Delivery of biologically active miR-34a in normal and cancer mammary epithelial cells by synthetic nanoparticles

Abstract

Functional RNAs, such as microRNAs, are emerging as innovative tools in the treatment of aggressive and incurable cancers. In this study, we explore the potential of silica dioxide nanoparticles (SiO₂NPs) in the delivery of biologically active miRNAs. Focusing on the tumor-suppressor miR-34a, we evaluated miRNAs delivery by SiO₂NPs into the mammary gland, using in vitro as well as in vivo model systems. We showed that silica nanoparticles can efficiently deliver miR-34a into normal and cancer epithelial cells grown in culture without major signs of toxicity. Delivered miRNA retained the ability to silence artificial as well endogenous targets and can reduce the growth of mammospheres in 3D culture. Finally, miR-34a delivery through intra-tumor administration of SiO₂NPs leads to a reduced mammary tumor growth. In conclusion, our studies suggest that silica nanoparticles can mediate the delivery of miR-34a directly into mammary tumors while preserving its molecular and biological activity.

Keywords: Breast cancer; Mammary gland; Nanoparticles; RNA delivery; Stem cells; miRNA.