Gold Nanoparticle Size and Shape Effects on Cellular Uptake and Intracellular Distribution of siRNA Nanoconstructs.

Gold Nanoparticle Size and Shape Effects on Cellular Uptake and Intracellular Distribution of siRNA Nanoconstructs.
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DOI:
10.1021/acs.bioconjchem.7b00252
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发表时间:
2017-06-21
影响因子:
4.7
通讯作者:
Odom TW
Odom TW
中科院分区:
化学2区
文献类型:
--
作者:
Yue J;Feliciano TJ;Li W;Lee A;Odom TW

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金纳米粒子(AuNPs)显示出用小干扰RNA(siRNA)干扰靶细胞的潜力,但关键设计参数(如粒子核的大小和形状)的影响是不完整的。本文描述了U87胶质母细胞瘤细胞对基于13 nm球体、50 nm球体和40 nm星形的靶向表达异柠檬酸脱氢酶1(IDH1)的siRNA缀合的金纳米构建体的不同制剂的体外反应的并排比较。与13 nm球体相比,50 nm球体和40 nm星形显示出更高的摄取效率。共聚焦荧光显微镜显示,所有三种制剂在早期孵育时间(2小时)定位在内体中,但在24小时后,50 nm球体和40 nm星形既不在内体中,也不在溶酶体中,而13 nm球体仍留在内体中。透射电子显微镜图像显示,13 nm的球体被封闭和分散内吞囊泡,而50 nm的球体和40 nm的明星聚集,和一些这些纳米颗粒外的内吞囊泡。在我们对不同尺寸和形状的纳米结构进行比较时,在保持SiRNA表面密度和纳米颗粒浓度恒定的情况下,我们发现较大的颗粒(50纳米的球体和40纳米的星状颗粒)作为递送SiRNA的载体表现出更高的潜力。
Gold nanoparticles (AuNPs) show potential for transfecting target cells with small interfering RNA (siRNA), but the influence of key design parameters such as the size and shape of the particle core is incomplete. This paper describes a side-by-side comparison of the in vitro response of U87 glioblastoma cells to different formulations of siRNA-conjugated gold nanoconstructs targeting the expression of isocitrate dehydrogenase 1 (IDH1) based on 13-nm spheres, 50-nm spheres, and 40-nm stars. 50-nm spheres and 40-nm stars showed much higher uptake efficiency compared to 13-nm spheres. Confocal fluorescence microscopy showed that all three formulations were localized in the endosomes at early incubation times (2 h) but that after 24 h, 50-nm spheres and 40-nm stars were neither in endosomes nor lysosomes while 13-nm spheres remained in endosomes. Transmission electron microscopy images revealed that the 13-nm spheres were enclosed and dispersed within endocytic vesicles while 50-nm spheres and 40-nm stars were aggregated, and some of these NPs were outside of endocytic vesicles. In our comparison of nanoconstructs with different sizes and shapes, while holding siRNA surface density and nanoparticle concentration constant, we found that larger particles (50-nm spheres and 40-nm stars) showed higher potential as carriers for the delivery of siRNA.
通过针对溶酶体靶向的金纳米结构来增强人类表皮生长因子受体2在乳腺癌细胞中的降解。
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