A nanozyme hybrid therapeutic for psoriasis via modulating oxidative-inflammatory cascade

Psoriasis frequently relapses due to a self-amplifying oxidative-inflammatory vicious cycle. Oxidative stress and inflammation mutually promote one another to sustain disease progression, yet conventional single-target therapies often fail to effectively break this pathological cascade. Herein, we develop a novel nanozyme hybrid, pCe@NM, constructed by coating mesoporous ceria nanozymes with a polydopamine interlayer and subsequently fusing them with neutrophil membranes. This system combines multiple antioxidant enzyme-mimetic activities, intrinsic free radical-scavenging capacity, and enhanced colloidal stability, biocompatibility, and inflammation-targeting capability. In H2O2-stimulated macrophages, pCe@NM was efficiently internalized, markedly scavenged intracellular reactive oxygen species, and accordingly reduced the secretion of pro-inflammatory cytokines. Moreover, topical application of pCe@NM to an imiquimod-induced mouse model of psoriasis markedly cleared psoriatic plaques, reduced the Psoriasis Area and Severity Index score, and reversed epidermal hyperplasia. Beyond local repair, pCe@NM rebalanced systemic immunity, evidenced by attenuated splenomegaly and normalized serum levels of pro-inflammatory cytokines. Transcriptomic profiling further revealed that pCe@NM broadly reversed the pathological gene expression program, downregulating genes associated with oxidative stress and inflammatory cascades. Collectively, this nanozyme hybrid therapeutic could disrupt the psoriatic oxidative-inflammatory cascade and restore immune-redox homeostasis, potentially offering an effective platform for the treatment of chronic inflammatory skin disorders.