Additive Polyplexes to Undertake siRNA Therapy against CDC20 and Survivin in Breast Cancer Cells.

Abstract

Small interfering RNA (siRNA) delivered to silence overexpressed genes associated with malignancies is a promising targeted therapy to decrease the uncontrolled growth of malignant cells. To create potent delivery agents for siRNA, here we formulated additive polyplexes of siRNA using linoleic acid-substituted polyethylenimine and additive polymers (hyaluronic acid, poly(acrylic acid), dextran sulfate, and methyl cellulose) and characterized their physicochemical properties and effectiveness. Incorporating polyanionic polymer along with anionic siRNA in polyplexes was found to decrease the ζ-potential of polyplexes but enhance the cellular delivery of siRNA. The CDC20 and survivin siRNAs delivered by additive polyplexes showed promising efficacy in breast cancer MDA-MB-231, SUM149PT, MDA-MB-436, and MCF7 cells. However, the side effects of the siRNA delivery were observed in nonmalignant cells, and a careful formulation of siRNA/polymer polyplexes was needed to minimize side effects on normal cells. Because the efficacy of siRNA delivery by additive polyplexes was independent of breast cancer phenotypes used in this study, these polyplexes could be further developed to treat a wide range of breast cancers.