Targeted Delivery of siRNA through Nanocomplex using Specific Fusion
Peptides for Breast Cancer Treatment
Abstract
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 exhibits difficulties in specific
cellular uptake and instability. Therefore, we designed novel fusion
peptides (RS and RT) for an efficient, stable, and specific delivery of
small RNAs. Both RS and RT peptides could form self-assembled
nanocomplexes via electrostatic attraction. 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 nanocomplexes could be
expected to become a promising siRNA delivery platform for the treatment
of breast cancer or other cancers.