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

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.

Automated summary

The design of a three-in-one nanoscale coordination polymer (NCP), OX/GC/CQ, combining oxaliplatin (OX), gemcitabine (GC), and 5-carboxy-8-hydroxyquinoline (CQ) prodrugs, promotes triple-modality chemo-immunotherapy. OX/GC/CQ exhibits optimal pharmacokinetics, enhanced particle accumulation and drug release in acidic tumor tissues. It efficiently promotes infiltration and activity of cytotoxic T lymphocytes, while decreasing immunosuppressive regulatory T cells, leading to the suppression of tumor growth and metastasis.