ABSTRACT Psoriasis is a chronic inflammatory skin disease driven by oxidative stress, necessitating advanced antioxidant nanozymes capable of broad‐spectrum reactive oxygen species (ROS) elimination. Here, we address this challenge through the rational design of a ternary synergistic nanocluster, Ag 14–20 Au 5–11 @FeTP, engineered via “atomic engineering” of an optimal AgAu alloy core and “molecular engineering” via Fe‑porphyrin ligand grafting. This dual‐level engineering creates a metal–ligand synergistic interface that confers excellent multi‐enzyme mimetic activity for scavenging H 2 O 2 , •O 2 − , and •OH. Coupled with enhanced skin penetration, the nanozyme demonstrates both therapeutic and preventive efficacy in a psoriasis mouse model, rivaling the first‐line clinical drug betamethasone/calcipotriol, without observable systemic toxicity. Transcriptomic profiling reveals that its potent effect originates from a dual‐pathway immunomodulation: simultaneous suppression of the pro‐inflammatory IL‑23/Th17/IL‑17 and NF‑κB axes and enhancement of the anti‐inflammatory Treg/Th2 pathways. This work establishes a generalizable “precision synergy” paradigm for designing high‐performance nanocluster‐based therapeutics against oxidative stress‐related inflammatory diseases.
Jiang et al. (Mon,) studied this question.