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

Abstract Single‐atom nanozymes (SANzymes) emerge as promising alternatives to conventional enzymes. However, chemical instability limits their application. Here, a systematic synthesis of highly active and stable SANzymes is presented 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 heightened catalytic activity of MIrP arises from its robust H₂O₂ adsorption capacity, unique rate‐determining step, and low energy threshold. Crucially, MIrP exhibits remarkable chemical stability under both room temperature and high H₂O₂ concentrations. Further, through modification with (−)‐Epigallocatechin‐3‐Gallate, a natural ligand for Epstein–Barr virus (EBV)‐encoded latent membrane protein 1, targeted SANzyme (MIrPHE) tailored for EBV‐associated nasopharyngeal carcinoma is engineered. 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.