Locoregional Delivery of miRNAs for Glioblastoma Treatment: A Systematic Review of Advances in Delivery Systems

Glioblastomas represent the most aggressive and lethal form of primary brain cancer and continue to pose a major challenge to global health. MicroRNAs (miRNAs), as central regulators of gene expression, are intimately involved in the initiation, progression, and therapeutic resistance of numerous malignancies, including glioblastoma. Therefore, this class of non-coding RNAs are considered to be valuable candidates for innovative therapeutic strategies. However, despite many promising preclinical studies, miRNA-based therapies have yet to be translated into routine clinical practice. In the context of glioblastoma, one of the principal obstacles to the effective delivery of synthetic miRNA therapy is their limited ability to cross the blood-brain barrier (BBB). To address this challenge, a variety of locoregional delivery strategies have been developed in recent years. In this review, we provide a detailed discussion and a state-of-the-art overview of these local delivery methods in the context of glioblastoma treatment, with a specific emphasis on their application for delivering miRNA-based therapeutic oligonucleotides, formulated either with or without synthetic nanoparticles.