Modulating the Coordination Environment of Carbon‐Dot‐Supported Fe Single‐Atom Nanozymes for Enhanced Tumor Therapy

Abstract Herein, carbon dot (CD)‐supported Fe single‐atom nanozymes with high content of pyrrolic N and ultrasmall size (ph‐CDs‐Fe SAzyme) are fabricated by a phenanthroline‐mediated ligand‐assisted strategy. Compared with phenanthroline‐free nanozymes (CDs‐Fe SAzyme), ph‐CDs‐Fe SAzyme exhibit higher peroxidase (POD)‐like activity due to their structure similar to that of ferriporphyrin in natural POD. Aberration‐corrected high‐angle annular dark field scanning transmission electron microscopy (HAADF‐STEM) and X‐ray absorption fine structure spectroscopy (XAFS) analyses show that metal Fe is dispersed in ph‐CDs‐Fe SAzyme as single atoms. Steady‐state kinetic studies show that the maximum velocity ( V max ) and turnover number ( k cat ) of H 2 O 2 homolytic cleavage catalyzed by ph‐CDs‐Fe SAzyme are 3.0 and 6.2 more than those of the reaction catalyzed by CDs‐Fe SAzyme. Density functional theory (DFT) calculations show that the energy barrier of the reaction catalyzed by ph‐CDs‐Fe SAzyme is lower than that catalyzed by CDs‐Fe SAzyme. Antitumor efficacy experiments show that ph‐CDs‐Fe SAzyme can efficiently inhibit the growth of tumor cells both in vitro and in vivo by synergistic chemodynamic and photothermal effects. Here a new paradigm is provided for the development of efficient antitumor therapeutic approaches based on SAzyme with POD‐like activity.