Pandit Vaibhav, Watson Andre, Ren Liyun, Mixon Amanda, Kotha Shiva P
1 Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York.
2 Ligandal, Inc. , Oakland, California.
Tissue Eng Part C Methods. 2015 Aug;21(8):786-94. doi: 10.1089/ten.TEC.2014.0482. Epub 2015 Apr 28.
Polycationic nanocomplexes are a robust means for achieving nucleic acid condensation and efficient intracellular gene deliveries. To enhance delivery, a multilayered nanoparticle consisting of a core of electrostatically bound elements was used. These included a histone-mimetic peptides, poly-l-arginine and poly-d-glutamic acid was coated with silicate before surface functionalization with poly-l-arginine. Transfection efficiencies and duration of expression were similar when using green fluorescent protein (GFP) plasmid DNA (pDNA) or GFP mRNA. These nanoparticles demonstrated significantly higher (>100%) and significantly longer (15 vs. 4 days) transfection efficiencies in comparison to a commercial transfection agent (Lipofectamine 2000). Reprogramming of human foreskin fibroblasts using mRNA to the Sox2 transcription factor resulted in three-fold higher neurosphere formation in comparison to the commercial reagent. These results demonstrate the potential of these nanoparticles as ideal vectors for gene delivery.
聚阳离子纳米复合物是实现核酸凝聚和高效细胞内基因递送的一种强大手段。为了增强递送效果，使用了一种由静电结合元素核心组成的多层纳米颗粒。这些元素包括一种组蛋白模拟肽、聚-L-精氨酸和聚-D-谷氨酸，在用聚-L-精氨酸进行表面功能化之前，先用硅酸盐进行了包被。使用绿色荧光蛋白（GFP）质粒DNA（pDNA）或GFP mRNA时，转染效率和表达持续时间相似。与市售转染试剂（Lipofectamine 2000）相比，这些纳米颗粒的转染效率显著更高（>100%）且显著更长（分别为15天和4天）。使用mRNA将人包皮成纤维细胞重编程为Sox2转录因子，与市售试剂相比，神经球形成增加了三倍。这些结果证明了这些纳米颗粒作为理想基因递送载体的潜力。
