2. Academic Validation
  3. CD4+T cell membrane-based nanocomposites for enhanced dual epigenetic therapy in psoriasis

CD4+T cell membrane-based nanocomposites for enhanced dual epigenetic therapy in psoriasis

  • Acta Biomater. 2025 Jul 1:201:591-603. doi: 10.1016/j.actbio.2025.05.067.
Lin Hou 1,  Ning Wang 2,  Qiannan Miao 2,  Zhihua Wang 2,  Fei Yan 3
Affiliations

Affiliations

  • 1 Department of Dermatology and Venereology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China.
  • 2 State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
  • 3 State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China. Electronic address: feiyan@jlu.edu.cn.
PMID: 40460911 DOI: 10.1016/j.actbio.2025.05.067
Abstract

Psoriasis is an inflammatory skin disease characterized by keratinocyte hyperproliferation and immune cell infiltration. The IL-17 signaling in Th17 cells is crucial in the pathogenesis of psoriasis. Epigenetic regulation could modulate the IL-17 signaling pathway. However, no effective epigenetic drugs can specifically target IL-17 in Th17 cells for psoriasis treatment. Herein, a CD4+T cell biomimetic nanoplatform (HMDC4M) was synthesized for improved dual epigenetic therapy through synergistic suppression of the IL-17 pathway in psoriasis. HMDC4M used hollow mesoporous silica as a framework to load two epigenetic drugs, decitabine and SGCCBP30. HMDC4M exhibited skin absorption capability and selectivity to Th17 cells by coating with CD4+T cell membrane. Moreover, HMDC4M could competitively bind with IL-23, preventing its interaction with CD4+T cells. This inhibited the differentiation of CD4+T cells into Th17 cells and suppressed the production of the inflammatory cytokine IL-17. The cell membrane function of HMDC4M synergized with DNA demethylation and histone deacetylation activities, inhibiting Th17 growth. Finally, the therapeutic effects of HMDC4M were validated in an IMQ-induced psoriasis mouse model. HMDC4M significantly inhibited the PASI score, epidermal thickness, hyperplasia, and splenomegaly. This study provided a proof of concept of biomimetic nanoplatform-based nano epigenetic therapy for inflammatory disease, with great promise to achieve superior clinical outcomes. STATEMENT OF SIGNIFICANCE: 1. A CD4+ T cell biomimetic nanoplatform (HMDC4M) was developed. 2 HMDC4M could competitively bind with IL-23, preventing its interaction with CD4+ T cells. 3 HMDC4M could enhance dual epigenetic therapy for targeting Th17 cells in Psoriasis. 4 HMDC4M significantly inhibited the PASI score, epidermal thickness, hyperplasia, and splenomegaly in an IMQ-induced psoriasis mouse model.

Keywords

CD4(+) T cell; DNA methylation; cell membrane materials; histone acetylation; psoriasis.

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