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Immunotherapies such as immune checkpoint inhibitors are effective in treating several advanced cancers, but these treatments have had limited success in metastatic ovarian cancer. Here we engineered liposomal nanoparticles carrying a poly-ÊŸ-arginine/poly-ÊŸ-glutamate coating that promotes their binding and retention on the surface of ovarian cancer cells. Covalent anchoring of the potent immunostimulatory cytokine interleukin-12 (IL-12) to phospholipid headgroups of the liposome core enabled the polymer-coated particles to concentrate IL-12 in disseminated ovarian cancer tumours following intraperitoneal administration. Shedding of the layer-by-layer coating and serum-protein-mediated extraction of IL-12-conjugated lipids from the liposomal core over time enabled IL-12 to disseminate in the tumour bed following rapid nanoparticle localization in tumour nodules. Optimized IL-12-polymer-coated nanoparticles promoted robust T cell accumulation in ascites and tumours in mouse models, extending survival compared with free IL-12 and sensitizing tumours to immune checkpoint inhibitors, eliciting strong immune responses and immune memory. Overall, these findings support the potential of these polymer-coated nanoparticles for the sustained delivery of IL-12 to disseminated metastatic ovarian cancer.