Curcumin loaded DA3 as a carrier of the antagomir for the inhibition of microRNA-21 in glioblastoma

Abstract

Glioblastoma multiform (GBM) is one of the most common malignant primary brain tumors. It was previously reported that microRNA21 (miR-21), one of the glioma-specific microRNA, was an anti-apoptosis factor. miR-21 reduced the expression of tumor suppressor genes such as PDCD-4 and PTEN. Antagomir against miR-21 (AMO-21) may inhibit the action of miR-21 and reduce the growth of glioblastoma. In this study, deoxycholic acid conjugated polyethylenimine (DA3) was used as a carrier of miR-21. DA3 is an amphiphilic molecule with hydrophilic polyethylenimine and hydrophobic deoxycholic acid. Therefore, DA3 forms micelle in aqueous solution. Curcumin, which has anti-tumor effect, was loaded into the hydrophobic core of DA3 micelle, producing curcumin loaded DA3 (Curcumin-DA3). DA3-Curcumin formed stable complex with antagomir-21. In vitro transfection studies showed that DA3-Curcumin increased the delivery efficiency of antagomir-21 into the C6 rat glioblastoma cells, compared with polyethylenimine and Lipofectamine. Curcumin-DA3 increased the intracellular delivery of curcumin, compared with curcumin only or a simple mixture of DA3 and curcumin complex. As a result, Curcumin-DA3 showed higher anti-tumor effect than the controls. Furthermore, the delivery of antagomir-21(AMOs) with Curcumin-DA3 reduced viability of the C6 glioblastoma cells. Therefore, the complex of Curcumin-DA3 and antagomir-21 may be useful for the treatment of glioblastoma as a combination therapy of curcumin and antagomir-21.