Work

Bio‐Engineered Fungal‐MOF Nanoplatform Synergizes Macrophage Polarization and Checkpoint Blockade for Potent Melanoma Immunotherapy

Year: 2026

Type: article

Abstract: The clinical efficacy of melanoma immunotherapy is frequently compromised by an immunosuppressive, "cold" tumor microenvironment (TME) driven by redox dysregulation and the metabolic polarization of tumor-associated macrophages (TAMs). To overcome these intertwined barriers, a macrophage-targeted, biomimetic nanoplatform (MOF-808-Ro-G/N) is developed. This system integrates a catalytic metal-organic framework (MOF-808) core loaded with a PERK inhibitor and a CD47 blocking agent, encapsulated within a Rhizopus oryzae (Ro)-derived fungal shell. The biomimetic shell leverages Dectin-1 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-ATF4 metabolic stress axis, reprogramming pro-tumorigenic M2 TAMs toward an anti-tumor M1 phenotype, while concurrently blocking the CD47-SIRPα checkpoint to restore macrophage phagocytosis. Through this orchestrated modulation, MOF-808-Ro-G/N effectively remodels the TME into an immunologically "hot" niche, promoting robust cytotoxic T lymphocyte infiltration and achieving substantial tumor growth suppression. Overall, this "metabolic-immune dual-reprogramming" strategy provides a promising materials-driven paradigm to overcome immunotherapy resistance in solid tumors.

Source: Advanced Healthcare Materials

DOI: 10.1002/adhm.71650