Urocanic acid-modified chitosan nanoparticles can confer anti-inflammatory effect by delivering CD98 siRNA to macrophages.
Urocanic acid-modified chitosan nanoparticles can confer anti-inflammatory effect by delivering CD98 siRNA to macrophages.
复制标题
尿刊酸修饰的壳聚糖纳米颗粒可以通过将 CD98 siRNA 递送至巨噬细胞来赋予抗炎作用
DOI：
10.1016/j.colsurfb.2016.03.035
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发表时间：
2016-07-01
期刊：
影响因子：
--
通讯作者：
Merlin D
中科院分区：
文献类型：
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作者：
Xiao B;Ma P;Viennois E;Merlin D
CD98在炎症的发生发展中起重要作用。将CD98siRNA(SiCD98siRNA)与尿失碳酸修饰的壳聚糖(UAc)复合形成纳米粒子(NPs)，并将其导入Raw 264.7巨噬细胞，以实现抗炎作用。表征结果表明，与低聚氨基甲胺(OF)和小干扰RNA制备的对照纳米粒相比，所制备的纳米粒具有理想的颗粒尺寸(156.0-247.1 nm)和轻微的正Zeta电位(15.8mV-17.5mV)，并且对Raw 264.7巨噬细胞和结肠-26细胞没有明显的细胞毒性。细胞摄取实验表明，巨噬细胞呈现出时间依赖的UAC/siRNA纳米粒蓄积分布。进一步的体外基因沉默实验表明，重量比为60：1的UAc/siCD98NPs对CD98和促炎细胞因子肿瘤坏死因子-α的抑制效果最好。事实上，用我们的NPs获得的RNAi效率甚至高于/siCD98 NPs的阳性对照。这些结果表明，UAC/siCD98纳米粒可能是治疗炎症性疾病的一种安全、有效和有前途的候选药物。尿囊酸修饰的壳聚糖纳米粒具有抗炎作用，可下调CD98的表达。
CD98 plays an important role in the development and progression of inflammation. Here, CD98 siRNA (siCD98) was complexed with urocanic acid-modified chitosan (UAC) to form nanoparticles (NPs), which were transfected into Raw 264.7 macrophages in an effort to convey anti-inflammatory effects. Characterization showed that the generated NPs had a desirable particle size (156.0–247.1 nm), a slightly positive zeta potential (15.8–17.5 mV), and no apparent cytotoxicity against Raw 264.7 macrophages and colon-26 cells compared to control NPs fabricated by Oligofectamine (OF) and siRNA. Cellular uptake experiments demonstrated that macrophages exhibited a time-dependent accumulation profile of UAC/siRNA NPs. Further in vitro gene silencing experiments revealed that UAC/siCD98 NPs with a weight ratio of 60:1 yielded the most efficient knockdowns of CD98 and the pro-inflammatory cytokine, TNF-α. Indeed, the RNAi efficiency obtained with our NPs was even higher than that of the positive control OF/siCD98 NPs. These results suggest that UAC/siCD98 NPs might be a safe, efficient and promising candidate for the treatment of inflammatory disease. Downregulation of CD98 by urocanic acid-modified chitosan nanoparticles exhibited anti-inflammatory effect.