Single‐atom catalysts (SACs), as homogeneous catalysts, have been widely explored for chemical catalysis. However, few studies focus on the applications of SACs in enzymatic catalysis. Herein, we report that a zinc‐based zeolitic‐imidazolate‐framework (ZIF‐8)‐derived carbon nanomaterial containing atomically dispersed zinc atoms can serve as a highly efficient single‐atom peroxidase mimic. To reveal its structure–activity relationship, the structural evolution of the single‐atom nanozyme (SAzyme) was systematically investigated. Furthermore, the coordinatively unsaturated active zinc sites and catalytic mechanism of the SAzyme are disclosed using density functional theory (DFT) calculations. The SAzyme, with high therapeutic effect and biosafety, shows great promises for wound antibacterial applications.

Sonodynamic therapy (SDT) can overcome the critical issue of depth-penetration barrier of photo-triggered therapeutic modalities. However, the discovery of sonosensitizers with high sonosensitization efficacy and good stability is still a significant challenge. In this study, the great potential of a metal-organic-framework (MOF)-derived carbon nanostructure that contains porphyrin-like metal centers (PMCS) to act as an excellent sonosensitizer is identified. Excitingly, the superior sonosensitization effect of PMCS is believed to be closely linked to the porphyrin-like macrocycle in MOF-derived nanostructure in comparison to amorphous carbon nanospheres, due to their large highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap for high reactive oxygen species (ROS) production. The nanoparticle-assisted cavitation process, including the visualized formation of the cavitation bubbles and microjets, is also first captured by high-speed camera. High ROS production in PMCS under ultrasound is validated by electron spin resonance and dye measurement, followed by cellular destruction and high tumor inhibition efficiency (85%). This knowledge is important from the perspective of understanding the structure-dependent SDT enhancement of a MOF-derived carbon nanostructure.

Nanozymes have attracted extensive interest owing to their high stability, low cost and easy preparation, especially in the field of cancer therapy. However, the relatively low catalytic activity of nanozymes in the tumor microenvironment (TME) has limited their applications. Herein, we report a novel nanozyme (PtFe@Fe3O4) with dual enzyme‐like activities for highly efficient tumor catalytic therapy. PtFe@Fe3O4 shows the intrinsic photothermal effect as well as photo‐enhanced peroxidase‐like and catalase‐like activities in the acidic TME, thereby effectively killing tumor cells and overcoming the tumor hypoxia. Importantly, a possible photo‐enhanced synergistic catalytic mechanism of PtFe@Fe3O4 was first disclosed. We believe that this work will advance the development of nanozymes in tumor catalytic therapy.

Nanozyme‐based tumor catalytic therapy has attracted widespread attention in recent years. However, its therapeutic outcomes are diminished by many factors in the tumor microenvironment (TME), such as insufficient endogenous hydrogen peroxide (H2O2) concentration, hypoxia, and immunosuppressive microenvironment. Herein, an immunomodulation‐enhanced nanozyme‐based tumor catalytic therapy strategy is first proposed to achieve the synergism between nanozymes and TME regulation. TGF‐β inhibitor (TI)‐loaded PEGylated iron manganese silicate nanoparticles (IMSN) (named as IMSN‐PEG‐TI) are constructed to trigger the therapeutic modality. The results show that IMSN nanozyme exhibits both intrinsic peroxidase‐like and catalase‐like activities under acidic TME, which can decompose H2O2 into hydroxyl radicals (•OH) and oxygen (O2), respectively. Besides, it is demonstrated that both IMSN and TI can regulate the tumor immune microenvironment, resulting in macrophage polarization from M2 to M1, and thus inducing the regeneration of H2O2, which can promote catalytic activities of IMSN nanozyme. The potent antitumor effect of IMSN‐PEG‐TI is proved by in vitro multicellular tumor spheroids (MCTS) and in vivo CT26‐tumor‐bearing mice models. It is believed that the immunomodulation‐enhanced nanozyme‐based tumor treatment strategy is a promising tool to kill cancer cells.

Nanozymesbased tumor catalytic therapy, in which nanozymes specifically trigger enzymatic activity within the tumor sites to produce toxic reactive oxygen species (ROS) for tumor cells killing, represents an emerging antitumor modality. [3] In recent years, various nanozymes such as metal oxides, noble metals, metal-organic frameworks, and single-atom nanozymes (SAzymes) are explored as diverse enzyme mimics for tumor therapy. [1a,4] Among them, SAzymes are very promising antitumor agents due to their tunable electronic and geometric structures, maximum atomic utilization efficiency, and excellent catalytic activities. [5] The greatest advantage of SAzymes is that their active sites can be directly designed similar to those of natural enzymes, [6] thus allowing SAzymes to exhibit the catalytic behaviors closer to those of natural enzymes, as well as helping to unravel the action mechanisms of nanozymes involved in tumor catalytic therapy. Despite some breakthroughs in this field, it remains a great challenge to precisely optimize the local coordination structures of SAzymes for more efficient enzyme-like catalysis and tumor therapeutic outcome.In many biological application scenarios, the structure and function of enzymes provide important guidance for the rational design of nanozymes. Horseradish peroxidase (HRP), Single-atom nanozymes (SAzymes) represent a new research frontier in the biomedical fields. The rational design and controllable synthesis of SAzymes with well-defined electronic and geometric structures are essential for maximizing their enzyme-like catalytic activity and therapeutic efficacy but remain challenging. Here, a melamine-mediated pyrolysis activation strategy is reported for the controllable fabrication of iron-based SAzyme containing five-coordinated structure (FeN 5 ), identified by transmission electron microscopy imaging and X-ray absorption fine structure analyses. The FeN 5 SAzyme exhibits superior peroxidase-like activity owing to the optimized coordination structure, and the corresponding catalytic efficiency of Fe-species in the FeN 5 SAzyme is 7.64 and 3.45 × 10 5 times higher than those in traditional FeN 4 SAzyme and Fe 3 O 4 nanozyme, respectively, demonstrated by steadystate kinetic assay. In addition, the catalytic mechanism is jointly disclosed by experimental results and density functional theory studies. The as-synthesized FeN 5 SAzyme demonstrates significantly enhanced antitumor effect in vitro and in vivo due to the excellent peroxidase-like activity under tumor microenvironment.