Cerenkov Luminescence-Induced NO Release from 32P-Labeled ZnFe(CN)5NO Nanosheets to Enhance Radioisotope-Immunotherapy

Summary The combination of radiotherapy with immunotherapy has emerged as a promising combinational therapeutic methodology. The efficacies of both types of therapies, however, are hampered by the abnormal tumor microenvironment (TME) with hypoxic and immunosuppressive features. Herein, we discover that by mixing zinc ions with sodium nitroprusside, a clinical anti-hypertensive drug, ZnFe(CN)5NO single-layer nanosheets can be obtained. Interestingly, after being labeled with 32P by simple mixing, the 32P-induced Cerenkov luminescence stimulated persistent release of NO from nanosheets. Owing to the modulation of hypoxic immunosuppressive TME by NO, such 32P-labeled nanosheets are able to completely eliminate local tumors after local administration, and proffer a strong abscopal effect after being combined with immune-checkpoint blockade therapy. Our work presents a unique 2D nanoplatform comprising Zn2+ and a clinical drug to enable chelator-free radiolabeling, Cerenkov luminescence-triggered NO release, effective TME modulation, and enhanced combination radioisotope-immunotherapy are promising for tumor metastasis treatment.