Engineering Fe ₃ O ₄ –Fe ₃ C/C heterojunction nanosheets with multimodal therapy for tumor microenvironment-programmed drug delivery and enhanced chemodynamic therapy

Fe₃O₄-iron carbide composites offer promising cancer therapeutic potential <i>via</i> magnetic targeting and tumor-responsive Fe²⁺ release. However, current synthesis methods suffer from complex multi-step procedures, toxic reagents, and poor biocompatibility, necessitating additional surface modifications. Herein, we developed a facile and green strategy to synthesize Fe₃O₄-Fe₃C composites through tannic acid-Fe³⁺ coordination, pyrolysis, and HCl etching. The resulting Fe₃O₄-Fe₃C/C heterojunction composite possesses high saturation magnetization, large specific surface area, and strong Fe-carbon interfacial interactions, which collectively enhance magnetic targeting, drug loading capacity, and Fenton reaction kinetics for amplified chemodynamic therapy. Following polydopamine (PDA) coating and 5-fluorouracil (5-FU) loading, the Fe₃O₄-Fe₃C/C@5-FU@PDA system achieved 55.6% loading efficiency with pH-responsive release (76.1% at pH 5.0 over 48 h). Under 808 nm NIR irradiation (2 W cm^-2, 120 s), the system demonstrated efficient photothermal conversion, elevating tumor temperatures to 45.4 °C for thermal ablation. Both <i>in vitro</i> and <i>in vivo</i> studies confirm superior tumor inhibition <i>via</i> synergistic chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT).