DNA aptamers target PD-L1 and conjugate gemcitabine as a novel therapeutic strategy α β γ chemotherapy combined with immunotherapy for bladder cancer....

Abstract

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, we have designed and synthesized a novel material PD-L1-GEMs with targeted specificity. PD-L1-GEMs specifically bound to bladder cancer cells. Free gemcitabine cleaved by a phosphatase entered bladder cancer cells through the macropinocytosis pathway and induced cytotoxicity. PD-L1-GEMs showed good stability, binding specificity and significant inhibitory effects in vitro. Two bladder tumor models (subcutaneous model and in-situ model) showed inhibition of growth and progression in PD-L1-GEMs treatment, as well as good biosafety in vivo. The PD-L1 aptamer blocked 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.