The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an M_n ∼ 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60–150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells.

中文翻译：

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多二肽嵌段稳定的复合物用于人类原代细胞的有效转染

多源基因载体的合理设计旨在平衡核酸转染到细胞中的最大功效，同时将不良反应降至最低。M _n的二肽肽嵌段将约5 kDa表现出很强的物理相互作用的物质与PEI部分（2.5或10 kDa）偶联到二嵌段和三嵌段共聚物上。纳米粒子形成并与DNA复合后，与仅使用PEI或脂质复合物相比，所得的复合物（大小通常为60-150 nm）显示出显着的稳定性，并促进了有效的基因传递。通过观察荧光标记的pDNA观察到细胞内运输，并强调了多聚体的有效胞质吸收和DNA向核周间隙的释放。具体而言，具有中间十肽肽嵌段和两个10 kDa PEI燕尾结构的三嵌段共聚物介导了间充质干细胞中具有最高细胞毒性的最高水平的转基因VEGF分泌。这些纳米载体构成了交付平台技术的基础，