组会讲课人员:叶龙平
Targeted Dual Small Interfering Ribonucleic Acid Delivery via Non-Viral Polymeric Vectors for Pulmonary Fibrosis Therapy
通过非病毒聚合物载体靶向双小干扰核糖核酸递送用于肺纤维化治疗
主讲人:叶龙平
Adv Mater |February 2021| 2021,33,e200798|DOI: 10.1002/adma.202007798
Abstract:
Inhibiting the myofibroblast differentiation of lung-resident mesenchymal stem cells (LR-MSCs) is a promising yet challenging approach for pulmonary fibrosis (PF) therapy. Here, micelles formed by a graft copolymer of multiple PEGs modified branched polyethylenimine are used for delivering runt-related transcription factor-1 (RUNX1) small interfering RNA (siRNA) (siRUNX1) to the lung, aiming to inhibit the myofibroblast differentiation of LR-MSCs. LR-MSC targeting is
achieved by functionalizing the micelle surface with an anti-stem-cell antigen-1 antibody fragment (Fab′). Consequently, therapeutic benefits are obtained by successful suppression of myofibroblast differentiation of LR-MSCs in bleomycininduced PF model mice treated with siRUNX1-loaded micelles. Furthermore, an excellent synergistic effect of PF therapy is achieved for this micelle system loaded siRUNX1 and glioma-associated oncogene homolog-1 (Gli1) small interfering RNA (siGli1), a traditional anti-PF siRNA of glioma-associated oncogene homolog-1.
Hence, this work not only provides RUNX1 as a novel PF therapeutic target, but also as a promising dual siRNA-loaded nanocarrier system for the therapy of PF.
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摘要:
抑制肺驻留间充质干细胞(LR-MSCs)的肌成纤维细胞分化是一种很有前景但具有挑战性的肺纤维化(PF)治疗方法。在这里,由多个PEG修饰的分支聚乙烯亚胺的接枝共聚物形成的胶束被用于将runt相关转录因子-1(RUNX1)小干扰RNA(siRNA)(siRUNX1)传递到肺,旨在抑制LR-MSCs的肌成纤维细胞分化。LR-MSC靶向是通过用抗干细胞抗原-1抗体片段(Fab‘)功能化胶束表面来实现的。因此,通过用sirunx1胶束处理的睑霉癌诱导的PF模型小鼠,成功抑制LR-MSCs的肌成纤维细胞分化,获得了治疗效果。此外,PF治疗对该胶束系统装载siRUNX1和胶质瘤相关癌基因同源-1(Gli1)小干扰RNA(siGli1)实现了良好的协同效应,这是胶质瘤相关癌基因同源-1的传统抗PFsiRNA。因此,这项工作不仅为RUNX1提供了一种新的PF治疗靶点,而且是一种很有前途的双siRNA负载纳米递送系统。