Two-dimensional multifunctional nanosheets as radiosensitizers for chemodynamic/radio-therapy

The hypoxia tumor microenvironment and low radiation attenuation coefficient of tumor tissue usually limit the efficiency of radiotherapy. In this study, a two-dimensional multifunctional nano-sensitizer, CuNS@Pt, was prepared to function as a radiosensitizer, enhancing radiotherapy through multiple mechanisms. Numerous active sites were provided for the deposition of X-ray radiation energy by the in-situ chemical reduction of Pt to create functional hybrids on Cu-based nanosheets. CuNS@Pt catalyzed high concentration of endogenous hydrogen peroxide to generate oxygen in tumor microenvironment, alleviating the physiological environment of hypoxic tumors. Additionally, CuNS could reduce the content of intrinsic glutathione (GSH) and catalyze hydrogen peroxide to form hydroxyl radicals (·OH). The generated ·OH could damage mitochondria and destroy redox homeostasis due to the functional inclusion of Cu species, thereby achieving chemodynamic therapy and further improving the radiation effect. Both in vivo and in vitro experiments showed that the nano sensitizer effectively improved the therapeutic efficiency of radiotherapy and had good biological safety. All in all, this study provides a pragmatic and doable platform for maximizing the efficacy of RT in cancer. This study also highlights the future research value of two-dimensional nanomaterials.