Abstract A038: Modified RVG Functionalized Liposome Gold Nanoparticles for specific microRNA delivery Against Glioblastoma

Abstract Introduction: Glioblastoma (GBM) is the most aggressive and lethal type of primary brain tumors, with a median survival time of only 12 to 15 months after diagnosis. Despite numerous research efforts, treatment options have remained largely unchanged for decades, with the Stupp Protocol combining surgery, radiotherapy, and chemotherapy remaining as the gold standard. This persistent poor prognosis underscores the need for novel therapy approaches. MicroRNAs (miRNAs), small non-coding RNA molecules that regulate gene expression post-transcriptionally, have gained attention as potential therapeutic targets for GBM. Specifically, miR-92b is notably overexpressed in GBM tissue samples and GBM cell lines, contributing to tumor growth, resistance to treatment, and increased malignancy. Targeting miR-92b with Oligonucleotide MicroRNA Inhibitors (OMIs) has demonstrated promising tumor-suppressing effects in preclinical models. However, delivering these inhibitors efficiently across the blood-brain barrier (BBB) remains a significant challenge. To overcome this, we developed five modified Rabies Virus Glycoprotein (RVG) peptides that bind to α7 nicotinic acetylcholine receptors expressed on both BBB and GBM cells to facilitate targeted delivery. Methods: The wild-type and modified RVG peptide sequences were bound to liposomal nanoparticles to achieve targeted delivery. OMIs against miR-92b were then encapsulated inside RVG-functionalized liposomes, creating the lipid-based nanocarrier system. Results: GBM cells treated with modified RVG functionalized liposomes showed significantly enhanced uptake of the nanoparticle formulation compared to those treated with plain (non-functionalized) or RVG wild-type functionalized liposomes. This indicates that modifications of the RVG peptide enhance both cellular internalization efficiency and the downregulation of miR-92b. These results, along with high stability, are vital factors for successful therapeutic delivery. Conclusion: This study introduces a novel, targeted delivery platform capable of transporting stable miR-92b inhibitors directly to GBM cells. The modified RVG-functionalized gold liposomes offer a promising RNA-based therapeutic strategy for GBM, potentially paving the way for more effective treatments against this aggressive cancer. Citation Format: Diego E. Garcia Ortiz, Angel G. Rodriguez Monroig, Annelis O. Sanchez Alvarez, Fatma A. Valiyeva, Pablo E. Vivas Mejia. Modified RVG Functionalized Liposome Gold Nanoparticles for specific microRNA delivery Against Glioblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A038.