Design and Application of Targeted Exosomes for Glioblastoma Therapy Delivery

Abstract

Background: Glioblastoma multiforme (GBM) is the most aggressive type of primary brain cancer. The major challenge with glioblastoma treatment is its highly invasive nature, which renders complete surgical eradication impossible. Hence, adjuvant chemoradiotherapy is inevitable. Since the blood-brain barrier (BBB) provides a critical impediment to effective therapeutic delivery to the tumor due to its restrictive endothelial seal, here we aimed at utilizing exosomes, naturally secreted vesicles with an innate ability to traverse the BBB, as a strategy to overcome this limitation and as a promising vehicle for the delivery of microRNA-based therapeutics. Methods: Human HEK293T cells were genetically modified to express the exosomal membrane protein CD63 as a chimera containing different, GBM-targeting peptides. The proper production of exosomes was validated in vitro. Subsequently, a mouse model of intracranial GBM was used to confirm selective exosome delivery. Conclusion: EVs provide a potential vehicle for the targeted delivery of miRNAs through the BBB, which could offer an opportunity for GBM gene therapy delivery. Future Directions: the next steps will involve fitting tumor-targeting exosomes with an appropriate miRNA cargo, delivering them in the same approach to the glioma-bearing mouse model, and monitoring their tumor-suppressive potential.