Gene therapies have become a promising strategy for treating neurological disorders, such as brain cancer and neurodegenerative diseases, with the help of molecular biology interpreting the underlying pathological mechanisms. Successful cellular manipulation against these diseases requires efficient delivery of nucleic acids into brain and further into specific neurons or cancer cells. Compared with viral vectors, non-viral polymeric carriers provide a safer and more flexible way of gene delivery, although suffering from significantly lower transfection efficiency. Researchers have been devoted to solving this defect, which is attributed to the multiple barriers existing for gene therapeutics in vivo, such as systemic degradation, blood–brain barrier, and endosome trapping. This review will be mainly focused on systemically administrated brain-targeted polymers developed so far, including PEI, dendrimers, and synthetic polymers with various functions. We will discuss in detail how they are designed to overcome these barriers and how they efficiently deliver therapeutic nucleic acids into targeted cells.

借助分子生物学解释潜在的病理机制，基因疗法已成为治疗神经系统疾病（如脑癌和神经退行性疾病）的一种有前途的策略。要成功地对这些疾病进行细胞操纵，就需要将核酸有效地传递到大脑中，再进一步传递到特定的神经元或癌细胞中。与病毒载体相比，非病毒聚合物载体提供了更安全，更灵活的基因传递方式，尽管其转染效率大大降低。研究人员致力于解决这一缺陷，这归因于体内基因治疗存在的多种障碍，例如全身性降解，血脑屏障和内体捕获。这项审查将主要集中于到目前为止开发的全身性脑靶向聚合物，包括PEI，树状聚合物和具有各种功能的合成聚合物。我们将详细讨论如何设计它们以克服这些障碍，以及如何有效地将治疗性核酸传递到靶细胞中。