Employing Noble Metal-Porphyrins to Engineer Robust and Highly Active Single-Atom Nanozymes for Targeted Catalytic Therapy in Nasopharyngeal Carcinoma.

Single-atom nanozymes (SANzymes) have emerged as promising alternatives to conventional enzymes. However, the chemical instability limits their application. Here, we present a systematic synthesis of highly active and stable SANzymes by leveraging noble metal-porphyrins. Four noble metal-porphyrins are successfully synthesized to mimic the active site of natural peroxidases through atomic metal-N coordination anchored to the porphyrin center. These noble metal-porphyrins are integrated into a stable and biocompatible Zr-based metal-organic framework (MxP, x denoting Ir, Ru, Pt, and Pd). Among these, MIrP demonstrates superior peroxidase-like activity (685.61 U mg -1 ), catalytic efficiency, and selectivity compared to horseradish peroxidase (267.71 U mg -1 ). Mechanistic investigations unveil that the heightened catalytic activity of MIrP arises from its robust H 2 O 2 adsorption capacity, the unique rate-determining step, and low energy threshold. Crucially, MIrP exhibits remarkable chemical stability under both room temperature and high H 2 O 2 concentrations. Furthermore, through modification with (-)-Epigallocatechin-3-Gallate, a natural ligand for Epstein-Barr virus (EBV)-encoded latent membrane protein 1, we engineer a targeted SANzyme (MIrPHE) tailored for EBV-associated nasopharyngeal carcinoma. This study not only presents an innovative strategy for augmenting the catalytic activity and chemical stability of SANzymes, but also highlights the substantial potential of MIrP as a potent nanomedicine for targeted catalytic tumor therapy. This article is protected by copyright. All rights reserved.