Combined delivery of BCNU and VEGF siRNA using amphiphilic peptides for glioblastoma

Combined delivery of chemical drug and therapeutic gene has been introduced as an efficient method for the treatment of cancers such as glioblastoma. In this study, bis-chloroethylnitrosourea (BCNU) and vascular endothelial growth factor (VEGF) small interfering RNA (VEGFsiRNA) were co-delivered into C6 glioblastoma cells using a non-toxic peptide-based carrier. The R3V6 peptides, which are composed of 3-arginine and 6-valine, formed self-assembled micelles in aqueous solution. BCNU, a hydrophobic anti-cancer drug, was loaded into the hydrophobic core of the micelles, forming BCNU-loaded R3V6 micelles (R3V6-BCNU). In gel retardation assay, R3V6-BCNU formed a stable complex with siRNA. In vitro transfection assay showed that the VEGF-siRNA/R3V6-BCNU complex had the highest transfection efficiency into C6 cells at a 1: 20 weight ratio (VEGF-siRNA: R3V6-BCNU). In addition, the VEGF-siRNA/R3V6BCNU complexes had higher delivery efficiency than lipofectamine or naked siRNA. VEGF expressions were remarkably decreased by transfection of the VEGF-siRNA/R3V6 or VEGFsiRNA/ R3V6-BCNU complexes. Furthermore, R3V6-BCNU delivered BCNU more efficiently into the cells than BCNU only. Therefore, R3V6 delivered both VEGF-siRNA and BCNU efficiently into the glioblastoma cells. The results suggest that R3V6-BCNU may be useful for combined delivery of siRNA and chemical drug into cancer cells.