Rinkenauer Alexandra C, Tauhardt Lutz, Wendler Felix, Kempe Kristian, Gottschaldt Michael, Traeger Anja, Schubert Ulrich S
Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany; Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
Macromol Biosci. 2015 Mar;15(3):414-25. doi: 10.1002/mabi.201400334. Epub 2014 Nov 18.
To date, cationic polymers with high transfection efficiencies (TE) often have a high cytotoxicity. By screening an 18-membered library of cationic 2-oxazoline-based polymers, a polymer with similar TE as linear poly(ethylene imine) but no detectable cytotoxicity at the investigated concentrations could be identified. The influence of the polymer side chain hydrophobicity and the type and content of amino groups on the pDNA condensation, the TE, the cytotoxicity, the cellular membrane interaction as well as the size, charge, and stability of the polyplexes was studied. Primary amines and an amine content of at least 40% were required for an efficient TE. While polymers with short side chains were non-toxic up to an amine content of 40%, long hydrophobic side chains induced a high cytotoxicity.
迄今为止，具有高转染效率（TE）的阳离子聚合物通常具有高细胞毒性。通过筛选一个由18种基于2-恶唑啉的阳离子聚合物组成的文库，可以鉴定出一种聚合物，其转染效率与线性聚乙烯亚胺相似，但在所研究的浓度下未检测到细胞毒性。研究了聚合物侧链疏水性、氨基的类型和含量对质粒DNA（pDNA）凝聚、转染效率、细胞毒性、细胞膜相互作用以及多聚体的大小、电荷和稳定性的影响。高效转染效率需要伯胺和至少40%的胺含量。虽然短侧链聚合物在胺含量达到40%时无毒，但长疏水侧链会诱导高细胞毒性。
