Engineering Fe3O4-Fe3C/C Heterojunction Nanosheets with Multimodal Therapy for Tumor Microenvironment-Programmed Drug Delivery and Enhanced Chemodynamic Therapy

Abstract

Fe3O4–iron carbide composites offer promising cancer therapeutic potential via 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/cm2, 120 s), the system demonstrated efficient photothermal conversion, elevating tumor temperatures to 45.4°C for thermal ablation. Both in vitro and in vivo studies confirm superior tumor inhibition via synergistic chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT).