Targeted delivery of self-assembled nanocomplex between fusion peptides and siRNAs for breast cancer treatment

Breast cancer is one of the serious diseases and has the second-highest mortality in women worldwide. RNA interference has been developed as a promising way of specific cancer treatment by silencing oncogenes efficiently. However, small RNAs exhibit difficulties in specific cellular uptake and instability. Therefore, we developed novel self-assembled nanocomplexes between newly designed fusion peptides and small RNAs for an efficient, stable, targeted delivery to breast cancer cells. Designed R-11-SP82 (RS) and R-11-TT1 (RT) peptides could form self-assembled nanocomplexes via electrostatic attraction. As a result, RS nanocomplexes exhibited prolonged stability, enhanced cellular uptake, and target gene silencing by siRNAs to MDA-MB-231 breast cancer cells. Moreover, RS nanocomplexes successfully inhibited breast cancer cell growth via specific and efficient siRNA delivery. Furthermore, in vitro and in vivo safety tests showed negligible cytotoxicity and neither tissue damage nor significant inflammatory cytokine release. Therefore, the RS nanocomplex strategy could be expected to become a promising siRNA delivery platform for treating breast cancer or other cancers.