Delivery of microRNA-21 antagomir using RAGE-binding peptides as a carrier for glioblastoma gene therapy

Abstract

Glioblastoma is the most common and malignant primary tumor of the brain that has seriously high mortality rate. There were many attempts to develop more progressive and applicable treatments for use in clinical trials in glioblastoma. To target independent pathways for better treatments, focusing on the molecular and genomic mechanism of glioblastoma at the cell levels is needed. Receptor for advanced glycation end products (RAGE) is widely overexpressed in glioblastoma. RAGE/ligand interactions stimulate tumor proliferation, invasion and metastasis and influence to form tumor micro-environments by inducing the vascular endothelial growth factor (VEGF) expression. To reduce the VEGF levels, we used RAGE-binding peptide (RBP) as a tumor suppression material. In addition, RBP was used as a carrier of anti-miRNA-21 oligonucleotides (AMO21) which inhibits miRNA-21, one of the key target molecules for the treatments of glioblastoma. To identify the effectiveness of RBP as a nucleic acid carrier, we performed experiments that revealed complex characteristics and uptake efficiency. Then, we performed in-vivo experiments to evaluate anti-tumor effects of both RBP and AMO21 in glioblastoma rat model. As a result, the RBP showed the possibility that can be useful not only for delivery of AMO21 as a non-toxic carrier also for the therapeutic material of glioblastoma itself.