Engineered exosomes with enhanced stability and delivery efficiency for glioblastoma therapy

Due to the blood-brain barrier (BBB), the application of chemical drugs for glioblastoma treatment is severely limited. Recently, exosomes have been widely applied for drug delivery to the brain. However, the differences in brain targeting efficiency among exosomes derived from different cell sources, as well as the premature drug leakage during circulation, still limit the therapeutic efficacy. Here, we designed a functional oligopeptide-modified exosome loaded with doxorubicin (Pep2-Exos-DOX) for glioblastoma treatment. BV2 mouse microglial cell line was selected as the exosome source due to the favorable BBB penetration. To avoid drug release in the circulation, a redox-response oligopeptide was designed for incorporation into the membranes of exosomes to lock the drug during circulation. The enrichment of the drug in glioblastoma was confirmed. Pharmacodynamic evaluation showed Pep2-Exos-DOX possessed significant anti-cancer activity against glioblastoma as well as relative biosafety. This exosome-based drug delivery system modified with redox-response oligopeptides provides us a novel strategy for brain diseases treatment. A functional oligopeptide-modified exosome derived from microglia cells is synthesized to deliver doxorubicin into the brain for the treatment of glioblastoma. The nature of exosomes improves the BBB penetration ability of the system, and the oligopeptide contributes to avoiding the early release of drug in the circulation. This study provides a novel drug delivery strategy for brain diseases. [Display omitted] •BV2-derived exosomes possess favorable BBB penetration and glioma targeting effects.•The novel peptides crosslinking avoids premature drug release in circulation.•Elevated GSH in glioma microenvironment leads to responsive drug release.•The engineered exosomes exbibit excellent therapeutic efficacy against glioma.