Abstract 5754: Targeting miR-92b with peptide-modified liposomes for glioblastoma treatment

Abstract

Abstract Focusing on enhancing drug delivery to the brain, we aim to optimize a nanocarrier system with a specific focus on glioblastoma (GBM). This involves the utilization of spherical nucleic acids (SNAs) enclosed in peptide-modified liposomes, a configuration previously proven to effectively penetrate the blood-brain barrier (BBB) in a GBM mouse model. Our objective is to enhance the nanocarrier's treatment load by optimizing the attachment of oligonucleotide-modified gold nanoparticles (OMI) to the SNAs. MicroRNAs (miRNAs) play crucial roles in GBM pathogenesis, with miR-92b identified as overexpressed in various cancers, including GBM. Previous research from our lab implicated miR-92b in targeting proteins (FBXW7 & SKP2) in the ubiquitination pathway. RNA sequencing confirmed the significance of these pathways. RNA sequencing of miR-92b inhibition in the U87 GBM cell line revealed impacts on cell cycle, apoptosis, DNA repair, and multiple cancer-related pathways. We successfully modified the gold nanoparticle size from 15 nm to 5 nm, increasing the surface area and improving OMI attachment efficiency from less than 5% to 50%. This alteration significantly enhances drug loading in the nanocarrier, providing a promising platform for clinical applications. Characterization of the optimized peptide-modified liposomes reassured the retention and potential improvement of original features related to nanoparticle size and internalization in cell cultures. Future in vivo experiments, utilizing a GBM mouse model, will assess the therapeutic effect of inhibiting miR-92b using peptide-modified liposomes as a drug delivery system. Our multifaceted approach, involving nanocarrier optimization and miR-92b inhibition, holds promise for developing an effective treatment strategy against GBM. The presented results highlight the potential translational impact of our research in addressing the challenges associated with GBM therapy. Citation Format: Annelis Odette Sánchez-Álvarez, Fatima Valiyeva, Pablo E. Vivas-Mejia. Targeting miR-92b with peptide-modified liposomes for glioblastoma treatment [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 5754.