The challenge in HER2-overexpressing
breast cancer therapy lies in creating an effective target
therapy to overcome treatment resistance.
Monoclonal antibodies and target gene silencing by
siRNA are two potential strategies that have been widely developed for treating HER2-positive
breast cancer. The
siRNA delivery system is a crucial factor that influences
siRNA therapy's success. In this study,
lipid-based nanoparticles (cationic
niosomes) composed of different
cholesterol-based cationic
lipids were formulated and characterized for delivering
siRNA into HER2-overexpressing
breast cancer cells.
Niosomes containing a trimethylammonium headgroup showed the highest
siRNA delivery efficiency with low toxicity. The myeloid cell leukemia-1 (Mcl-1)
siRNA nioplex treatment significantly decreased
mRNA expression and
breast cancer cell growth. Dual-targeted
therapy, consisting of treatment with an Mcl-1
siRNA nioplex and
trastuzumab (TZ)
solution, noticeably promoted cell-growth inhibition and apoptosis. The synergistic effect of dual
therapy was also demonstrated by computer modeling software (CompuSyn version 1.0). These findings suggest that the developed cationic
niosomes were effective nanocarriers for
siRNA delivery in
breast cancer cells. Furthermore, the Mcl-1 nioplex/TZ dual treatment establishes a synergistic outcome that may have the potential to treat HER2-overexpressing
breast cancer.