International Journal of Nanomedicine (Dec 2023)
Synergistically Enhancing Immunotherapy Efficacy in Glioblastoma with Gold-Core Silica-Shell Nanoparticles and Radiation
Abstract
Shuo-Fu Chen,1,* Min Kau,2,* Yu-Chi Wang,2 Ming-Hong Chen,3 Fu-I Tung,4,5 Mei-Hsiu Chen,6 Tse-Ying Liu2 1Department of Heavy Particles & Radiation Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Division of Neurosurgery, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 4Department of Orthopedics, Yang-Ming Branch, Taipei City Hospital, Taipei, Taiwan; 5Department of Health and Welfare, College of City Management, University of Taipei, Taipei, Taiwan; 6Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Tse-Ying Liu, Department of Biomedical Engineering, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei, 112304, Taiwan, Tel +8862 28267923, Email [email protected]: 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@SiO2 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@SiO2 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.Keywords: brain cancer, silica, gold, atezolizumab, radiation therapy
