Amphiphilic Peptides for Efficient siRNA Delivery

Autor: Melissa Coyle, Abdulaziz Alasmari, Saghar Mozaffari, Ryley Hall, Parvin Mahdipoor, Robert Lamboy, Hamidreza Montazeri Aliabadi, Emira Bousoik, Keykavous Parang, Farideh Amirrad
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Polymers, Vol 11, Iss 4, p 703 (2019)
Polymers
Volume 11
Issue 4
ISSN: 2073-4360
Popis: A number of amphiphilic cyclic peptides&mdash
[FR]4, [WR]5, and [WK]5&mdash
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 tryptophan and arginine residues were found to enhance siRNA delivery and to generate silencing of targeted proteins in the presence of DOPE.
Databáze: OpenAIRE
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