Abstract
Due to the poor stability and adverse effects of chemotherapy drugs, such as gemcitabine, the current effectiveness of traditional chemotherapy is minimal. Some patients also show a low response rate to immunotherapy. Therefore, a novel material PD-L1-GEMs is designed and synthesized with targeted specificity. PD-L1-GEMs specifically bind to bladder cancer cells. Free gemcitabine cleaved by a phosphatase enters bladder cancer cells through the macropinocytosis pathway and induces cytotoxicity. PD-L1-GEMs show good stability, binding specificity, and significant inhibitory effects in vitro. Two bladder tumor models (subcutaneous model and in situ model) show inhibition of growth and progression in PD-L1-GEMs treatment, as well as good biosafety in vivo. The PD-L1 aptamer blocks the binding of PD-L1 on the tumor cell surface to PD-1 on T lymphocytes, restoring their immune function, inducing cytokine production and aggregation, and exerting an immune killing role on bladder cancer cells. PD-L1-GEMs represent a successful chemotherapy-immunotherapy strategy for bladder cancer.