Fig. 4

Nanoscale metal–organic framework (nMOFs) enable synergistic radiotherapy–radiodynamic therapy (RT–RDT) and immunotherapy using extremely low doses of X-rays. Indoleamine 2,3-dioxygenase inhibitor nMOF (IDOi@nMOF) was intratumorally injected into the right-side tumors of mice bearing bilateral subcutaneous tumors. Upon low-dose X-ray irradiation, IDOi@nMOF eradicated the right (irradiated) tumors in two ways: via synergistic RT–RDT, which caused both apoptosis and necrosis of cancer cells, and via immunotherapy by IDOi released from the nMOF, which overcame the suppressive tumor microenvironment by preventing catabolism of tryptophan (Trp) to kynurenine (Kyn) and subsequent T-cell anergy. Importantly, systemic IDOi activity combined with local RT–RDT induced immunogenic cell death, and antigen release led to the effective expansion and tumor infiltration of functional CD8⁺ T cells, which effectively suppressed or eradicated the left-side (untreated) tumors (reprinted with permission from Ref [58]; © 2018 Nature Publishing Group)