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

Abstract

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 (VEGF-siRNA) 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/R3V6-BCNU complexes had higher delivery efficiency than lipofectamine or naked siRNA. VEGF expressions were remarkably decreased by transfection of the VEGF-siRNA/R3V6 or VEGF-siRNA/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.

Peptide Micelle-Mediated Delivery of Tissue-Specific Suicide Gene and Combined Therapy with Avastin in a Glioblastoma Model

“…Although these vectors can deliver DNA into the cells in vitro , they have high toxicity, limiting their in vivo application . To avoid high toxicity of the carriers, short amphiphilic peptide micelles were developed for gene delivery . The R7L10 amphiphilic peptide forms micelles in aqueous solution.…”

“…10,11 To avoid high toxicity of the carriers, short amphiphilic peptide micelles were developed for gene delivery. [12][13][14][15] The R7L10 amphiphilic peptide forms micelles in aqueous solution. R7L10 is composed of a 7-arginine stretch and a 10-leucine stretch.…”

Miktoarm Star Micelles Containing Curcumin Reduce Cell Viability of Sensitized Glioblastoma

“…Micellar nanodelivery systems for several drugs for the treatment of GBM have been developed and reviewed [5]. For instance, a micellar system based on amphiphilic peptides and incorporating bis-chloroethylnitrosourea (BCNU) and vascular endothelial growth factor (VEGF) small interfering RNA (VEGF-siRNA), was prepared and tested in C6 glioblastoma cells [6]. The micelles showed better delivery of BCNU into the cells and remarkably reduced expression of VEGF.…”

Peptide Micelles for Anti-cancer Drug Delivery in an Intracranial Glioblastoma Animal Model

“…8,9 In vitro studies showed that BCNU-loaded R3V6 (R3V6-BCNU) more efficiently delivered siRNA or plasmid DNA (pDNA) than did empty R3V6 micelles. 10 Furthermore, the R3V6-BCNU/pDNA complex were more toxic to the cancer cells than was the mixture of BCNU and pDNA.…”

“…10,11 The improved delivery efficiency of plasmid DNA and siRNA may be due to the stabilization of the micelle structure by provision of stronger hydrophobic cores such as that in BCNU.…”