Inhibition of monocyte adhesion to brain-derived endothelial cells by dual functional RNA chimeras.
Inhibition of monocyte adhesion to brain-derived endothelial cells by dual functional RNA chimeras.
复制标题
DOI：
10.1038/mtna.2014.60
复制
发表时间：
2014-11-04
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
由于白细胞与内皮细胞的粘附是血管-神经元炎症的第一步，因此抑制白细胞与血管内皮细胞的粘附和募集将对神经炎性疾病具有有益作用。本研究利用噬菌体phi 29 DNA包装马达的pRNA构建了一种新型的RNA纳米颗粒，用于特异性靶向小鼠脑源性内皮细胞（bEND 5）上的转铁蛋白受体（TfR），并将ICAM-1 siRNA递送到bEND 5上。该RNA纳米颗粒（FRS-NP）含有靶向TfR的FB 4适体和用于沉默细胞间粘附分子-1（ICAM-1）的siRNA部分。我们的数据表明，这种RNA纳米颗粒被递送到小鼠脑源性内皮细胞中。在TNF-α刺激的细胞和OGD/R条件下，细胞内FRS-NPs释放出siRNA，下调ICAM-1的表达。研究的功能终点表明，FRS-NPs显著抑制TNF-α和OGD/R诱导的单核细胞与bEND 5细胞的粘附。总之，我们使用RNA纳米技术进行siRNA递送的方法可以潜在地应用于抑制缺血性中风和其他神经炎性疾病或影响血管内皮的疾病中的炎症。
Because adhesion of leukocytes to endothelial cells is the first step of vascular-neuronal inflammation, inhibition of adhesion and recruitment of leukocytes to vascular endothelial cells will have a beneficial effect on neuroinflammatory diseases. In this study, we used the pRNA of bacteriophage phi29 DNA packaging motor to construct a novel RNA nanoparticle for specific targeting to transferrin receptor (TfR) on the murine brain-derived endothelial cells (bEND5) to deliver ICAM-1 siRNA. This RNA nanoparticle (FRS-NPs) contained a FB4 aptamer targeting to TfR and a siRNA moiety for silencing the intercellular adhesion molecule-1 (ICAM-1). Our data indicated that this RNA nanoparticle was delivered into murine brain-derived endothelial cells. Furthermore, the siRNA was released from the FRS-NPs in the cells and knocked down ICAM-1 expression in the TNF-α–stimulated cells and in the cells under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. The functional end points of the study indicated that FRS-NPs significantly inhibited monocyte adhesion to the bEND5 cells induced by TNF-α and OGD/R. In conclusion, our approach using RNA nanotechnology for siRNA delivery could be potentially applied for inhibition of inflammation in ischemic stroke and other neuroinflammatory diseases, or diseases affecting endothelium of vasculature.
登录
查看更多内容
影响因子：
3.7
作者：
Bhattacharya, Raktima;Osburg, Berit;Bickel, Ulrich
通讯作者：
Bickel, Ulrich
影响因子：
3.3
作者：
FABRY, Z;WALDSCHMIDT, MM;HART, MN
通讯作者：
HART, MN
影响因子：
3.8
作者：
Boado, Ruben J.;Zhang, Yufeng;Pardridge, William M.
通讯作者：
Pardridge, William M.
影响因子：
4.4
作者：
FROHMAN, EM;FROHMAN, TC;VANDENNOORT, S
通讯作者：
VANDENNOORT, S
影响因子：
8.3
作者：
Ishikawa, M;Cooper, D;Granger, DN
通讯作者：
Granger, DN