Controllable synthesis of variable-sized magnetic nanocrystals self-assembled into porous nanostructures for enhanced cancer chemo-ferroptosis therapy and MR imaging

Abstract

Magnetic-based nanomaterials are promising for cancer diagnosis and treatment. Herein, we develop a self-assembled approach for the preparation of a porous magnetic nanosystem, DOX/Mn(0.25)-Fe₃O₄-III NPs, which can simultaneously achieve chemotherapy, ferroptosis therapy and MRI to improve the therapeutic efficacy. By tuning its porous structures, whole particle sizes and compositions, this nanosystem possesses both a high drug loading capacity and excellent Fenton reaction activity. Owing to the synergetic catalysis effect of iron and manganese ions, the Fenton catalytic activity of Mn(0.25)-Fe₃O₄-III NPs (K_cat = 1.2209 × 10⁻² min⁻¹) was six times higher than that of pure porous Fe₃O₄ NPs (K_cat = 1.9476 × 10⁻³ min⁻¹), making them greatly advantageous in ferroptosis-inducing cancer therapy. Moreover, we found out that these Mn(0.25)-Fe₃O₄-III NPs show a pH-dependent Fenton reaction activity. At acidic tumorous pH, this nanosystem could catalyze H₂O₂ to produce the cytotoxic ˙OH to kill cancer cells, while in neutral physiological conditions it decomposed H₂O₂ into biosafe species (H₂O and O₂). In vivo studies demonstrated that DOX/Mn(0.25)-Fe₃O₄-III NPs exhibited a significant synergistic anticancer effect of combining chemotherapy and ferroptosis therapy and effective T₂-weighted MRI with minimal side effects. Therefore, this porous magnetic nanoplatform has a great potential for combined diagnosis and therapy in future clinical applications.