Nature Materials, Published online: 06 November 2026; doi:10.1038/s41563-026-02774-5A lipid nanoparticle formulation degrades an immunosuppressive receptor on tumour-associated macrophages through its lipids alone, while its messenger RNA cargo reprograms these cells in situ into anti-tumour chimeric antigen receptor macrophages, reshaping the immune microenvironment of malignant ascites in gastrointestinal cancer.