131I-?PD-L1 immobilized by bacterial cellulose for enhanced radio-immunotherapy of cancer

Radioisotope therapy (RIT) of cancer is restrained by the nonspecific distribution of radioisotope and ineptitude for metastatic tumors. Meanwhile, the clinical application of immune checkpoint blockade (ICB) confronts problems such as low responsive rate, multiple administration requirements and immune-related adverse events (irAE). To address these challenges, we prepared an injectable suspension by immobilizing 131I-labeled antiprogrammed cell death-ligand 1 antibody (alpha PD-L1) in bacterial cellulose for precise and durable radioimmunotherapy of cancer. The crisscross network structure of bacterial cellulose nanofibers would contribute to the long-term retention of 131I-labeled alpha PD-L1 within tumors, which could reduce the side effect stemmed from the nonspecific 131I distribution in normal tissues. The potent long-term RIT of 131I, combined with ICB by alpha PD-L1, could effectively restrain the growth of primary tumor in mice. In addition to the direct killing effect, 131I-alpha PD-L1 immobilized by bacterial cellulose could enhance the immunogenic cell death (ICD) of cancer cells, activating the maturation of multiple immune cells to induce a systemic anti-tumor immune effect. Our therapeutic strategy could suppress spontaneous cancer metastasis and prolong the survival time of tumor-bearing mice. This study proposed a new approach for combined radio-immunotherapy and a novel solution for tumor metastasis in advanced-stage cancers.