Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China Hefei, Anhui, P. R. China.
Small. 2010 Jan;6(2):239-46. doi: 10.1002/smll.200901513.
An efficient and safe delivery system for small interfering RNA (siRNA) is required for clinical application of RNA interfering therapeutics. Polyethyleneimine (PEI)-capped gold nanoparticles (AuNPs) are successfully manufactured using PEI as the reductant and stabilizer, which bind siRNA at an appropriate weight ratio by electrostatic interaction and result in well-dispersed nanoparticles with uniform structure and narrow size distribution. With siRNA binding, PEI-capped AuNPs induce more significant and enhanced reduction in targeted green fluorescent protein expression in MDA-MB-435s cells, though more internalized PEI/siRNA complexes in cells are evidenced by confocal laser scanning microscopy observation and fluorescence-activated cell sorting analyses. PEI-capped AuNPs/siRNA targeting endogenous cell-cycle kinase, an oncogene polo-like kinase 1 (PLK1), display significant gene expression knockdown and induce enhanced cell apoptosis, whereas it is not obvious when the cells are treated with PLK1 siRNA using PEI as the carrier. Without exhibiting cellular toxicity, PEI-capped AuNPs appear to be suitable as a potential carrier for intracellular siRNA delivery.
需要一种高效、安全的小干扰 RNA（siRNA）传递系统，以将 RNA 干扰疗法应用于临床。采用聚乙烯亚胺（PEI）作为还原剂和稳定剂，成功制备了 PEI 封端的金纳米粒子（AuNPs），通过静电相互作用将 siRNA 以适当的重量比结合，得到结构均匀、粒径分布窄的分散良好的纳米粒子。与 siRNA 结合后，PEI 封端的 AuNPs 可诱导 MDA-MB-435s 细胞中靶向绿色荧光蛋白表达的显著增强和增强降低，尽管通过共焦激光扫描显微镜观察和荧光激活细胞分选分析证实细胞内内化的 PEI/siRNA 复合物更多。PEI 封端的 AuNPs/siRNA 靶向细胞周期激酶内源性癌基因 polo 样激酶 1（PLK1），显示出显著的基因表达下调并诱导增强的细胞凋亡，而当使用 PEI 作为载体时，用 PLK1 siRNA 处理细胞时则不明显。PEI 封端的 AuNPs 没有表现出细胞毒性，似乎适合作为细胞内 siRNA 传递的潜在载体。
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