Ultrasmall Platinum Nanoclusters Modulating Dysregulated Reactive Oxide Species and Immunity for Psoriasis Therapy and Prevention.

Psoriasis is a chronic inflammatory skin disease that affects millions worldwide. Current treatments are often limited by side effects and high relapse rates. This study introduces an ultrasmall platinum-nanocluster-based artificial enzyme (Pt NE) for effective psoriasis therapy and relapse prevention. Pt NEs exhibit multienzyme mimetic activities─superoxide dismutase, catalase, and glutathione peroxidase-like─with an overall antioxidant capacity 5-fold greater than Au or Cu analogues. Their superior skin penetration (69.93% and 14.27% higher than Au and Cu NEs, respectively) enables efficient reactive oxygen species scavenging and modulation of the inflammatory microenvironment. In vivo, Pt NEs achieve complete psoriatic symptom remission, comparable to a commercial calcipotriol/betamethasone ointment but without steroid-associated adverse effects. Mechanistically, Pt NEs modulate immunity by downregulating pro-inflammatory genes and upregulating genes related to proliferation inhibition and apoptosis. Excellent biocompatibility was observed, with no detectable organ damage or systemic toxicity. This work proposes a safe, effective, and cost-efficient nanotherapeutic strategy with strong potential for clinical translation in psoriasis management.