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

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 x 10(-2) min(-1)) was six times higher than that of pure porous Fe3O4 NPs (K-cat = 1.9476 x 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 O-2). 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 T-2-weighted MRI with minimal side effects. Therefore, this porous magnetic nanoplatform has a great potential for combined diagnosis and therapy in future clinical applications.