siRNA脂质纳米输送载体的研究进展

Lipid-based siRNA Delivery Systems

siRNA能高效且特异地阻断内源性同源基因的表达即RNA干涉(RNAi).RNAi在临床中的应用需要开发安全有效的输送系统,脂质纳米输送载体是一种具有发展潜力的siRNA输送系统.siRNA-脂质复合物的形成主要通过静电相互作用,静电作用必须足够强以至于载体在运输过程中不释放siRNA,而载体到达治疗部位时,解聚释放出siRNA.载体的粒径应小于100 nm,以利于细胞的摄取和透过特定部位的血管开窗.为了减少网状内皮系统(RES)的摄取和延长载体的循环时间,载体的表面由聚乙二醇修饰.本文主要综述了构建siRNA输送载体的基本要求.

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.Efforts have been dedicated to the development of lipid-based systems in siRNA deliveries.Many of the lipid-based delivery vehicles＇ self-assemble with siRNA are through electrostatic interactions with charged amines.Electrostatic interactions must be stable enough to sustain the nucleic payload in the carrier en route,but must allow dissociation,to execute therapeutic activity,at the delivery site.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.To reduce RES uptake and increase circulation time,carriers have been modified on the surface with polyethyleneglycol.Herein,we review basic requirements for building lipid-based siRNA delivery systems.