Self-assembly of Peptide Amphiphiles with Alkyl Groups for siRNA Delivery

Abstract

Based on the self-assembling amphiphilic peptide GAVILRR, we developed a peptide amphiphile bearing octanoyl and octaarginine groups that formed stable nanoparticles with siRNA delivery capabilities. The N-terminal addition of an octanoyl group reduced the particle size and polydispersity. The C-terminal polyarginine extension allowed the formation of nanoparticles with greater stability and smaller sizes with siRNA loading compared to those for the original and other variant peptides. The resulting peptide amphiphile PA8 effectively delivered siRNA into AsPC-1 pancreatic cancer cells. We developed a peptide amphiphile (PA) consisting of a hydrophobic alkyl chain, a hydrophobic GAVIL peptide, and a hydrophilic polyarginine. The existence of an alkyl chain promoted the self-assembly of PA to form nanoparticles. To the surface of nanoparticles, siRNA could be attached, producing positively charged nanocomplexes that effectively internalize into cancer cells.