The Power of Shielding: Low Toxicity and High Transfection Performance of Cationic Graft Copolymers Containing Poly(2-oxazoline) Side Chains,Biomacromolecules

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The Power of Shielding: Low Toxicity and High Transfection Performance of Cationic Graft Copolymers Containing Poly(2-oxazoline) Side Chains
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-05-23 00:00:00 , DOI: 10.1021/acs.biomac.8b00362
Anne-Kristin Trützschler _{1,

2} , Tanja Bus _{1,

2} , Martin Sahn _{1,

2} , Anja Traeger _{1,

2} , Christine Weber _{1,

2} , Ulrich S. Schubert _{1,

2}

Affiliation

We show the potential of oligo(2-ethyl-2-oxazoline) (Ox_n)-shielded graft copolymers of (2-aminoethyl)-methacrylate and N-methyl-(2-aminoethyl)-methacrylate for pDNA delivery in HEK cells. For the effect of grafting density and side chain length concerning improved transfection properties through the concept of shielding to be investigated, copolymers were synthesized via the macromonomer method using a combination of cationic ring opening polymerization and reversible addition–fragmentation chain transfer polymerization to vary the degree of grafting (DG = 10 and 30%) as well as the side chain degree of polymerization (DP = 5 and 20). Investigations of the polyplex formation, in vitro flow cytometry, and confocal laser scanning microscopy measurements on the copolymer library revealed classical shielding properties of the Ox side chains, including highly reduced cytotoxicity and a partial decrease in transfection efficiency, as also reported for polyethylene glycol shielding. In terms of the transfection efficiency, the best performing copolymers (A-g-Ox₅(10) and M-g-Ox₅(10)) revealed equal or better performances compared to those of the corresponding homopolymers. In particular, the graft copolymers with low DG and side chain DP transfected well with over 10-fold higher IC₅₀ values. In contrast, a DG of 30% resulted in a loss of transfection efficiency due to missing ability for endosomal release, and a side chain DP of 20 hampered the cellular uptake.

中文翻译：

屏蔽的力量：含聚（2-恶唑啉）侧链的阳离子接枝共聚物的低毒性和高转染性能

我们显示了（2-氨基乙基）-甲基丙烯酸酯和N的低聚（2-乙基-2-恶唑啉）（Ox _n）保护的接枝共聚物的潜力-甲基-（2-氨基乙基）-甲基丙烯酸酯用于在HEK细胞中传递pDNA。为了通过接枝的概念研究接枝密度和侧链长度对改善转染性能的影响，采用阳离子开环聚合和可逆加成-断裂链转移聚合相结合的大单体方法合成共聚物接枝率（DG = 10和30％）以及侧链聚合度（DP = 5和20）。对共聚物库中多链体形成，体外流式细胞术和共聚焦激光扫描显微镜测量的研究表明，Ox侧链具有经典的屏蔽特性，包括细胞毒性大大降低，转染效率部分降低，也报道了聚乙二醇的屏蔽作用。就转染效率而言，性能最好的共聚物（与相应的均聚物相比，A- g - Ox ₅（10）和M- g- Ox ₅（10）表现出相同或更好的性能。特别是，低DG和侧链DP的接枝共聚物转染效果良好，IC ₅₀值提高了10倍以上。相反，由于缺少内体释放能力，DG的30％导致转染效率的损失，而侧链DP的20阻碍了细胞的吸收。

更新日期：2018-05-23

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