Vuorimaa-Laukkanen Elina, Lisitsyna Ekaterina S, Ketola Tiia-Maaria, Morin-Pickardat Emmanuelle, Liang Huamin, Hanzlíková Martina, Yliperttula Marjo
Laboratory of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere, Finland.
Division of Pharmaceutical Biosciences, Centre for Drug Research, Faculty of Pharmacy, P.O. Box 56, FI-00014, University of Helsinki, Finland.
Eur J Pharm Sci. 2017 May 30;103:122-127. doi: 10.1016/j.ejps.2017.03.025. Epub 2017 Mar 19.
Electrostatic polymer-DNA complexes (polyplexes) have been widely investigated for DNA delivery, and remarkable differences in transfection efficacy have been seen among the materials. For example, polyethyleneimine (PEI) mediates DNA transfection more effectively than poly(l-lysine) (PLL). Biophysical properties of the polyplexes may explain their different properties in gene delivery. We investigated the structural dynamics in DNA polyplexes, especially the material exchange between the core and shell regions of the PEI and PLL polyplexes. Steady-state fluorescence spectroscopy and double labeling based fluorescence resonance energy transfer (FRET) techniques were used to study the DNA polyplexes. According to our results there is a clear difference between these two polymers: core exchange takes place in PEI but not in PLL polyplexes. Such differences in structural dynamics of polyplexes explain, at least partly, the differences in DNA release and transfection efficacy at cellular level.
静电聚合物 - DNA复合物(多聚体)已被广泛研究用于DNA递送,并且在不同材料之间观察到转染效率存在显著差异。例如,聚乙烯亚胺(PEI)介导的DNA转染比聚(L - 赖氨酸)(PLL)更有效。多聚体的生物物理性质可能解释了它们在基因递送中的不同特性。我们研究了DNA多聚体中的结构动力学,特别是PEI和PLL多聚体的核心和外壳区域之间的物质交换。稳态荧光光谱和基于双标记的荧光共振能量转移(FRET)技术被用于研究DNA多聚体。根据我们的结果,这两种聚合物之间存在明显差异:核心交换发生在PEI多聚体中,而在PLL多聚体中则不发生。多聚体结构动力学的这种差异至少部分解释了细胞水平上DNA释放和转染效率的差异。