Magnetic Nanoparticles as a Carrier of dsRNA for Gene Therapy

Abstract

Glioma belongs to the most aggressive and lethal types of cancer. Glioblastoma multiforme (GBM), the most common type of malignant gliomas, is characterized by a poor prognosis and remains practically incurable despite aggressive treatment such as surgery, radiotherapy, and chemotherapy. Brain tumor cells overexpress a number of proteins that play a crucial role in tumorigenesis and may be exploited as therapeutic targets. One such target can be an extracellular matrix glycoprotein—tenascin-C (TN-C). Downregulation of TN-C by RNA interference (RNAi) is a very promising strategy in cancer therapy. However, the successful delivery of naked double-stranded RNA (dsRNA) complementary to TN-C sequence (ATN-RNA) requires application of delivery vehicles that can efficiently overcome rapid degradation by nucleases and poor intracellular uptake. Here, we present a protocol for application of MNP@PEI as a carrier for ATN-RNA to GBM cells. The obtained complexes consisted of polyethyleneimine (PEI)-coated magnetic nanoparticles combined with the dsRNA show high efficiency in ATN-RNA delivery, resulting not only in significant TN-C expression level downregulation, but also impairing the tumor cells migration.