Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
Biomaterials. 2010 May;31(14):4186-93. doi: 10.1016/j.biomaterials.2010.01.110. Epub 2010 Feb 10.
Cationic polymers are widely studied as gene-delivery vehicles, but are limited by low transfection due to inhibited release of DNA, and high cytotoxicity from the requisite positive charges. Here, we introduce a hydrolytic cationic ester polymer containing both tertiary and quaternary amines, which packages DNA into nanoparticles and then releases DNA upon hydrolysis. Cells were transfected with these nanoparticles. Luciferase expression from a polymer with the tertiary/quaternary ratio of 1:1 was equal to that obtained using branched polyethylenimine (PEI), and expression from an acidified polymer with the ratio of 3:1 was 20 times higher than branched PEI. These ratios best balance proton sponging from tertiary amines and packaging ability from cations. Importantly, no hydrolysed polymer exhibited cytotoxicity; the zwitterionic nature of the hydrolysed polymer ensured that the quaternary amines in this work do not cause cell death. Hydrolysis is critical for effective and safe gene therapy.
阳离子聚合物作为基因传递载体被广泛研究，但由于 DNA 释放受到抑制以及所需正电荷导致的高细胞毒性，其转染效率较低。在这里，我们引入了一种含有叔胺和季铵盐的可水解阳离子酯聚合物，它可以将 DNA 包装成纳米颗粒，并在水解时释放 DNA。使用这些纳米颗粒转染细胞后，具有 1:1 的叔胺/季铵比的聚合物的荧光素酶表达与支化聚乙烯亚胺（PEI）相当，而具有 3:1 的比例的酸化聚合物的表达则比支化 PEI 高 20 倍。这些比例可以很好地平衡叔胺的质子海绵效应和阳离子的包装能力。重要的是，没有水解的聚合物表现出细胞毒性；水解聚合物的两性离子性质确保了本工作中的季铵盐不会导致细胞死亡。水解对于有效的和安全的基因治疗至关重要。
