Nano-mediated delivery of double-stranded RNA for gene therapy of glioblastoma multiforme

• DOI: 10.1371/journal.pone.0213852
• Publication Date: 2019-03-19T17:51:20Z
• Authors: Małgorzata Grabowska; Bartosz F. Grześk...; Kosma Szutkowski; Dariusz Wawrzyniak; Paweł Głodowicz; Jan Barciszewski; Stefan Jurga; Katarzyna Rolle; Radosław Mrówczyński
• Keywords: 0303 health sciences; Brain Neoplasms; Science; Q; R; Tenascin; Genetic Therapy; Transfection; Magnetic Resonance Imaging; 3. Good health; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Medicine; Humans; Polyethyleneimine; RNA Interference; RNA, Messenger; RNA, Small Interfering; Glioblastoma; Magnetite Nanoparticles; Research Article; Cell Proliferation; RNA, Double-Stranded

Glioblastoma multiforme (GBM) is the most common type of malignant gliomas, characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fueled a search for new therapeutic targets and treatment modalities. Here we report new approach towards RNA interference therapy of glioblastoma multiforme based on the magnetic nanoparticles delivery of the double-stranded RNA (dsRNA) with homological sequences to mRNA of tenascin-C (TN-C), named ATN-RNA. The obtained nanocomposite consisted of polyethyleneimine (PEI) coated magnetic nanoparticles conjugated to the dsRNA show high efficiency in ATN-RNA delivery, resulting not only in significant TN-C expression level suppressesion, but also impairing the tumor cells migration. Moreover, synthesized nanomaterials show high contrast properties in magnetic resonance imaging (MRI) and low cytotoxicity combining with lack of induction of interferon response. We believe that the present work is a successful combination of effective, functional, non-immunostimulatory dsRNA delivery system based on magnetic nanoparticles with high potential for further application in GBM therapy.