emira Bousoik, Chapman UniversityFollow
Farideh Amirrad, Chapman UniversityFollow
Robert Lamboy, Chapman UniversityFollow
Melissa Coyle, Chapman UniversityFollow
Ryley Hall, Chapman UniversityFollow
Abdulaziz Alasmari, Chapman UniversityFollow
Parvin Mahdipoor, Chapman UniversityFollow
Keykavous Parang, Chapman UniversityFollow
Hamidreza Montazeri Aliabadi, Chapman UniversityFollow

Document Type

Article

Publication Date

4-17-2019

Abstract

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 with lipid DOPE significantly enhanced the efficiency of siRNA delivery by up to ~2-fold compared to peptide alone. Based on the data indicating the efficiency of [WR]5 in siRNA delivery, peptides containing arginine residues on the ring and tryptophan residues on the side chain, [R6K]W6 and [R5K]W5, were also evaluated, and demonstrated improved delivery of siRNA. The presence of DOPE again enhanced the siRNA delivery in most cases. [WR]5, [R5K]W5, and [R6K]W6 did not show any significant toxicity in MDA-MB-231, MDA-MB-468, and AU565 WT cells at N/P ratios of 20:1 or less, in the presence and absence of DOPE. Silencing of kinesin spindle protein (KSP) and Janus kinase 2 (JAK2) was evaluated in MDA-MB-231 cells in the presence of the peptides. The addition of DOPE significantly enhanced the silencing efficiency for all selected peptides. In conclusion, peptides containing typtophan and arginine residues were found to enhance siRNA delivery and to generate silencing of targeted proteins in the presence of DOPE.

Comments

This article was originally published in Polymers, volume 11, in 2019. DOI: 10.3390/polym11040703

Recommended Citation

Mozaffari S, Bousoik E, Amirrad F, et al. Amphiphilic peptides for efficient siRNA delivery. Polymers. 2019;11:703. doi: 10.3390/polym11040703

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This work is licensed under a Creative Commons Attribution 4.0 License.