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This strategy involves initially activating phagocytic immune cells, such as dendritic cells and macrophages, followed by the reinvigoration of adaptive immune cells, like T cells, to develop effective immune responses against tumors. Herein, the one\u2010two punch strategy is utilized of first activating the innate immune system with biomaterial\u2010based adjuvants composed of succinate polymers and then introducing checkpoint inhibitor anti\u2010PD1 to enhance the adaptive immune response. Specifically, polyethylene succinate nanoparticles (PES NPs) are generated from succinate\u2010based polymers. These nanoparticles induced the activation of mouse\u2010derived dendritic cells and peritoneal macrophages in vitro. When administered intravenously in B16BL6 melanoma tumor\u2010bearing C57BL\/6J mice, PES NPs accumulate and activate macrophages within the tumor microenvironment (TME). Furthermore, infusion of PES NPs and anti\u2010PD1 antibody treatment in B16BL6 tumor\u2010bearing mice resulted in reduced tumor burden. Collectively, these findings suggest that sequential activation of innate and then adaptive immune cells is beneficial for developing cancer immunotherapies.<\/jats:p>","DOI":"10.1002\/smll.202510586","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:27:32Z","timestamp":1763980052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Delivery of Macrophage Activating Nanoparticles and Checkpoint Inhibitors Improves Melanoma Immunotherapy in Mice"],"prefix":"10.1002","volume":"22","author":[{"given":"Madhan Mohan Chandra Sekhar","family":"Jaggarapu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Case Western Reserve University  Cleveland OH 44106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanmoy","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Case Western Reserve 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