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To overcome these intertwined barriers, a macrophage\u2010targeted, biomimetic nanoplatform (MOF\u2010808\u2010Ro\u2010G\/N) is developed. This system integrates a catalytic metal\u2013organic framework (MOF\u2010808) core loaded with a PERK inhibitor and a CD47 blocking agent, encapsulated within a\n                    <jats:italic>Rhizopus oryzae<\/jats:italic>\n                    (Ro)\u2010derived fungal shell. The biomimetic shell leverages Dectin\u20101 interactions to enable precise TAM targeting and accumulation. Upon endocytosis, the acidic endosomal microenvironment activates the MOF core to deplete glutathione and trigger a surge of reactive oxygen species, thereby inducing immunogenic cell death. Synergistically, the released payloads disrupt the PERK\u2010ATF4 metabolic stress axis, reprogramming pro\u2010tumorigenic M2 TAMs toward an anti\u2010tumor M1 phenotype, while concurrently blocking the CD47\u2010SIRP\u03b1 checkpoint to restore macrophage phagocytosis. Through this orchestrated modulation, MOF\u2010808\u2010Ro\u2010G\/N effectively remodels the TME into an immunologically \u201chot\u201d niche, promoting robust cytotoxic T lymphocyte infiltration and achieving substantial tumor growth suppression. Overall, this \u201cmetabolic\u2013immune dual\u2010reprogramming\u201d strategy provides a promising materials\u2010driven paradigm to overcome immunotherapy resistance in solid tumors.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71650","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:24:31Z","timestamp":1787804671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bio\u2010Engineered Fungal\u2010MOF Nanoplatform Synergizes Macrophage Polarization and Checkpoint Blockade for Potent Melanoma Immunotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiaolong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy Ningxia Medical University  Yinchuan P. R. 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