Near-Infrared Light-Responsive Nitric Oxide Delivery Platform for Enhanced Radioimmunotherapy

Radiotherapy(RT) is a widely used way for cancer treatment. However, the e ciency of RT may come with various challenges such as low specificity, limitation by resist-ance, high dose and so on. Nitric oxide(NO) is known a very e ective radiosensitizer of hypoxic tumor. However, NO cannot circulate in body with high concentration. Herein, an NIR light-responsive NO delivery system is developed for controlled and precisely release of NO to hypoxic tumors during radiotherapy. Tert-Butyl nitrite, which is an e cient NO source, is coupled to Ag2S quantum dots(QDs). NO could be generated and released from the Ag2S QDs e ectively under the NIR irradiation due to the thermal e ect. In addition, Ag is also a type of heavy metal that can benefit the RT therapy. We demonstrate that Ag2S NO delivery platforms remarkably maximize radiotherapy e ects to inhibit tumor growth in CT26 tumor model. Furthermore, immunosuppressive tumor microenvironment is improved by our NO delivery system, significantly enhancing the anti-PD-L1 immune checkpoint blockade therapy. 100% survival rate is achieved by the radio-immune combined therapy strategy based on the Ag2S NO delivery platforms. Our results suggest the promise of Ag2S NO delivery platforms for multifunctional cancer radioimmunotherapy.