Cholesterol modified defense peptide as an EMP2-siRNA delivery system for synergistic immunogene therapy against breast cancer

Abstract Epithelial membrane protein 2 (EMP2) plays crucial roles in cell proliferation, migration, and adhesion. Despite its importance, conventional EMP2 RNAi therapy shows limited efficacy in vivo. We therefore developed a novel RNA-delivery system utilizing self-assembling defense peptide-cholesterol conjugates for efficient EMP2-siRNA transfection. The engineered HH2-siEMP2 nanoparticles exhibited optimal size and positive surface charge, conferring excellent serum stability and enhanced cellular uptake in breast cancer cell lines. These nanoparticles effectively silenced EMP2 expression, leading to significant suppression of tumor migration