Department of Biological Sciences and Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
J Control Release. 2011 May 30;152(1):152-8. doi: 10.1016/j.jconrel.2010.12.007. Epub 2010 Dec 24.
Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) was conjugated to the 3' end of small interfering RNA (siRNA) via a disulfide bond to synthesize siRNA-PLGA hybrid conjugates. siRNA-PLGA conjugates were spontaneously self-assembled to form a spherical core/shell type micellar structure of ~20 nm in an aqueous environment, probably by hydrophobic interaction of PLGA blocks in the core surrounded by an siRNA shell layer. When linear polyethylenimine was added to the siRNA-PLGA micelles in aqueous solution, stable siRNA-PLGA/LPEI micelles with a size of ~30 nm were produced via ionic complexation between siRNA and LPEI in the outer shell. The cationic siRNA-PLGA/LPEI micelles showed superior intracellular uptake and enhanced gene silencing effect, compared to naked siRNA/LPEI complexes. The hybrid micelle structure based on siRNA and PLGA can be potentially used as an efficient siRNA delivery system for gene silencing.
可生物降解的聚（D，L-丙交酯-共-乙交酯）（PLGA）通过二硫键连接到小干扰 RNA（siRNA）的 3'端，合成 siRNA-PLGA 杂化物。siRNA-PLGA 杂化物在水溶液中自发自组装形成20nm 的球形核/壳型胶束结构，可能是由核心中 PLGA 嵌段的疏水性相互作用，周围是 siRNA 壳层。当线性聚乙烯亚胺（LPEI）添加到水溶液中的 siRNA-PLGA 胶束中时，通过外壳中 siRNA 和 LPEI 之间的离子络合，生成了尺寸约为30nm 的稳定的 siRNA-PLGA/LPEI 胶束。与裸露的 siRNA/LPEI 复合物相比，阳离子 siRNA-PLGA/LPEI 胶束表现出优异的细胞内摄取和增强的基因沉默效果。基于 siRNA 和 PLGA 的杂合胶束结构可潜在用作用于基因沉默的有效 siRNA 递送系统。
