Vocelle Daniel, Chesniak Olivia M, Malefyt Amanda P, Comiskey Georgina, Adu-Berchie Kwasi, Smith Milton R, Chan Christina, Walton S Patrick
Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824-1226, USA.
Department of Chemistry, Michigan State University, East Lansing, MI 48824-1226, USA.
Technology (Singap World Sci). 2016 Mar;4(1). doi: 10.1142/S2339547816400100. Epub 2016 Mar 31.
Understanding the endocytosis and intracellular trafficking of short interfering RNA (siRNA) delivery vehicle complexes remains a critical bottleneck in designing siRNA delivery vehicles for highly active RNA interference (RNAi)-based therapeutics. In this study, we show that dextran functionalization of silica nanoparticles enhanced uptake and intracellular delivery of siRNAs in cultured cells. Using pharmacological inhibitors for endocytotic pathways, we determined that our complexes are endocytosed via a previously unreported mechanism for siRNA delivery in which dextran initiates scavenger receptor-mediated endocytosis through a clathrin/caveolin-independent process. Our findings suggest that siRNA delivery efficiency could be enhanced by incorporating dextran into existing delivery platforms to activate scavenger receptor activity across a variety of target cell types.
对于用于基于高效RNA干扰（RNAi）疗法的小干扰RNA（siRNA）递送载体复合物，了解其胞吞作用和细胞内运输仍然是设计siRNA递送载体的关键瓶颈。在本研究中，我们表明二氧化硅纳米颗粒的葡聚糖功能化增强了培养细胞中siRNA的摄取和细胞内递送。使用针对胞吞途径的药理学抑制剂，我们确定我们的复合物通过一种以前未报道的siRNA递送机制被内吞，其中葡聚糖通过网格蛋白/小窝蛋白非依赖性过程启动清道夫受体介导的内吞作用。我们的研究结果表明，通过将葡聚糖纳入现有的递送平台以激活多种靶细胞类型的清道夫受体活性，可以提高siRNA的递送效率。
