Fe-Cu Bimetallic Organic Framework Overcomes Antioxidant Barriers to Achieve Synergistic Chemo-Chemodynamic Tumor Therapy

This study overcomes intracellular antioxidant barriers limiting chemodynamic therapy (CDT) by designing an Fe-Cu bimetallic organic framework (MOF) nanocarrier. Synthesized solvothermally, the spindle-shaped MOF (long axis: 3.5 μm; short axis: 2 μm) exhibits a high specific surface area (381.96 m 2 /g) and mesopores (6.69 nm diameter), as verified by SEM/XRD/FT-IR/BET/XPS. The coexisting Fe 3+ /Fe 2+ and Cu 2+ sites enable synergistic catalysis, achieving 68.2 ± 2.1% doxorubicin (DOX) loading with pH-responsive release in tumor-mimetic acidosis (pH 5.4; 78% cumulative release at 72 h, 7.8× higher than neutral pH). In vitro studies confirm dual functions: efficient glutathione depletion (60% absorbance reduction at pH 6.2, 300 μg/mL MOF) and enhanced hydroxyl radical generation via Fenton/Fenton-like reactions (40× TMB absorbance increase). Cell assays demonstrate low cytotoxicity to normal 293T cells within 48 hours (>80% viability at 25 μg/mL) versus potent synergistic efficacy against HeLa cells under simulated tumor microenvironment (100 μM H 2 O 2 ), where chemo-CDT reduces viability to 35% (31.4-37.5% improvement over monotherapies). This work establishes a self-driven platform for tumor-targeted synergistic therapy.