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The immunomodulatory efficacy of current psoriasis biological therapies is hindered by their limited ability to scavenge multiple cytokines, inefficient delivery to specific inflamed skin regions, and potential side effects. Upon analyzing samples from both patients and mice, we identify a significant increase in type IV collagen within the extracellular matrix (ECM) of psoriatic skin. Thus, we report the microneedle (MN) delivery of type IV collagen targeting peptide-modified dual-cell membrane biomimetic nanodecoys (CRHM@lip) with multiple cytokines scavenging ability for treating psoriasis. The CRHM@lip can scavenge both tumor necrosis factor-α (TNF-α) and interleukin (IL)-17. Upon MN delivery, the nanodecoys target ECM and exhibit skin retention for over 120 h. The treatment by CRHM@lip-integrated MNs reduces skin thickness in mice by 57.9% and shows decreased levels of TNF-α, IL-17, IL-23, and interferon (IFN)-γ in skin sections compared to the psoriasis group. Additionally, the CRHM@lip treatment reduces the CD4+ T cells, M1 macrophages, and dendritic cells in the spleen, and suppresses various inflammatory mediators in serum, significantly demonstrating immunological microenvironmental suppression. Compared to systemic administration routes, MN delivery improves treatment outcomes. No noticeable adverse effects on hepatic and renal functions are observed in mice after treatment. This approach enhances the effectiveness of biological therapies and has the potential for translation.
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