Conclusion
Novel fusion peptides could successfully enhance siRNA penetration into cells via a self-assembled complex and resultantly induced mRNA knockdown similar to or better than those of commercialized Lipofectamine™ 2000. The efficiency of mRNA knockdown was synergistically affected by high cellular uptake efficiency, and higher complex stability improved by the increase of arginine length. Co-localization and cellular internalization of siRNA/S-R15 complexes were confirmed peripherally around the nucleus. The primary endocytosis pathway of the siRNA/S-R15 complex was identified as lipid raft-mediated endocytosis. Also, the biosafety of each fusion peptide was confirmed by the cytotoxicity test. Therefore, the safe, stable, and straightforward complex strategy was expected to become a potent and efficient gene delivery platform to treat various target diseases through gene therapy.