Department of Chemical Engineering and David H. Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
J Intern Med. 2010 Jan;267(1):9-21. doi: 10.1111/j.1365-2796.2009.02189.x.
RNA interference (RNAi) is a specific gene-silencing mechanism triggered by small interfering RNA (siRNA). The application of RNAi in the clinic requires the development of safe and effective delivery systems. Inspired by progress with lipid-based systems in drug delivery, efforts have been dedicated to the development of liposomal siRNA delivery systems. Many of the lipid-based delivery vehicles self-assemble with siRNA through electrostatic interactions with charged amines, generating multi-lamellar lipoplexes with positively charged lipid bilayers separated from one another by sheets of negatively charged siRNA strands. Internalization of lipid-based siRNA delivery systems into cells typically occurs through endocytosis; accordingly, delivery requires materials that can facilitate endosomal escape. The size of the carrier is important as carriers <100 nm in diameter have been reported to have higher accumulation levels in tumours, hepatocytes and inflamed tissue, whereas larger particles tend to be taken up by Kupffer cells or other components of the reticuloendothelial system (RES). To reduce RES uptake and increase circulation time, carriers have been modified on the surface with hydrophilic materials, such as polyethyleneglycol. Herein, we review the molecular and structural parameters of lipid-based siRNA delivery systems.
RNA 干扰 (RNAi) 是一种由小干扰 RNA (siRNA) 触发的特定基因沉默机制。RNAi 在临床上的应用需要开发安全有效的递送系统。受脂质体药物递送系统进展的启发，人们致力于开发脂质体 siRNA 递送系统。许多基于脂质的递送载体通过与带电荷的胺的静电相互作用与 siRNA 自组装，生成多层层状脂质体复合物，带正电荷的脂质双层彼此分离，由带负电荷的 siRNA 链组成。基于脂质的 siRNA 递送系统进入细胞的内化通常通过内吞作用发生；因此，递送需要能够促进内涵体逃逸的材料。载体的大小很重要，因为据报道，直径 <100nm 的载体在肿瘤、肝细胞和炎症组织中的积累水平更高，而较大的颗粒往往被库普弗细胞或网状内皮系统 (RES) 的其他成分摄取。为了减少 RES 的摄取并增加循环时间，载体的表面已用亲水性材料（如聚乙二醇）进行了修饰。在此，我们综述了基于脂质的 siRNA 递送系统的分子和结构参数。
