Adler Andrew F, Leong Kam W
Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC 27708, USA.
Nano Today. 2010 Dec 1;5(6):553-569. doi: 10.1016/j.nantod.2010.10.007.
Significant effort continues to be exerted toward the improvement of transfection mediated by nonviral vectors. These endeavors are often focused on the design of particulate carriers with properties that encourage efficient accumulation at the membrane surface, particle uptake, and endosomal escape. Despite its demonstrated importance in successful nonviral transfection, relatively little investigation has been done to understand the pressures driving internalized vectors into favorable nondegradative endocytic pathways. Improvements in transfection efficiency have been noted for complexes delivered with a substrate-mediated approach, but the reasons behind such enhancements remain unclear. The phenotypic changes exhibited by cells interacting with nano- and micro-featured substrates offer hints that may explain these effects. This review describes nanoscale particulate and substrate parameters that influence both the uptake of nonviral gene carriers and the endocytic phenotype of interacting cells, and explores the molecular links that may mediate these interactions. Substrate-mediated control of endocytosis represents an exciting new design parameter that will guide the creation of efficient transgene carriers.
为了改进非病毒载体介导的转染，人们仍在付出巨大努力。这些努力通常集中在设计具有促进在膜表面有效积累、颗粒摄取和内体逃逸特性的颗粒载体上。尽管其在成功的非病毒转染中已显示出重要性，但对于驱动内化载体进入有利的非降解性内吞途径的压力，人们的研究相对较少。已注意到采用底物介导方法递送的复合物的转染效率有所提高，但其背后的原因仍不清楚。与纳米和微米特征底物相互作用的细胞所表现出的表型变化提供了可能解释这些效应的线索。本综述描述了影响非病毒基因载体摄取和相互作用细胞内吞表型的纳米级颗粒和底物参数，并探讨了可能介导这些相互作用的分子联系。底物介导的内吞作用控制代表了一个令人兴奋的新设计参数，它将指导高效转基因载体的创建。
