Rational modification of oligoarginine for highly efficient siRNA delivery: structure-activity relationship and mechanism of intracellular trafficking of siRNA

The complexes of siRNA/stearyl-(histidine)n-(arginine)8 (n > 12) induced outstanding knockdown efficiency without any cytotoxicity, where oligoarginine can bind to the cell surface with high affinity; stearyl modification has significantly improved the cellular uptake of siRNA; the endosomal escape of siRNA induced by the peptides was only from “proton-sponge” effect induced by the oligohistidine segments.240