A smart hydrogel integrating nanozyme-mediated ROS clearance and microenvironment-activated H 2 S release for precise psoriasis therapy

Abstract Psoriasis is a prevalent chronic immune-mediated skin disease characterized by excessive reactive oxygen species (ROS), immune imbalance, and inflammatory infiltration. Traditional single-target therapies often fail to achieve long-term remission. Here, we developed a multifunctional injectable hydrogel (JK&CM@HG) that integrated nanozyme-mediated antioxidant activity with hydrogen sulfide (H2S) gas therapy for effective psoriasis treatment. The hydrogel exhibited good inject ability and tissue adhesion. Cerium-based metal-organic framework (Ce-MOF) nanozyme (CM) mimicked superoxide dismutase (SOD) and catalase (CAT), and scavenged superoxide anions (O2·−) and hydrogen peroxide (H2O2) to reduce oxidative stress. Meanwhile, the H2S donor JK-1 (JK) releases H2S in response to the acidic microenvironment, promoting macrophage polarization from M1 to M2, enhancing angiogenesis, and inhibiting abnormal keratinocyte proliferation. In vivo results showed that the hydrogel markedly alleviates erythema, reduces epidermal thickness, and restores near-normal architecture. Overall, JK&CM@HG achieved multi-target microenvironment modulation through synergistic ROS scavenging and H2S therapy, effectively suppressing inflammation and promoting repair, offering a promising materials-design strategy for psoriasis management.