A Dual-Action Microneedle Patch Inhibiting Keratinocyte Ferroptosis and Scavenging Cell-Free DNA for Psoriasis Treatment.

Authors

Jinmin Ye, Wenhao Li, Yatong Qin, Hui Liu, Hehe Xiong, Xiao Wang, Yujie Tian, Fantian Zeng, Weilin Chen, Changrong Shi, Jingxia Zhao, Wei Chen, Zijian Zhou

Published in

Advanced healthcare materials. Pages e71816. Oct 12, 2026. Epub Oct 12, 2026.

Abstract

Psoriasis is a chronic inflammatory skin disorder characterized by dysregulated epithelial-immune interactions. Emerging evidence implicates keratinocyte ferroptosis as a critical pathological mechanism, whereby oxidative epidermal damage and elevated levels of cell-free DNA (cfDNA) amplify immune dysregulation and sustain chronic psoriatic inflammation. Here, we developed a dual-action microneedle system (CAD), with needle tips composed of guanidine-functionalized chitosan and deferoxamine (DFO), designed to eliminate pro-inflammatory cfDNA while locally releasing DFO for iron chelation. In an imiquimod-induced psoriasis mouse model, CAD markedly alleviated psoriatic symptoms, reducing the psoriasis area and severity index score by approximately 50% compared with the model group and demonstrating superior therapeutic efficacy to clinically used calcipotriol. Further studies revealed that CAD depleted accumulated iron and inflammatory cfDNA in lesioned skin, alleviating oxidative stress and suppressing ferroptosis, inhibiting the inflammatory cascade, and maintaining immune homeostasis for effective psoriasis treatment. This study presents a dual-action microneedle therapy for psoriasis that alleviates psoriasis by modulating keratinocyte ferroptosis and scavenging cfDNA to restore inflammatory homeostasis, providing a promising foundation for the development of mechanism-guided combination therapies for psoriasis. Future work will further optimize the formulation for clinical translation and explore its therapeutic potential for other ferroptosis-related inflammatory skin disorders.

PMID:
42864814
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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