银屑病是一种伴随慢性丘疹鳞屑病变和多种共病的炎症性皮肤疾病，严重影响患者的生活质量。为了开发银屑病的改进治疗策略，利用介孔二氧化硅纳米粒子（MSNs）作为纳米载体，将一种具有高抗炎活性的多甲氧基黄酮（PMFs）类物质5-去甲基川丹素（5-DN）分别在体外和体内用于人体角质形成细胞HaCaT细胞系和银屑病类病变小鼠模型。药物载体系统（MSNs@5-DN）显著提高了5-DN的生物相容性和生物可利用性。细胞生物学、组织病理学和分子水平的研究揭示了药物递送系统的药理机制，包括通过下调肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）的前炎症因子水平来抑制炎症反应。还观察到上调了抗炎细胞因子转化生长因子-β1（TGF-β1）和miR-17-5p（PTEN/AKT通路的关键调节因子）。小鼠模型中用MSNs@5-DN进行治疗可显著改善银屑病样病变。与游离的5-DN相比，设计的药物载荷系统在治疗银屑病样病变方面显示出更强的治疗效果。该研究揭示了功能化MSNs负载PMFs在人类银屑病临床治疗中的协同作用。© 2023 Elsevier B.V. 发布

Psoriasis is an inflammatory skin disease accompanied with chronic papulosquamous lesions and multiple comorbidities that considerably affect patients' quality of life. In order to develop an enhanced therapeutic strategy for psoriasis, 5-demethylnobiletin (5-DN), a kind of polymethoxyflavones (PMFs) with high anti-inflammatory activity, was delivered in vitro and in vivo by the nanocarrier of mesoporous silica nanoparticles (MSNs) both in the human keratinocytes HaCaT cell line and the mouse model with psoriasis-like lesions. The drug-loaded nanocarrier system (MSNs@5-DN) significantly improved the biocompatibility and bioavailability of 5-DN. Investigations at cell biological, histopathological, and molecular levels revealed the pharmacological mechanism of the drug delivery system, including the inhibition of inflammatory responses by downregulating the proinflammatory cytokine levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). The upregulation of anti‑inflammatory cytokine of transforming growth factor-β1 (TGF-β1) and microRNA-17-5p, a critical regulator of the PTEN/AKT pathway, was also observed. The psoriasis-like lesions were markedly ameliorated in the mouse models treated with MSNs@5-DN. The designed drug-loading system shows an enhanced therapeutic outcome for psoriasis-like lesion compared with free 5-DN. This study revealed the synergistic effect of functionalized MSNs loaded with PMFs on the clinical treatment of human psoriasis.Copyright © 2023. Published by Elsevier B.V.