microRNA-Based Polymer Therapeutics for Combating Glioblastoma

Glioblastoma Multiforme (GBM) is one of the most aggressive cancers. The median survival with current standard-of-care radiation and chemotherapy is about 14 months. GBM can be difficult to treat due to heterogeneity in cancer cell population. MicroRNA-based drugs have rapidly become a vast and burgeoning field. Besides being potent, microRNA (miR) can be used to target many genes involved in cellular signaling pathways. In this work, we focused on miR-34a, which is known for its key role in important oncogenic pathways and its tumor suppression capability. In vivo delivery of miR remains a crucial challenge for its therapeutic success. To bypass these shortcomings, we developed polymeric nanogels which are based on a polyglycerol-scaffold.

We evaluated the capability of several nanogel derivatives (NGs) to encapsulate miR-34a and neutralize its negative charge in a dose-dependent manner. A substantial silencing and anticancer effect was accomplished in vitro with our miR-nanogel polyplexes, as measured by luciferase reporter assay and proliferation assays.

Administration of miR-34a/NG nanoplexes to human U-87 MG GBM tumors inoculated in SCID mice, significantly inhibited tumor growth at day 20 (379±175 mm³), as opposed to treatment with the non-targeting miR/NG nanoplex (883±‎580 mm³‎) and the control group who received the vehicle saline (1197‎±359 mm³‎). We expect that this therapeutic approach will be the basis for a new promising drug to treat GBM.

Key words: microRNA, Glioblastoma, nanogels, polymer therapeutics.