초록 |
Gene silencing using siRNAs can be a new potent strategy to treat many incurable diseases at the genetic levels. However, treatments using siRNAs essentially require an efficient and safe method of delivering siRNAs into cells while maintaining stability. Therefore, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Fusion peptides could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes. According to the results, the nanocomplexes showed evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, even to the HDFn cells of the skin. Moreover, all the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased the retention time of siRNAs at the tumor site. Finally, nanocomplexes demonstrated a significant in vivo gene silencing effect without overt tissue damage, inflammation, and immune cell infiltration. Thus, the new nanocomplex strategy could become a safe and efficient platform for delivering siRNAs into cells and tissues to treat various target diseases through gene silencing. |