Biscarbamate cross-linked low molecular weight PEI for delivering IL-1 receptor antagonist gene to synoviocytes for arthritis therapy
Biscarbamate cross-linked low molecular weight PEI for delivering IL-1 receptor antagonist gene to synoviocytes for arthritis therapy
复制标题
双氨基甲酸酯交联低分子量 PEI 用于将 IL-1 受体拮抗剂基因递送至滑膜细胞以治疗关节炎
DOI：
10.1016/j.biomaterials.2012.05.044
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发表时间：
2012-09-01
期刊：
影响因子：
14
通讯作者：
Zhang, Xiaoling
中科院分区：
文献类型：
--
作者：
Xiang, Shengnan;Su, Jing;Zhang, Xiaoling
聚乙烯亚胺25 kDa(PEI 25 KDa)是一种广泛报道的用于基因传递的高效转染剂，其细胞毒性是一个关键问题。在我们最近的实验中，小分子量双氨基甲酸酯键交联的聚乙二亚胺(PEI-Bu)(Mn：3278，Mw：4289)可以减少聚阳离子导入诱导的靶细胞凋亡，并且具有与PEI 25 kDa几乎相同的DNA凝聚能力。在将抗炎细胞因子白介素1受体拮抗剂(IL-1ra)基因导入大鼠滑膜细胞方面，培补具有明显高于PEI 25 kDa的活性和较低的细胞毒性，是治疗关节炎的理想靶点。IL-1ra在滑膜细胞中的表达抑制了金属蛋白酶13(MMP13)基因的表达，而MMP13基因参与了IL-1β调控的关节软骨破坏。综上所述，PEI-Bu是一种将IL-1ra基因转移到滑膜细胞治疗关节炎的有前景的工具。(C)2012爱思唯尔有限公司。保留所有权利。
Cytoxicity is an essential concern for polyethyleneimine 25 kDa (PEI 25 kDa), a widely reported, highly effective transfection agent used in gene delivery. In our recent experiments, Small molecular weight cross-linked poly(ethylene imine) by biscarbamate linkage (PEI-Bu) (Mn: 3278, Mw: 4289) can reduce target cell apoptosis induced by polycationic transfection, and has almost the same DNA condensation capability as PEI 25 kDa. PEI-Bu showed significantly higher activity and lower cytotoxicity than PEI 25 kDa in transfecting the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) gene to rat synoviocytes, an optimal target for arthritis treatment. The expression of IL-1Ra in synoviocytes then suppresses the expression of metalloproteases 13 (MMP13) gene, which is responsible for cartilage destruction regulated by IL-1 beta in arthritis. In conclusion, PEI-Bu is a promising tool for delivering IL-1Ra gene to synoviocytes for arthritis therapy. (c) 2012 Elsevier Ltd. All rights reserved.