A polysaccharide-based hydrogel integrated with nanozyme activity for synergistic photothermal-enzymatic therapy of psoriasis.

Psoriasis is a chronic inflammatory skin disorder driven by intertwined pathogenic factors, including microbial infection, oxidative stress, and immune dysregulation, which necessitates combinatory therapeutic strategies. Here, we engineered a carboxymethyl chitosan (CMCS)-based ternary hydrogel (FP) by synergistically incorporating sodium alginate (SA) and polyacrylamide (PAAm) to host polypyrrole (PPy)-coated magnetite nanozymes (Fe₃O₄@PPy). The resulting composite hydrogel integrates exogenous photothermal conversion and peroxidase-mimicking activities with the inherent antioxidant capacity of the CMCS-SA network, conferring a triple therapeutic modality-antibacterial, anti-inflammatory, and antioxidative. The FP hydrogel exhibited excellent colloidal stability and potent near-infrared (NIR)-triggered antibacterial activity, achieving >99% killing efficacy against bacteria. In an imiquimod-induced psoriasis mouse model, FP hydrogel combined with NIR irradiation significantly alleviated psoriatic symptoms, reducing the Psoriasis Area Severity Index (PASI) score from 8.67 ± 0.76 (model group) to 2.83 ± 0.58 (p < 0.001). Histological analysis confirmed marked reductions in epidermal thickness and inflammatory cell infiltration, accompanied by downregulated expression of key pro-inflammatory cytokines (IL-17A and TNF-α). This orchestrated synergy among the macromolecular scaffold and functional nanozymes positions the FP hydrogel as a promising candidate for effective, multi-mechanistic psoriasis management, offering a chemical-drug-free strategy to enhance patients' quality of life.