Targeting NF-kB signaling with polymeric hybrid micelles that co-deliver siRNA and dexamethasone for arthritis therapy
Targeting NF-kB signaling with polymeric hybrid micelles that co-deliver siRNA and dexamethasone for arthritis therapy
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使用共同递送 siRNA 和地塞米松的聚合混合胶束靶向 NF-kB 信号传导用于关节炎治疗
DOI：
10.1016/j.biomaterials.2017.01.008
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发表时间：
2017-04-01
期刊：
影响因子：
14
通讯作者：
Sun, Xun
中科院分区：
文献类型：
--
作者：
Wang, Qin;Jiang, Hao;Sun, Xun
转录因子核因子-kB在类风湿关节炎的发病机制中起着关键作用。在这里，我们试图通过使用我们之前开发的聚合物杂交胶束系统共同传递糖皮质激素地塞米松(Dex)和靶向NF-kB p65的小干扰RNA来减缓关节炎的进展。这些胶束包含两种类似的两亲性共聚物：聚己内酯-聚乙烯亚胺(PCL-PEI)和聚己内酯-聚乙二醇酯(PCL-PEI)。负载地塞米松和siRNA的混合胶束比单独含有地塞米松或siRNA的胶束更有效地抑制小鼠巨噬细胞中的核因子-kB信号。此外，联合递送系统能够将巨噬细胞从M1状态切换到M2状态。将含有Dex和siRNA的混合胶束注射到胶原性关节炎小鼠体内，可以使治疗剂在发炎的关节中积聚，减少炎症，而不会损害肾脏或肝脏功能。因此，利用胶束共传递技术阻断炎症组织中核因子-kB的激活，可能为治疗炎症性疾病提供一种新的途径。(C)2017爱思唯尔有限公司。保留所有权利。
The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers: polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing either Dex or siRNA on their own. In addition, the co-delivery system was able to switch macrophages from the M1 to M2 state. Injecting hybrid micelles containing Dex and siRNA into mice with collagen-induced arthritis led the therapeutic agents to accumulate in inflamed joints and reduce inflammation, without damaging renal or liver function. Thus, blocking NF-kB activation in inflammatory tissue using micelle-based co-delivery may provide a new approach for treating inflammatory disease. (C) 2017 Elsevier Ltd. All rights reserved.