Synergistically Enhancing Immunotherapy Efficacy in Glioblastoma with Gold-Core Silica-Shell Nanoparticles and Radiation

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@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

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

We are grateful to the Ministry of Science and Technology (MOST 111-2221-E-A49-051-MY2, MOST 111-2811-E-A49A-007-MY2, MOST 111-2314-B-038-094, MOST 110-2622-E-A49A-504, MOST 109-2221-E-010-020-MY2, and MOST 108-2314-B-010-035-MY3) and the Department of Health, Taipei City Government (11201-62-004, and 11101-62-009) for financial support.