Zoledronic Acid-Gadolinium Coordination Polymer Nanorods for Improved Tumor Radioimmunotherapy by Synergetically Inducing Immunogenic Cell Death and Reprogramming the Immunosuppressive Microenvironment.

Radiation therapy can potentially elicit a systemic immune response and cause the regression of nonirradiated tumors, and the checkpoint blockade immunotherapies have been introduced to improve their clinical response rate. However, the therapeutic benefits of radioimmunotherapy are still far from satisfactory. Herein, the self-assembled "carrier-free" coordination polymer nanorods are constructed based on gadolinium and zoledronic acid, which can deposit X-ray for improved reactive oxygen species production to induce potent immunogenic cell death (ICD), simultaneously deplete tumor-associated macrophages with regulatory cytokines inhibition, respectively. With the potent ICD induction and reprogrammed immunosuppressive microenvironment, this synergetic strategy can promote antigen presentation, immune priming and T-cell infiltration, and potentiate checkpoint blockade immunotherapies against primary, distant, and metastatic tumors.