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. •Biocompatible MnFe2O4 NPs modified with bovine serum albumin were made in one step by chemical co-precipitation method.•The MnFe2O4 NPs exhibit the peroxidase-like and glutathione peroxidase-like function to promote ferroptosis as nanozyme.•The salinomycin and artemisinin generate synergistic anti-tumor effects as a novel strategy.•Effective in-vivo combination chemodynamic therapy.