Comparison of random and gradient amino functionalized poly(2-oxazoline)s: Can the transfection efficiency be tuned by the macromolecular structure?
Comparison of random and gradient amino functionalized poly(2-oxazoline)s: Can the transfection efficiency be tuned by the macromolecular structure?
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DOI：
10.1002/pola.29000
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发表时间：
2018-06-15
影响因子：
--
通讯作者：
Schubert, Ulrich S.
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文献类型：
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作者：
Hertz, David;Leiske, Meike N.;Schubert, Ulrich S.
聚乙烯亚胺可以被认为是体外将DNA递送到细胞中的金标准，但严重的细胞毒性副作用和不适用于体内靶向方法迫切需要设计新的基因载体。由于聚(2-恶唑啉) (P(Ox)) 易于合成和修饰，因此此类聚合物可能是优化聚合物转染过程的理想选择。 2-甲基-2-恶唑啉 (MeOx) 和 2-乙基-2-恶唑啉 (EtOx) 的使用也被认为是有益的，因为这些单体被认为可以克服溶解度问题，介导隐形行为，从而有助于降低细胞毒性。合成了一系列氨基 (AmOx) 官能化 P(Ox) 共聚物与 MeOx（梯度共聚物）或 EtOx（无规共聚物），对其进行脱保护，并对其细胞毒性、复合物形成能力、细胞摄取和转染效率进行生化表征。 AmOx 百分比高于 35 mol% 的聚合物表现出稳定的复合物形成，并且细胞毒性也增加。所有阐明的 P(Ox) 均显示 L929 和 Hepa1-6 细胞系中的转染效率较差。然而，这些研究有助于了解隐形单元（MeOx 和 EtOx）及其在聚合物链内的分布对聚合物复合物选定特性的影响，并描述不同细胞系中氨基官能化 P(Ox) 的特征。 (c) 2018 年 Wiley periodicals, Inc. J. Polym。科学，A 部分：聚合物。化学。 2018, 56, 1210-1224
Poly(ethylene imine) can be considered as the gold standard for DNA delivery into cells in vitro, but severe cytotoxic side-effects and inapplicability for targeted approaches in vivo urgently call for the design of new gene carriers. Since poly(2-oxazoline)s (P(Ox)s) can be easily synthesized and modified, this polymer class might be ideal for the optimization of polymeric transfection processes. The utilization of 2-methyl-2-oxazoline (MeOx) and 2-ethyl-2-oxazoline (EtOx) is also known to be beneficial because these monomers were suggested to overcome solubility issues, mediate stealth behavior and, consequently, facilitate a reduction of cytotoxicity. A series of amino (AmOx) functionalized P(Ox) copolymers with either MeOx (gradient copolymers) or EtOx (random copolymers) was synthesized, deprotected and biochemically characterized regarding cytotoxicity, polyplex formation ability, cellular uptake, and transfection efficiency. Polymers with percentages of AmOx higher than 35 mol % showed stable polyplex formation and also an increase in cytotoxicity. All elucidated P(Ox)s revealed a poor transfection efficiency in both L929 and Hepa1-6 cell lines. However, the investigations contribute to the understanding of the influence of stealth units (MeOx and EtOx) and their distribution within the polymer chain on selected properties of polyplexes and describe characteristics of amino functionalized P(Ox)s in different cell lines. (c) 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1210-1224