Extracellular vesicles as delivery vehicles and therapeutic agents for glioblastoma treatment: A systematic review of in vitro and in vivo preclinical studies.

Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy, compounded by the aggressive nature, high invasiveness, and heterogeneity of the disease. Exosomes, a subtype of extracellular vesicles are emerging as promising nanocarrier drug delivery systems to address these limitations. Exosomes released by all cell types can be easily obtained and modified as delivery vehicles or therapeutic agents. A systematic review was conducted to evaluate various methods for exosome isolation, characterization, engineering or modification, drug loading and delivery efficiency, including exosome biodistribution and treatment efficacy. A search of four databases for and studies (2000-,2023) identified 6165 records, of which 23 articles were found eligible and included for analyses. Most studies applied ultracentrifugation (UC) for exosomes isolation. Cancer cell lines being the most frequently used source of exosomes, followed by stem cells. The incubation approach was predominantly utilized to modify exosomes for drug loading. In vivo analysis showed that exosome biodistribution was primarily concentrated in the brain region, peaking in the first 6 h and remained moderately high. Compared to native exosomes and untreated control groups, utilizing modified native exosomes (cargo loaded) for treating glioblastoma disease models led to more pronounced suppression of tumor growth and proliferation, enhanced stimulation of immune response and apoptosis, effective restoration of drug chemosensitivity, increased anti-tumor effect and prolonged survival rates. Modified exosomes whether through incubation, sonication, transfection, freeze-thawing or their combination, improve targeted delivery and therapeutic efficacy against glioblastoma.