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

Radiotherapy (RT) is a widely used way for cancer treatment. However, the efficiency of RT may come with various challenges such as low specificity, limitation by resistance, high dose and so on. Nitric oxide (NO) is known a very effective 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 efficient NO source, is coupled to Ag(2)S quantum dots (QDs). NO could be generated and released from the Ag(2)S QDs effectively under the NIR irradiation due to the thermal effect. In addition, Ag is also a type of heavy metal that can benefit the RT therapy. We demonstrate that Ag(2)S NO delivery platforms remarkably maximize radiotherapy effects 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 Ag(2)S NO delivery platforms. Our results suggest the promise of Ag(2)S NO delivery platforms for multifunctional cancer radioimmunotherapy. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40820-020-00431-3) contains supplementary material, which is available to authorized users.