Exploration of uricase-like activity in Pd@Ir nanosheets and their application in relieving acute gout using self-cascade reaction

Pd@Ir nanosheets exhibit size-dependent uricase-like activity that, in combination with their CAT-like activity, enables an efficient cascade reaction for the effective treatment of acute gout. [Display omitted] Gout, marked by the deposition of sodium urate crystals in joints and peripheral tissues, presents a considerable health challenge. Recent research has shown a growing interest in nanozyme-based treatments for gout. However, literature on nanozymes that combine uricase-like (UOX) activity for uric acid (UA) degradation with catalase (CAT)-like activity for H2O2 elimination through a self-cascade reaction is limited. Herein, we discovered that two-dimensional Pd@Ir nanosheets (NSs) exhibit UOX and CAT activities effectively. Notably, we observed a size-dependent effect of Pd@Ir on activation energy during UA degradation, with the larger Pd@Ir NSs demonstrating a lower energy barrier. The 46-nm Pd@Ir had activation energy as low as 35.9 kJ/mol, surpassing the efficiency of natural bacterial uricase and most reported nanozymes. Through a tandem self-cascade reaction of Pd@Ir, UA was effectively degraded via UOX activity, while the byproduct H2O2 was simultaneously eliminated by CAT-like activity. Cell experiments revealed that Pd@Ir protect normal cells from oxidative stress and promote cell proliferation, demonstrating an excellent self-cascade effect. Additionally, Pd@Ir substantially alleviated gout symptoms in monosodium urate–induced acute gout mice without causing toxic effects on biological organs and tissues. This study opens new avenues for using nanozyme-based cascade reaction systems in the treatment of metabolic diseases.