Abstract
Checkpoint blockade immunotherapy (CBI) is effective in promoting a systemic immune response against some metastatic tumors. The reliance on the pre-existing immune environment of the tumor, however, limits the efficacy of CBI on a broad spectrum of cancers. Herein, we report the design of a novel nanoscale metal-organic layer (nMOL), Hf-MOL, for effective treatment of local tumors by enabling radiotherapy-radiodynamic therapy (RT-RDT) with low-dose X-rays and, when in combination with an immune checkpoint inhibitor, regression of metastatic tumors by re-activating anti-tumor immunity and inhibiting myeloid-derived suppressor cells. Owing to the reduced dimensionality, nMOLs allow facile diffusion of reactive oxygen species and exhibit superior RT-RDT effects. The synergy of Hf-MOL-enabled RT-RDT immune activation and anti-programmed death ligand 1 (anti-PD-L1) CBI led to robust abscopal effects on a series of bilateral models of colon, head and neck, and breast cancers and significant anti-metastatic effects on an orthotopic model of breast cancer.