New cationic polymers for DNA delivery with low toxicity

核酸递送系统对于最先进的疗法的重要性怎么强调都不为过。因此，开发新型的、生物相容的和高效的给药系统对于改善医疗非常重要。传统的人工合成阳离子聚合物(如聚乙烯亚胺)具有较好的转染性，但大多表现出较高的毒性。本论文的目标是制备两种新型的低毒仿生阳离子环状聚合物。在这两种情况下，单一的前体都可以很容易地产生化学和结构不同的聚合物衍生物。此外，这些聚合物将以拓扑和对映体控制的方式制备，这允许进一步调整它们的性能。我们将开发这些功能聚合物作为新型核酸载体，以多链、多链胶束和聚合体的形式存在。然后将评估所有新聚合物的细胞相容性、细胞摄取和在不同模型的前列腺癌细胞中的基因表达。

The importance of nucleic acid delivery systems for state-of-the-art therapeutics can hardly be overstated. Thus, the development of novel, biocompatible and efficient delivery systems is highly important for improved medical treatments. Traditional synthetic cationic polymers employed for transfection (such as polyethyleneimines) show good transfection ability, but they most often exhibit high toxicity. The goal of this thesis project is the preparation of two types of new biomimetic cationic cyclopolymers with low toxicity. In both cases, a single precursor can be used to readily generate chemically and structurally diverse polymer derivatives. Furthermore, these polymers will be prepared in a topologically and enantiomerically controlled fashion, which allows for further tuning of their properties. We will develop these functional polymers as novel nucleic acid carriers in the form of polyplexes, polyplex micelles and polymersomes. All the new polymers will then be evaluated for cellular compatibility, cellular uptake and gene expression in various models of prostate cancer cells.