Extracellular vesicles: Navigating new frontiers in glioblastoma therapy

The profound challenge in treating glioblastoma (GBM) stems from a confluence of obstacles. The formidable blood-brain barrier (BBB) limits drug access, while the tumor's inherent inter- and intra-tumoral heterogeneity, profound immunosuppression, invasive growth, and frequent recurrence all contribute to dismal prognoses and severely hamper therapeutic efficacy. Extracellular vesicles (EVs), naturally occurring nano-sized messengers between cells, offer a novel therapeutic avenue by addressing these key obstacles. Their inherent ability to cross the BBB, deliver diverse cargo, and modulate the immune system positions them as promising vehicles for targeted drug delivery, immunotherapy, and even cancer vaccination. This review explores the therapeutic potential of various EV subtypes, including those derived from dendritic cells, T cells, brain endothelial cells, and mesenchymal stem cells, emphasizing their unique properties and preclinical successes in GBM models. We discuss current engineering strategies to enhance EV targeting, delivery, and therapeutic efficacy, alongside the emerging potential of EV-based cancer vaccines for GBM. Finally, we address the challenges and future directions of EV-based therapies for GBM, including standardized isolation and characterization protocols, scalable production, and rigorous safety assessments. Despite these challenges, the burgeoning field of EV research holds immense promise for transforming GBM treatment paradigms and improving patient outcomes.