Engineered exosomes for targeted glioma therapy: overcoming the blood-brain barrier with nature-inspired nanocarriers

Gliomas mainly glioblastoma multiforme (GBM) are the greatest lethal primary brain tumors, marked by rapid progression, high heterogeneity, and poor therapeutic outcomes. A main challenge in treating gliomas lies in the limited permeability of the blood-brain barrier (BBB), which restricts drug access to the tumor site. Conventional treatment protocols, including surgery, radiotherapy, and the Stupp regimen, offer only modest survival aids due to drug resistance and inefficient delivery. Recently, nanotechnology-based approaches have gained attention for enhancing drug transport across the BBB. Among them, exosomes endogenous extracellular vesicles have emerged as promising nanocarriers due to their innate biocompatibility, low immunogenicity, and natural ability to cross the BBB. These vesicles can be planned to deliver therapeutic agents selectively to tumor cells and modulate the tumor microenvironment (TME), influencing processes as well as angiogenesis, immune evasion, and intercellular signaling. This review articulates the innovative contributions of exosome-based drug delivery systems in glioma management, highlighting recent advancements in bioengineering approaches and their dual role in treatment and diagnostics (theranostics). By speaking the biological barriers to drug delivery and enhancing targeted therapeutic effects, exosomes represent a significant leap forward in precision medicine for glioma therapy. Additional clinical and translational research is crucial to fully realize the potential of exosomes as effective delivery systems in glioma treatment.