Synergistic Local Combination of Radiation and Anti-Programmed Death Ligand 1 Immunotherapy Using Radiation-Responsive Splintery Metallic Nanocarriers.

Radiation therapy (RT)-mediated tumor immunogenicity offers an opportunity for synergistic combination RT and immunotherapy. One of the challenges in the clinic is to attain the optimum efficacy of combination RT and immunotherapy with minimized overlapping toxicities. Here, to achieve synergistic therapeutic efficacy of combinational RT and anti-programmed death ligand 1 (aPD-L1) immunotherapy, RT-responsive splintery snowflake-like Au nanocarriers (S-AuNC) were synthesized with a method for hierarchical bimetallic supra-nanostructures. Primary Au nanocrystals interconnected with Ag nanocrystals in S-AuNC showed RT-responsive structural deformation resulting in RT-triggered release of cargo aPD-LI in S-AuNC. The local combination of RT and aPD-L1 loaded S-AuNC significantly enhanced the immunogenic cell death for tumor microenvironment conversion. RT-triggered local aPD-L1 release allowed a controlled spatiotemporal combination RT and aPD-L1 immunotherapy resulting in a synergistic anticancer adaptive immune response with minimized systemic immune-related adverse effects.