Artemisinin and salinomycin co-loaded nanozymes to boost cascade ROS accumulation for augmented tumor ferroptosis

Ferroptosis, which depends on iron ions to generate reactive oxygen species (ROS), has been proved to be an effective strategy for cancer therapy. However, cells will initiate different programs, including reducing iron uptake and storing excess iron in ferritin, to lower the intracellular iron concentration. In this work, we reported a simple, one-pot method to synthesize bovine serum albumin stabilized MnFe₂O₄ nanoparticles (MnFe₂O₄@BSA NPs) for ferroptosis therapy of cancer. Artemisinin (ART) and salinomycin (Sali), which could induce the degradation of ferritin and enhance the uptake by increasing binding protein IRP2 and transferrin receptor, were loaded onto the MnFe₂O₄@BSA NPs to strengthen the killing effect. The prepared MnFe₂O₄@BSA-ART/Sali (MnFe₂O₄/ART/Sali) NPs could significantly increase the cellular iron concertation, enhancing the ROS generation in cells. After intravenous injection, the MnFe₂O₄/ART/Sali NPs showed superior anti-tumor effects, with a tumor inhibition rate of 67.65 %. Hence, the hybrid nanocomposite indicated the combined effect of MnFe₂O₄, ART, and Sali, providing a platform to enhance ferroptosis therapy of cancer.