The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St Lucia QLD 4072, Australia.
Biomaterials. 2010 Mar;31(7):1821-9. doi: 10.1016/j.biomaterials.2009.10.058. Epub 2009 Nov 17.
Although siRNAs have surpassed expectations in experiments to alter gene expression in vitro, the lack of an efficient in vivo delivery system still remains a challenge in siRNA therapeutics development and has been recognized as a major hurdle for clinical applications. In this paper we describe an inorganic nanoparticle-based delivery system that is readily adaptable for in vivo systems. Layered double hydroxide (LDH) nanoparticles, a family of inorganic crystals, tightly bind, protect, and release siRNA molecules and deliver them efficiently to mammalian cells in vitro. The uptake of siRNA-loaded LDH nanoparticles occurs via endocytosis, whereby the nanoparticles dissolve due to the low pH in the endosome, thereby aiding endosomal escape into the cytoplasm. The influence of LDH nanoparticles on cell viability and proliferation is negligible at concentrations <or=0.050 mg mL(-1), and a pronounced down-regulation of protein expression upon LDH mediated siRNA transfection of HEK293T cells is observed.
尽管 siRNA 在体外改变基因表达的实验中超出了预期，但缺乏有效的体内递送系统仍然是 siRNA 治疗开发的一个挑战，并已被认为是临床应用的主要障碍。在本文中，我们描述了一种基于无机纳米粒子的递药系统，该系统易于适应体内系统。层状双氢氧化物（LDH）纳米粒子是一类无机晶体，可紧密结合、保护和释放 siRNA 分子，并有效地将其递送到体外的哺乳动物细胞中。siRNA 负载的 LDH 纳米粒子通过内吞作用被摄取，其中纳米粒子由于内涵体中的低 pH 值而溶解，从而有助于内涵体逃逸到细胞质中。在浓度<或=0.050mg/mL 时，LDH 纳米粒子对细胞活力和增殖的影响可以忽略不计，并且在 LDH 介导的 HEK293T 细胞的 siRNA 转染后观察到蛋白表达的明显下调。
