A Three‐in‐One Nanoscale Coordination Polymer for Potent Chemo‐Immunotherapy

Abstract The addition of immune checkpoint blockade to standard chemotherapy has changed the standards of care for some cancer patients. However, current chemo‐immunotherapy strategies do not benefit most colorectal cancer patients and many triple‐negative breast cancer patients. Here, the design of a three‐in‐one nanoscale coordination polymer (NCP), OX/GC/CQ, comprising prodrugs of oxaliplatin (OX), gemcitabine (GC), and 5‐carboxy‐8‐hydroxyquinoline (CQ) for triple‐modality chemo‐immunotherapy is reported. OX/GC/CQ exhibits optimal pharmacokinetics and enhanced particle accumulation and drug release in acidic tumor tissues, wherein CQ greatly enhances immunogenic cell death induced by OX/GC and downregulates programmed cell death‐ligand 1 expression in cancer cells. Consequently, OX/GC/CQ efficiently promotes infiltration and activity of cytotoxic T lymphocytes, while decreasing the proportion of immunosuppressive regulatory T cells. Intravenous injection of OX/GC/CQ reduces the growth of colorectal carcinoma and triple‐negative breast cancer, prevents metastasis to lungs, and extends mouse survival by 30–40 days compared to free drugs. This work highlights the potential of NCPs in co‐delivering synergistic chemo‐immunotherapeutics for the treatment of advanced and aggressive cancers.