Zinc-doped carbon dots from natural Isatis Indigotica folium and calamine: SOD/CAT-mimetic activity targets ROS-Ca²⁺-NLRP3 axis for psoriatic dermatitis therapy

BACKGROUND: Psoriasis is a chronic inflammatory cutaneous disorder characterized by immune dysregulation and aberrant keratinocyte proliferation, necessitating novel effective anti-inflammatory therapies. PURPOSE: This study synthesized zinc-doped carbon dots (IF+Zn-CDs) from Isatis indigotica Folium and calamine, investigating their therapeutic potential and underlying molecular mechanisms in psoriasis treatment. STUDY DESIGN: A bottom-up approach prepared IF+Zn-CDs for systematic physicochemical characterization. Their efficacy was assessed in an IMQ-induced murine psoriasis model, with anti-inflammatory mechanisms explored via transcriptomic and mechanistic assays. METHODS: IF+Zn-CDs were synthesized via bottom-up using the two precursors, characterized by TEM, FTIR, and XPS. An IMQ-induced model evaluated in vivo efficacy; transcriptomic analysis identified modulated pathways, and ROS/intracellular calcium levels clarified NLRP3 regulation, with pyroptosis and MAPK/NF-κB effects validated. RESULTS: The as-synthesized IF+Zn-CDs exhibited a uniform size distribution, excellent dispersibility, high crystallinity, and superior biocompatibility. In the IMQ-induced murine model of psoriasis, IF+Zn-CDs markedly attenuated psoriatic manifestations including erythema, scaling, epidermal hyperplasia, and inflammatory cell infiltration. Transcriptomic analysis revealed that IF+Zn-CDs modulate multiple signaling pathways associated with psoriatic inflammation. Mechanistic investigations confirmed that IF+Zn-CDs inhibit NLRP3 inflammasome activation through the reduction of ROS production and intracellular calcium levels, and further suppress pyroptosis while blocking the MAPK/NF-κB signaling pathway, ultimately ameliorating psoriasiform dermatitis. CONCLUSION: IF+Zn-CDs have potent anti-inflammatory activities and ameliorate psoriasiform dermatitis, highlighting their promising potential as novel anti-inflammatory agents for psoriasis.