Abstract
PURPOSE: Glioblastoma is a highly aggressive brain tumor with universally poor outcomes. Recent progress in immune checkpoint inhibitors has led to increased interest in their application in glioblastoma. Nonetheless, the unique immune milieu in the brain has posed remarkable challenges to the efficacy of immunotherapy. We aimed to leverage the radiation-induced immunogenic cell death to overcome the immunosuppressive network in glioblastoma. METHODS: We developed a novel approach using the gold-core silica-shell nanoparticles (Au@SiO(2) NPs) in combination with low-dose radiation to enhance the therapeutic efficacy of the immune checkpoint inhibitor (atezolizumab) in brain tumors. The biocompatibility, immune cell recruitment, and antitumor ability of the combinatorial strategy were determined using in vitro assays and in vivo models. RESULTS: Our approach successfully induced the migration of macrophages towards brain tumors and promoted cancer cell apoptosis. Subcutaneous tumor models demonstrated favorable safety profiles and significantly enhanced anticancer effects. In orthotopic brain tumor models, the multimodal therapy yielded substantial prognostic benefits over any individual modalities, achieving an impressive 40% survival rate. CONCLUSION: In summary, the combination of Au@SiO(2) NPs and low-dose radiation holds the potential to improve the clinical efficacy of immune checkpoint inhibitors. The synergetic strategy modulates tumor microenvironments and enhances systemic antitumor immunity, paving a novel way for glioblastoma treatment.