The objective of the present investigation was to design a targeted polyethylenimine (PEI)‐based polyplex by conjugating lactose bearing galactose groups on low molecular weight PEI (LMW PEI) grafted to a high molecular weight PEI (HMW PEI) via a succinic acid linker in order to restore the amine content of the whole conjugate used for ligand conjugation. The PEI conjugate was synthesized and characterized in terms of buffering capacity, particle size, zeta potential, plasmid condensation ability, and protection of DNA against degrading enzymes. Also, the transfection efficiency and cytotoxicity were evaluated in the cell line over‐expressing asialoglycoprotein receptors (ASGPRs) and compared with the cells lacking the receptors. The results demonstrated the ability of PEI conjugate in condensation of plasmid DNA and protection against enzyme degradation. The PEI conjugate formed nanoparticles of around 75 nm with higher buffering capacity compared with unmodified PEI. The polyplexes prepared by the modified PEI could increase the level of transgene up to four folds in the cells over‐expressing the receptor. The results demonstrated the separation of targeting and delivery domains could be considered as a strategy to restore the amine content of the PEI molecule utilized for targeting ligand conjugation.

中文翻译：

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基于半乳糖基化聚乙烯亚胺的靶向双域纳米复合物增强了 IL-12 质粒的递送。

本研究的目的是设计一种基于聚乙烯亚胺（PEI）的靶向复合物，通过在低分子量 PEI（LMW PEI）上通过琥珀酸接头接枝到高分子量 PEI（HMW PEI）上，共轭带有半乳糖基团的乳糖。以恢复用于配体缀合的整个缀合物的胺含量。合成了 PEI 偶联物，并根据缓冲能力、粒径、zeta 电位、质粒凝聚能力和 DNA 对降解酶的保护进行了表征。此外，在过表达去唾液酸糖蛋白受体 (ASGPR) 的细胞系中评估了转染效率和细胞毒性，并与缺乏受体的细胞进行了比较。结果证明了 PEI 缀合物在质粒 DNA 的缩合和防止酶降解方面的能力。与未修饰的 PEI 相比，PEI 缀合物形成了约 75 nm 的纳米颗粒，具有更高的缓冲能力。由修饰的 PEI 制备的复合物可以将过度表达受体的细胞中的转基因水平提高四倍。结果表明，靶向和递送结构域的分离可被视为恢复用于靶向配体缀合的 PEI 分子的胺含量的策略。