Abstract
Glioblastoma (GBM) is the most aggressive primary cancer with poor survival. In the absence of an effective treatment and a high probability of recurrence, new therapeutic approaches are urgently needed. This study focused on targeting microRNA-10b (miR-10b) highly expressed in GBM cells that has been identified as one of the key drivers of GBM progression. Inhibiting miR-10b using antisense oligonucleotides (ASOs) has shown promise, but its delivery is challenging due to short circulation half-life, degradation by nucleases, and limited blood-brain barrier (BBB) permeability. To overcome these barriers, we employed a magnetic nanoparticle (MN) platform to deliver anti-miR-10b ASOs (MN-anti-miR10b). In addition to serving as a delivery vehicle, these nanoparticles can be used for monitoring delivery using magnetic resonance imaging (MRI). In therapeutic studies in orthotopic models of GBM presented here we used MN-anti-miR10b as well as TTX-MC138, a clinically tested anti-miR10b nanotherapeutic now in Phase I trials in patients with solid (non-GBM) cancers. Both formulations showed efficient delivery, as demonstrated by imaging and improved survival, leading to target inhibition and increased apoptosis. This approach may offer a novel strategy for delivering therapeutics to GBM and improving patient outcomes in one of the most aggressive and treatment-resistant forms of brain cancer.