Ultrathin Metal-Organic-Layer Mediated Radiotherapy-Radiodynamic Therapy

• DOI: 10.1016/j.matt.2019.06.007
• Publication Date: 2019-08-28T15:00:21Z
• Authors: Kaiyuan Ni; Guangxu Lan; Christina Chan; Xiaopin Duan; Nining Guo; Samuel S. Veroneau; Ralph R. Weichsel...; Wenbin Lin
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Summary 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 reactivating antitumor 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 CBI led to robust abscopal effects on a series of bilateral models of colon, head and neck, and breast cancers, as well as significant antimetastatic effects on an orthotopic model of breast cancer.