Exploration of miR-326 delivery via biocompatible polymeric nanoparticles in medulloblastoma: A preliminary study

MicroRNAs play a crucial role in tumorigenesis, functioning as oncogenes or tumor-suppressors while orchestrating the differentiation states of cancer cells. In medulloblastoma, the most common malignant pediatric brain tumor, the downregulation of miR-326 is associated with a loss of tumor suppression that leads to uncontrolled proliferation and survival or de-differentiation. In this study, we explore an innovative approach for microRNA delivery using polycaprolactone/chitosan-based nanoparticles. We evaluate the biocompatibility of the nanocarrier in medulloblastoma cell lines and report results on in vivo nanoparticles administration, demonstrating minimal toxicity in the most exposed organs. In vitro findings reveal that nanoparticles-mediated miR-326 delivery significantly reduces stemness markers (Nanog and Sox2) and promotes neuronal differentiation, as evidenced by increased β3-tubulin expression. These results highlight polycaprolactone-based nanoparticles as a promising platform for miR-326 delivery, establishing a foundation for future investigations on therapeutic strategies in medulloblastoma.