Integrated ferroptosis, apoptosis, and pyroptosis for liver cancer treatment by an iron single atom-graphene oxide composite

Liver cancer is a widespread and deadly disease without effective treatment. Utilizing the liver's affinity for iron to leverage ferroptosis provides a new direction in treating liver tumors. Herein, we develop an iron single atomgraphene oxide (Fe1-GO) composite as a novel therapeutic agent for liver cancer treatment. Through exogenously introducing iron species and targeting the liver, Fe1-GO promotes ferroptosis and exerts an anti-tumor effect. In vitro experiments demonstrate Fe1-GO's potential to inhibit cell proliferation and induce reactive oxygen species production, triggering apoptosis and pyroptosis, alongside ferroptosis. Key proteins such as ferritin and GPX4, crucial in the regulation of ferroptosis, are found to be downregulated following Fe1-GO treatment. Fe1-GO's effectiveness in reducing tumor size has been confirmed in vivo using a liver cancer model in mice, showcasing its potential as an anti-tumor agent with good biocompatibility. This work paves the way for developing new therapeutic strategies for liver cancer.