SGC-CBP30

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.