Nanozymes - Tailored Metal-Organic Framework-Based Nanozymes for Enhanced Enzyme-Like Catalysis

The global bacterial infection crisis is exacerbated by the escalating antibiotic resistance of microorganisms. Nanozymes promise to provide an ingenious solution. Here, we report a uniform catalytic architecture, namely platinum (Pt) nanoclusters with finely tuned metal-organic framework (ZIF-8) channel structure, for treating infected wounds. Catalytic site normalization shows that the active sites of the Pt aggregate structure with fine pore modification have a catalytic capacity of 14.903×10^5 min^-1, which is 18.7 times higher than that of Pt particles in a monodisperse state in ZIF-8 (0.793×10^5 min^-1). In situ tests reveal that the change of hydrogen peroxide from homolysis to heterolysis at the nanozyme interface is one of the key reasons for the enhanced activity of the nanozyme. Density functional theory and kinetic simulations of the reaction interface jointly determine the role of the catalytic center and substrate channel. Metabolomics analysis showed that the developed nanozymes, working in synergy with reactive oxygen species, can effectively block the energy metabolism pathway within bacteria, leading to spontaneous apoptosis and bacterial rupture. This groundbreaking study provides new ideas for the regulation of artificial enzyme activity and a new perspective for the development of efficient antibiotic alternatives.

Innovations:
1. A new type of nanozyme combining Pt nanoclusters with ZIF-8 MOF was developed with a finely tuned pore structure.
2. The catalytic ability of the new nanozyme was significantly improved by 18.7 times compared with Pt particles in a monodisperse state.
3. The changes in the hydrogen peroxide cleavage mechanism at the nanozyme interface were revealed, which is the key to improving activity.
4. Metabolomics analysis showed how nanozymes block the bacterial energy metabolism pathway, leading to bacterial apoptosis and rupture.

Inspiration for scientific research:
1. It shows the possibility of improving the performance of nanozymes by customizing MOF structures, providing new ideas for the design of new nanozymes.
2. It emphasizes the importance of in-depth study of the catalytic mechanism, especially the interaction between the catalytic center and the substrate channel, for improving the performance of nanozymes.
3. By integrating density functional theory, kinetic simulation and metabolomics analysis, a multidisciplinary approach is provided for the study of nanozymes.

Idea extension:
1. Clinical application research of nanozymes: Explore the application potential of this new nanozyme in the clinical treatment of infected wounds.
2. Biocompatibility and safety evaluation of nanozymes: Comprehensively evaluate the biocompatibility and safety of nanozymes to ensure their feasibility in medical applications. 3. Large-scale production of nanozymes: Study how to achieve large-scale production of this efficient nanozyme to reduce costs and improve accessibility.
4. Application of nanozymes in the treatment of other diseases: Explore the potential of this nanozyme in the treatment of other diseases caused by drug-resistant bacteria.

5. Smart delivery system of nanozymes: Develop smart delivery systems to improve the targeting and therapeutic effects of nanozymes in vivo.

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