Ferroptosis Therapy\nof Colorectal Cancer by Single\nCo Atom Supported on Fe-Based Zeolitic Imidazolate Frameworks

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