Targeting PD-L1 with DNA Aptamers and Conjugated with Gemcitabine as a Novel Therapeutic Strategy for Bladder Cancer Chemotherapy Combined with Immunotherapy.

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.