Cerenkov Luminescence-Induced NO Release from 32P-Labeled ZnFe(CN)5NO Nanosheets to Enhance Radioisotope-Immunotherapy
Longlong Tian,1 Yaxing Wang,2 Lele Sun,1 Jun Xu,1 Yu Chao,1 Kai Yang,2 Shuao Wang,2 and Zhuang Liu,1*
1Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China
2State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu 215123, China
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.