A MXene nanoplatform for psoriasis therapy: Synergistic scavenging of ROS and cfDNA to target inflammation and proliferation.

Psoriasis, a globally prevalent immune-mediated dermatosis, requires novel therapeutic strategies that address its multifactorial pathogenesis, involving oxidative stress, cell-free DNA (cfDNA)-driven inflammation, and keratinocyte hyperproliferation. Here, we presented a pH-responsive two-dimensional (2D) MXene nano-scavenger integrating Ti3C2Tx-mediated antioxidant activity, polyethylenimine (PEI)- facilitated cfDNA scavenging, and 2,3-dimethylmaleic anhydride (DMMA)-induced charge reversal for targeted ATIC inhibitor delivery. Comprehensive material characterization confirmed pH-dependent charge reversal and sustained drug release. In vitro, the MXene-based platform (MPDA) exhibited superior reactive oxygen species (ROS) scavenging (superior to Trolox at the same concentration) and cfDNA adsorption (3-fold higher than pure MXene), while in vivo administration in imiquimod-induced psoriatic mice markedly alleviated disease severity (PASI score reduction of approximately 50%), reduced epidermal thickness (37% decrease compared to the IMQ group), and suppressed inflammatory cytokines-significantly outperforming monotherapies. Transcriptomic analysis further revealed that MPDA cooperatively inhibited multiple inflammatory pathways, including the TNF and IL-17 signaling, thereby effectively disrupting the self-perpetuating inflammatory cycle of psoriasis. This work establishes a promising paradigm for combinatorial nanotherapy in psoriasis treatment.