The Tumor-Derived Exosomes Enhanced Bevacizumab across the Blood-Brain Barrier for Antiangiogenesis Therapy against Glioblastoma.

Antibody therapy has become a mature cancer treatment strategy, but only one antibody drug, bevacizumab (BEV) has been approved to treat glioblastoma (GBM). The natural blood-brain barrier (BBB) significantly limits the penetration of therapeutic antibodies into the brain. In this study, an antibody delivery platform based on exosomes (EXOs) has been developed, which can cross the BBB and effectively enter the brain tissue to deliver BEV for safe and effective GBM therapy. In vitro experiments have shown that EXO-BEV could efficiently penetrate the BBB and significantly inhibit the migration of endothelial cells. Biodistribution studies in vivo have revealed that EXO serves as an effective carrier for transporting a higher concentration of BEV across the BBB into the brain. Furthermore, in vivo antiglioma experiments have illustrated that the introduction of EXO-BEV into the brain can improve the degeneration of pathological tissues, increase the apoptosis of tumor cells, and significantly extend the survival time of the model animals. All of the results suggested that EXO-BEV could cross the BBB, thereby enhancing the apoptosis of tumor cells and mitigating angiogenesis in GBM. In conclusion, this innovative platform for antibody delivery emerges as a highly promising therapeutic strategy for the clinical treatment of GBM and other neurological disorders.