Targeting NF-kB signaling with polymeric hybrid micelles that co-deliver siRNA and dexamethasone for arthritis therapy

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• 作者：Qin Wang ; Hao Jiang ; Yan Li ; Wenfei Chen ; Hanmei Li ; Ke Peng ; Zhirong Zhang ; Xun Sun ; ^{sunxun@scu.edu.cn}
• 关键词：NF-kB ; p65 siRNA ; Macrophage polarization ; Arthritis
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：April 2017
• 年：2017
• 卷：122
• 期：Complete
• 页码：10-22
• 全文大小：3700 K
• 卷排序：122

文摘

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.