Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
Biomaterials. 2011 Jul;32(20):4594-603. doi: 10.1016/j.biomaterials.2011.02.065. Epub 2011 Mar 31.
PEGylated cationic polymers have been extensively studied for substituting virus as gene delivery vehicles. These polymers can produce water-soluble polyionic complexes (polyplexes) with plasmid DNA (pDNA) and show enhanced stability compared to non-PEGylated polyplexes. However, PEGylation always diminishes the transfection efficiency of polyplexes probably due to poor cellular internalization of the particles and difficulty in releasing the pDNA cargo from the complexes intracellularly for gene expression. As non-ionic surfactants, Pluronic block copolymers have been shown to interact with plasma membrane and promote cellular uptake of various small molecules and biomacromolecules. To evaluate whether Pluronic could improve the transfection efficiency of polyplexes, Pluronic P85- and PEG-based cationomers comprising poly{N-[N-(2-aminoethyl)-2-aminoethyl] aspartamide (P[Asp(DET)]) cationic blocks were synthesized and tested for their transfection ability. In this study, it was demonstrated that although the stability of the PEG-based polyplexes was better than that of the P85-based polyplexes based cationic polymers, the P85-based polyplex could achieve significantly higher transfection than the PEG counterparts. The improvement of gene delivering ability was shown to be correlated with the enhanced cellular internalization of the P85-based polyplexes.
聚乙二醇化阳离子聚合物已被广泛研究用于替代病毒作为基因传递载体。这些聚合物可以与质粒 DNA（pDNA）产生水溶性聚离子复合物（多聚物），与非聚乙二醇化的多聚物相比，其稳定性更高。然而，聚乙二醇化总是会降低多聚物的转染效率，这可能是由于颗粒的细胞内化能力差以及难以从细胞内的复合物中释放 pDNA 货物以进行基因表达。作为非离子表面活性剂，聚醚嵌段共聚物已被证明可以与质膜相互作用，促进各种小分子和生物大分子的细胞摄取。为了评估 Pluronic 是否可以提高多聚物的转染效率，合成了包含聚{N-[N-(2-氨基乙基)-2-氨基乙基]天冬酰胺（P[Asp(DET)])阳离子嵌段的 Pluronic P85-和基于聚乙二醇的阳离子体，并测试了它们的转染能力。在这项研究中，虽然基于聚乙二醇的多聚物的稳定性优于基于 P85 的多聚物，但基于 P85 的多聚物的转染效率明显高于基于聚乙二醇的多聚物。基因传递能力的提高与基于 P85 的多聚物的细胞内化增强有关。
