Tumor‐targeted and microenvironment‐activatable iron‐based nMOF for synergistic inducing ferroptosis

Ferroptosis is a new form of cell death that relies on iron and involves an imbalance of intracellular reactive oxygen species (ROS), which is expected to help alleviate bottlenecks in tumor treatment. Herein, a sorafenib‐loaded folic acid‐armored iron‐based nMOF was designed for synergistic inducing ferroptosis of tumors. The particle size of the synthesized SM@F is about 210nm, and the drug loading rate is 24.74%. SM@F can be degraded and releases sorafenib and iron ions slowly, resulting in intracellular drug release and iron overload after being highly uptaken by SMMC‐7721 cells. SM@F can effectively inhibit the proliferation of SMMC‐7721 cells, and this effect can be significantly attenuated by ferroptosis inhibitors. Mechanistic investigations revealed that SM@F could increase the content of ROS, and lipid peroxides; decrease the content of glutathione (GSH); and down‐regulate the GXP4 expression in SMMC‐7721 cells. The results indicate that the synthesized SM@F could effectively inhibit the proliferation of tumor cells with synergistic inducing ferroptosis.