Fig. 1

Scheme of in vitro and in vivo delivery using siRNA/fusion peptide nanocomplexes. The nanocomplex could be self-assembled via electrostatic attraction between the negatively-charged siRNA and positively-charged arginine-rich region of the fusion peptides, as well as hydrophobic interaction between amphipathic SPACE regions of fusion peptides. The hydrophilic part of the SPACE peptide might have been exposed to the surfaces of the nanocomplexes. The nanocomplex had a diameter of 300 nm and 6-mV zetapotential with a slight positive charge, and it efficiently penetrated the cellular membrane via lipid raft-mediated endocytosis pathway. The siRNAs were released from the nanocomplex in cells, bound to RISC, and mediated effective gene silencing of specific mRNA. The intratumorally administered nanocomplex enhanced retention time of siRNAs at the site of the tumor on the mouse. And, the subcutaneously-injected nanocomplexes with transiently mCherry-expressing cells showed significant in vivo gene silencing effect. The figure was created using BioRender (https://biorender.com)