Abstract 5955: In vivo precision therapy for glioblastoma using a nanodrug targeting microRNA-10b

Abstract Glioblastoma multiforme (GBM) is the most common and aggressive primary brain malignancy, which accounts for about half of all brain tumors. Notably, GBM has been shown to express high levels of microRNA-10b (miR-10b) compared to normal brain tissue, which expresses virtually no miR-10b. Importantly, the mounting body of evidence suggests that suppressing miR-10b in glioblastoma cells disrupts various pathways involved in tumor formation, ultimately leading to the suppression of tumor growth and an increase in apoptosis. We have recently reported that our experimental nanodrug targeting miR-10b (MN-anti-miR10b) effectively suppresses miR-10b expression, inhibits tumor cell migration and invasion, and decreases GBM cell viability in vitro. MN-anti-miR10b consists of an iron oxide core with cross-linked dextran, which acts as the delivery vehicle, and is further conjugated with Cy5.5 fluorophores and therapeutic anti-miR-10b locked-nucleic acid antagomirs. The iron oxide core provides MR imaging contrast while Cy5.5 enables optical imaging modalities in vivo. In this study, U251, human GBM cells, were orthotopically implanted in nude, athymic mice and injected via tail vein with PBS, scrambled antagomir vehicle control (MN-Scr), or MN-anti-miR10b (10 and 20 mg Fe/kg), beginning on day 7 post-implantation. Mice were injected with respective treatments once a week for 6 weeks before assessing changes in survival and expression of miR-10b. In one trial, we assessed the differences in survival between treatment groups after completion of the injection regimen and found that MN-anti-miR10b can increase survival compared to control groups. In another trial, mice were euthanized one week after the last injection and GBM tissues were assessed for miR-10b expression by qRT-PCR. RNA samples extracted from this trial have been submitted for RNA sequencing and differential gene expression analysis will be performed. Here, we demonstrated in vivo that MN-anti-miR10b can efficiently decrease miR-10b expression (57%) and increase median survival (MN-anti-miR10b: 54.5 days vs MN-Scr: 44 days vs PBS: 44 days) compared to PBS and MN-Scr treatment groups. These studies suggest the use of MN-anti-miR10b can be effective in the treatment of GBM in vivo. Citation Format: Bryan Doyun Kim, Elizabeth Kenyon, Ming Chen, Sujan Mondal, Ana de Carvalho, Anna Moore. In vivo precision therapy for glioblastoma using a nanodrug targeting microRNA-10b [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5955.