Psoriasis is a malignant skin disease characterized as keratinocyte hyperproliferation and aberrant differentiation. Our previous work reported that a bibenzyl compound, erianin, has a potent inhibitory effect on keratinocyte proliferation. To improve its poor water-solubility, increase anti- proliferation activity, and enhance the skin delivery, erianin loaded dendritic mesoporous silica nanospheres (E/DMSNs) were employed. In this work, DMSNs with pore size of 3.5 nm (DMSN1) and 4.6 nm (DMSN2) were fabricated and E/DMSNs showed pore-size-dependent, significantly stronger anti-proliferative and pro-apoptotic effect than free erianin on human immortalized keratinocyte (HaCaT) cells, resulting from higher cellular uptake efficiency. In addition, compared to free erianin, treatment with E/DMSNs was more effective in reducing mitochondrial membrane potential and increasing cytoplasmic calcium levels, which were accompanied by regulation of mitochondria and endoplasmic reticulum stress (ERS) pathway. Porcine skin was utilized in the ex vivo accumulation and permeation studies, and the results indicated higher drug retention and less drug penetration in the skin when administered as the E/DMSNs-loaded hydrogel compared to the erianin-loaded hydrogel. Conlusions This work not only illustrated the further mechanisms of erianin in anti-proliferation of HaCaT cells but also offer a strategy to enhance the efficiency of erianin and the capacity of skin delivery through the DMSNs drug delivery systems.

中文翻译：

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具有促凋亡作用和增强局部递送的负载二安宁的树突状介孔二氧化硅纳米球的开发

牛皮癣是一种恶性皮肤病，其特征在于角质形成细胞过度增殖和异常分化。我们以前的工作报告说，联苄化合物erianin对角质形成细胞的增殖具有有效的抑制作用。为了改善其差的水溶性，增加抗增殖活性并增强皮肤递送，使用了负载有鸟苷的树突状介孔二氧化硅纳米球（E / DMSN）。在这项工作中，制造了孔径分别为3.5 nm（DMSN1）和4.6 nm（DMSN2）的DMSN，并且E / DMSN对人永生化角质形成细胞的孔径依赖性强于其抗增殖和促凋亡作用，其作用远胜于游离erianin。 （HaCaT）细胞，归因于更高的细胞摄取效率。此外，与游离的erianin相比，E / DMSNs的治疗在降低线粒体膜电位和增加细胞质钙水平方面更为有效，同时还伴随着线粒体和内质网应激（ERS）通路的调节。猪皮肤被用于离体积累和渗透研究，结果表明，与负载草酸单宁的水凝胶相比，以负载E / DMSNs的水凝胶给药时，皮肤中的药物保留更高，药物渗透性更低。结论这项工作不仅说明了erianin在HaCaT细胞抗增殖中的进一步机制，而且提供了增强erianin效率和通过DMSNs药物递送系统递送皮肤的能力的策略。伴随着线粒体和内质网应激（ERS）通路的调节。猪皮肤被用于离体积累和渗透研究，结果表明，与负载草酸单宁的水凝胶相比，以负载E / DMSNs的水凝胶给药时，皮肤中的药物保留更高，药物渗透性更低。结论这项工作不仅说明了erianin在HaCaT细胞抗增殖中的进一步机制，而且提供了增强erianin效率和通过DMSNs药物递送系统递送皮肤的能力的策略。伴随着线粒体和内质网应激（ERS）通路的调节。猪皮肤被用于离体积累和渗透研究，结果表明，与负载草酸单宁的水凝胶相比，以负载E / DMSNs的水凝胶给药时，皮肤中的药物保留更高，药物渗透性更低。结论这项工作不仅说明了erianin在HaCaT细胞抗增殖中的进一步机制，而且提供了增强erianin效率和通过DMSNs药物递送系统递送皮肤的能力的策略。并且结果表明，与负载依安宁的水凝胶相比，当以负载E / DMSNs的水凝胶给药时，药物在皮肤中的保留力更高，并且药物在皮肤中的渗透率更低。结论这项工作不仅说明了erianin在HaCaT细胞抗增殖中的进一步机制，而且提供了增强erianin效率和通过DMSNs药物递送系统递送皮肤的能力的策略。并且结果表明，与负载依安宁的水凝胶相比，当以负载E / DMSNs的水凝胶给药时，药物在皮肤中的保留力更高，并且药物在皮肤中的渗透率更低。结论这项工作不仅说明了erianin在HaCaT细胞抗增殖中的进一步机制，而且提供了增强erianin效率和通过DMSNs药物递送系统递送皮肤的能力的策略。