Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma

<jats:title>Abstract</jats:title><jats:p>Treatments of glioblastoma (GBM) have not been very effective, largely due to the inefficiency of drugs in penetrating the blood brain barrier (BBB). In this study, we investigated the potential of exosome‐coated doxorubicin (DOX)‐loaded nanoparticles (ENP<jats:sub>DOX</jats:sub>) in BBB penetration, inducing immunogenic cell death (ICD) and promoting survival of GBM‐bearing mice. DOX‐loaded nanoparticles (NP<jats:sub>DOX</jats:sub>) were coated with exosomes prepared from mouse brain endothelial bEnd.3 cells. ENP<jats:sub>DOX</jats:sub> cellular uptake was examined. Penetration of ENP<jats:sub>DOX</jats:sub> through the BBB was tested in an in vitro transwell system and a GBM mouse model. The effects of ENP<jats:sub>DOX</jats:sub> in inducing apoptosis and ICD were assessed. Finally, the efficacy of ENP<jats:sub>DOX</jats:sub> in the treatment of GBM‐bearing mice was assessed. ENP<jats:sub>DOX</jats:sub> was taken up by bEnd.3 cells and could penetrate the BBB both in vitro and in vivo. In vitro, END<jats:sub>DOX</jats:sub> induced apoptosis and ICD of glioma GL261 cells. Systemic administration of ENP<jats:sub>DOX</jats:sub> resulted in maturation of dendritic cells, activation of cytotoxic cells, altered production of cytokines, suppressed proliferation and increased apoptosis of GBM cells in vivo and prolonged survival of GBM‐bearing mice. Our findings indicate that ENP<jats:sub>DOX</jats:sub> may be a potent therapeutic strategy for GBM which warrants further investigation in clinical application.</jats:p>