Highly branched poly(β-amino ester)s (HPAEs) have emerged as one type of the most viable non-viral gene delivery vectors, both in vitro and in vivo. However, the effects of different branching strategies on the gene transfection performance have not yet been explored. Here, using triacrylate (B3) and diamine (B4) as the branching monomers, a series of HPAEs were synthesized via the “A2 + B3 + C2” and “A2 + B4 + C2” strategies, respectively. Results show that the branching strategy plays a pivotal role in dictating the physiological properties of the HPAE/DNA polyplexes and thus leads to obviously different cell viability and transfection efficiency. Comparatively, HPAEs synthesized via the “A2 + B3 + C2” branching strategy are more favorable for DNA transfection than that synthesized via the “A2 + B4 + C2” strategy. This study may provide new insights into the development of HPAEs based non-viral DNA delivery system.

在体外和体内，高度分支的聚（β-氨基酯）（HPAE）已经成为最可行的非病毒基因递送载体的一种。但是，尚未探讨不同分支策略对基因转染性能的影响。在此，使用三丙烯酸酯（B3）和二胺（B4）作为支链单体，分别通过“ A2 + B3 + C2”和“ A2 + B4 + C2”策略合成了一系列HPAE 。结果表明，分支策略在决定HPAE / DNA多聚体的生理特性中起着关键作用，从而导致明显不同的细胞活力和转染效率。比较而言，HPAE通过与通过“ A2 + B4 + C2”策略合成的分支策略相比，“ A2 + B3 + C2”分支策略更有利于DNA转染。这项研究可能为基于HPAEs的非病毒DNA递送系统的发展提供新的见解。