Boosting ferroptosis therapy by sorafenib and ML385 loaded CuFe₂O₄ nanozymes

Ferroptosis as a promising therapeutic modality has been widely employed in cancer treatment. However, low efficacy of Fenton reaction and the presence of antioxidants, including glutathione (GSH) and glutathione peroxidase 4 (GPX4), weaken the ferroptosis anticancer effects. In this study, we synthesized copper ferrite (CuFe₂O₄) nanozymes loaded with sorafenib and ML385 to boost ROS generation and improve the ferroptosis effects. The CuFe₂O₄ nanozymes exhibited superior Fenton reaction catalytic activities due to the coexistence of iron and copper ions. While, sorafenib and ML385 inhibited the antioxidant effect by impeding the synthesis of GSH and the expression of NRF2, respectively. To prevent the CuFe₂O₄ nanozymes from being quickly cleared by the reticuloendothelial system (RES), the nanozymes were further coated with the macrophage membrane. What's more, the CuFe₂O₄ also demonstrated excellent photothermal effect. This nanoplatform exhibited superior tumor therapeutic efficacy due to its exceptional GSH depletion ability, high ROS generation efficiency, and excellent photothermal therapy (PTT) effect, presenting considerable potential for cancer treatment.