biostudies-literaturePires ISHoward Hughes Medical InstituteFoundation for the National Institutes of HealthFoundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)Ragon Institute of MGH, MIT and HarvardNCI NIH HHSMIT | Deshpande Center for Technological Innovation, Massachusetts Institute of Technology322-334https://www.ebi.ac.uk/biostudies/studies/S-EPMC12867765biostudies-literatureUnknown25(2)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-ʟ-arginine/poly-ʟ-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 thNature materialsIL-12-releasing nanoparticles for effective immunotherapy of metastatic ovarian cancer.PMC12867765F99CA274651R01CA235375F99 CA274651P30 CA014051R01 CA235375Nombera Bueno EIrvine DJGomerdinger VFMelo MBCovarrubias GSuh HPickering AJBillingsley MMBacklund CShanker AWu SGordon EPires ISHammond PTPryor MfalseIL-12-releasing nanoparticles for effective immunotherapy of metastatic ovarian cancer.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-ʟ-arginine/poly-ʟ-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 th2026-01-01T00:00:00Z2026 Feb2026-07-15T13:23:02.29Z2026-07-05T03:08:32.51ZS-EPMC128677654117403910.1038/s41563-025-02390-9