New cationic polymers for DNA delivery with low toxicity

核酸递送系统对于最先进的治疗方法的重要性怎么强调都不过分。因此，开发新的、生物相容的和有效的递送系统对于改善医学治疗是非常重要的。用于转染的传统合成阳离子聚合物（如聚乙烯亚胺）显示出良好的转染能力，但它们通常表现出高毒性。本论文的目标是制备两种新型的低毒性仿生阳离子环状聚合物。在这两种情况下，可以使用单一前体来容易地产生化学和结构多样的聚合物衍生物。此外，这些聚合物将以拓扑学和对映体控制的方式制备，这允许进一步调节它们的性质。我们将以复合物、复合物胶束和聚合物囊泡的形式开发这些功能性聚合物作为新型核酸载体。然后，所有新聚合物将在各种前列腺癌细胞模型中进行细胞相容性、细胞摄取和基因表达评估。

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.