Co-delivery of dasatinib and miR-30a by liposomes targeting neuropilin-1 receptors for triple-negative breast cancer therapy

Abstract

Combinational therapy to treat triple-negative breast cancer (TNBC) by concomitantly influencing different cellular pathways has attracted attention recently. In the present study, co-delivery of dasatinib and miR30a by means of CRGDK-targeted lipopolyplexes was conducted to enhance the inhibition of cell proliferation and migration. For this purpose, we condensed the cationic copolymer poly(1-vinylimidazole-co-2-aminoethyl methacrylate) with miR-30a to form polyplexes. Next, the polyplexes and dasatinib were loaded in targeted liposomes via a thin-film hydration method to form final lipopolyplexes. Physicochemical properties of the nano-carriers were evaluated, and their influence on cellular uptake, cytotoxicity, cell migration, apoptosis induction, and Notch-1 mRNA levels as well as their transfection efficiency were assessed in the MDA-MB-231 cell line. Targeted dasatinib-loaded lipopolyplexes exhibited superior cell proliferation and migration inhibition and cellular uptake than dasatinib, polyplexes and non-targeted lipopolyplexes. Moreover, in comparison with non-targeted lipopolyplexes and polyplexes, targeted lipopolyplexes significantly transfected MDA-MB-231 cells and downregulated Notch-1 mRNA.