Recently, a research team led by Professor WANG Hui from the High Magnetic Field Laboratory, Hefei Institutes of Physical Science (HFIPS), Chinese Academy of Sciences (CAS), in collaboration with the University of Science and Technology of China, the Institute of Health and Medical Technology of HFIPS of CAS, and the University of Macau, successfully developed a coordination-unsaturated copper single-atom nanozyme.
Their findings were published in Advanced Functional Materials.
Malignant tumor treatment remains a major challenge due to the limited precision and significant side effects. Copper-based single-atom nanozymes have shown promise for tumor microenvironment-responsive precision therapy, but their practical application is limited by weak substrate adsorption, difficulty in synthesizing low-coordination unsaturated structures, and limitations of conventional preparation methods.
In this study, the team proposed a ligand chelation conformation strategy. Using EDTA and copper chloride as precursors, they fabricated a carbon dot-supported, coordinatively unsaturated Cu-N2 single-atom nanozyme (Cu-N2-CDs) via a one-step hydrothermal method. For comparison, a coordinatively saturated Cu-N4 nanozyme (Cu-N4-CDs) was also synthesized. The Cu-N2-CDs exhibit dual enzyme-like activities, mimicking both peroxidase and glutathione peroxidase in the tumor microenvironment.
Using the electron paramagnetic resonance spectrometer at the Steady High Magnetic Field Facility, the researchers monitored the in situ generation of hydroxyl radicals (·OH), revealing the structure–activity relationship between the coordination environment of the metal center and key factors such as substrate adsorption, electron transfer efficiency, and therapeutic performance.
Further experimental characterization and density functional theory calculations showed that, compared with conventional Cu-N4 sites, the unsaturated Cu-N2 configuration induces a high-spin, electron-rich state at the metal center. This shifts the d-band center upward, enhances H2O2 adsorption by 3.49 times, increases local electron density, and narrows the band gap, thereby significantly accelerating electron transfer and ·OH generation, with a reaction rate up to 3.62 times higher than that of Cu-N4-CDs.
"Both in vitro and in vivo experiments showed that Cu-N2-CDs have strong anti-tumor effects. They significantly reduced cancer cell viability and performed better than Cu-N4-CDs in cell studies. In animal models, they also achieved much stronger tumor suppression. In addition, the nanozyme enables deep tumor imaging-guided therapy while maintaining good biosafety," said LIN Yefeng, a member of the team.
Schematic diagram of catalytic therapy mechanism of Cu-N2-CDs (Image by LIN Yefeng)
