Co-delivery of doxorubicin and quercetin with Angiopep-2 modified graphene oxide for targeted chemo-photothermal therapy of glioblastoma

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options due to poor drug penetration across the blood-brain barrier (BBB). As combined treatment with doxorubicin and quercetin exhibited synergistic cytotoxic effects against U87 glioblastoma cells, graphene oxide (GO) can be employed to deliver these drugs, thereby enhancing their bioavailability during chemotherapy. GO can also serve as an efficient photothermal agent under near-infrared (NIR) irradiation. In this study, we functionalize GO with the Angiopep-2 peptide ligand to prepare a GOA nanocarrier. After co-loading quercetin and doxorubicin, the GOA/Q/D nanoplatform can enable BBB crossing/tumor targeting, pH-responsive drug delivery, and efficient NIR-mediated photothermal conversion for targeted chemo-photothermal therapy of GBM. Physicochemical characterization confirmed successful nanoparticle fabrication, favorable stability, and efficient drug loading and controlled drug release. Confocal microscopy and flow cytometry analyses indicate enhanced cellular uptake of GOA by U87 cells and intracellular doxorubicin accumulation. The integration of synergistic chemotherapy and NIR-induced photothermal therapy with GOA/Q/D resulted in significantly increased apoptosis and tumor cell death. In vivo studies confirmed Angiopep-2-mediated brain accumulation in healthy and tumor-bearing nude mice after intravenous administration. Therapeutic evaluation further demonstrated significantly inhibited tumor growth and prolonged survival in glioma-bearing mice treated with GOA/Q/D through intravenous injection plus NIR laser irradiation at the tumor site. Collectively, the integration of targeted delivery, synergistic dual-drug chemotherapy, and photothermal activation resulted in markedly improved therapeutic efficacy, underscoring the potential of chemo-photothermal therapy for the targeted treatment of glioblastoma.