Ferroptosis Therapy of Colorectal Cancer by Single Co Atom Supported on Fe-Based Zeolitic Imidazolate Frameworks

Ferroptosis therapy has emerged as a promising strategy for cancer treatment due to its unique cell death mechanism and tumor targeting. However, for colorectal cancer (CRC), the tumor cells exhibit ferroptosis resistance, and the reason remains a debate. To enhance the ferroptosis activity for CRC treatment, herein, we loaded a Co single-atom nanozyme on the Fe-based zeolitic imidazolate framework (ZIF) via atomic layer deposition. The synthesized materials performed better anti-HT29 tumor activity in vitro and in vivo than Fe-based ZIFs and showed excellent biosecurity. Based on bioinformatics analysis, Western blot, and immunohistochemical analyses, it was found that the catalyst not only increased the reactive oxygen species by consuming glutathione via the GPX4 pathway but also downregulated the JAK1-STAT3 signal pathway, which benefited to reduce the ferroptosis resistance. This work provides an innovative strategy for CRC treatment and highlights the function of single-atom nanozymes in reducing the ferroptosis resistance.