Radionuclide labeled gold nanoclusters boost effective anti-tumor immunity for augmented radio-immunotherapy of cancer

Abstract

Abstract Given the complexity, heterogeneity and metastasis of patient tumors, the combined therapy is usually applied in clinical applications. Internal radioisotope therapy has been an indispensable treatment strategy for primary tumor nowadays. However, the therapeutic effect of internal radioisotope therapy is dissatisfactory for distant tumors or spontaneously metastatic tumors. Herein, we design radionuclide labelled glutathione modified gold nanoclusters (technetium-99m labelled gold nanoclusters (99mTc@Au NCs) and lutecium-177 labelled gold nanoclusters (177Lu@Au NCs)) by simple chelation between glutathione and radionuclide. Such radionuclide labelled gold nanoclusters could not only enhance the therapeutic outcomes of internal radioisotope therapy but also induce anticancer immunity by activation of dendritic cells (DCs). In addition, 177Lu@Au NCs could effectively eliminate primary tumors and suppress the growth of distant tumors when combined with immune checkpoint inhibitors. Furthermore, a long-term immunological memory effect is also observed after internal radioisotope therapy. Importantly, on a clinical-relevant transgenic mice model, we for the first time use such therapeutic strategy to significantly suppress the growth of spontaneously metastatic tumors and lengthen the survival time of the transgenic mice. Our study presents a novel approach for tumor radio-immunotherapy and meanwhile provides a new idea for spontaneously metastatic tumors in clinic.