Given the various cationic polymers developed as non-viral gene delivery vectors, polyethylenimine (PEI) has been/is frequently used in in vitro transfection. However, the primary drawback limiting its in vivo applications is the sharp decrease in transfection efficiency in the presence of serum. Here, we investigated the influences of serum proteins or bovine serum albumin (BSA) on the physicochemical properties of PEI/DNA complexes (polyplexes), including hydrodynamic diameters and agglomeration behavior, zeta potentials, morphologies, and sensitivity to the presence of salt. Mechanism studies revealed that the protein corona determined the endocytic rates and pathways, intracellular transport, the rate of endo/lysosomal trafficking, vesicle escape efficiency, and thus the overall gene expression levels. This work offers mechanistic insights for the serum-induced suppression of transfection efficiency, which is the reduced endo/lysosomal escape of the protein-coated polyplexes, in contrast to the protein free polyplexes.

中文翻译：

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关于蛋白质电晕如何调节聚乙烯亚胺（PEI）复合物的理化特性和基因传递的详细研究†

考虑到各种阳离子聚合物被开发为非病毒基因递送载体，聚乙烯亚胺（PEI）已经/经常用于体外转染。但是，其主要缺点是限制了它的体内活性应用是在血清存在下转染效率急剧下降。在这里，我们调查了血清蛋白或牛血清白蛋白（BSA）对PEI / DNA复合物（多复合物）的理化性质的影响，包括流体动力学直径和团聚行为，ζ电位，形态以及对盐存在的敏感性。机制研究表明，电晕蛋白决定了内吞率和通路，细胞内转运，内/溶酶体转运率，囊泡逃逸效率，从而决定了整体基因表达水平。这项工作为血清诱导的转染效率抑制提供了机械方面的见解，与无蛋白复合物相比，这种作用减少了蛋白包被复合物的内/溶酶体逸出。