Microneedle‐Integrated Catalytic Nanosweepers Enable Enrichment‐Driven Clearance of Cell‐Free DNA for Psoriasis Management

ABSTRACT Aberrant extracellular cell‐free DNA (cfDNA) accumulation sustains chronic inflammation in psoriasis by activating the cGAS‐STING pathway and amplifying oxidative stress. However, existing therapies primarily target downstream cytokines and fail to eliminate the upstream nucleic acid trigger. Here, we engineer a microneedle‐integrated catalytic nanosweeper for localized and sustained catalytic cfDNA clearance within psoriatic lesions. The nanosweeper is constructed by embedding polycyanidin‐coated cerium oxide nanozymes (PCeN) into positively charged aminated mesoporous bioactive glass nanoparticles (AMBN), forming an enrichment‐enabled catalytic nanointerface. The AMBN framework electrostatically concentrates cfDNA at the nanoparticle interface and confined PCeN subsequently cleaves the phosphodiester backbone of cfDNA via phosphatase‐like activity while restoring redox homeostasis through superoxide dismutase‐ and catalase‐mimetic functions. This spatially coupled enrichment‐catalysis mechanism converts transient nucleic acid sequestration into sustained catalytic cleavage, effectively disrupting the inflammation‐oxidative stress feedback loop. Integrated into dissolvable microneedles, the platform achieves efficient intradermal delivery and catalytic confinement within hyperkeratotic lesions, resulting in suppression of the cfDNA‐cGAS‐STING axis, immune reprogramming, and epidermal normalization in imiquimod‐induced psoriasis mice. Overall, this study provides a catalytic nanomaterial‐based approach for regulating nucleic acid‐driven inflammation and may offer a potential strategy for the treatment of psoriasis and other cfDNA‐associated inflammatory skin disorders.