Zhang Qin-Fang, Zhao Rui-Mo, Lei Yu, Tian Xiao-Li, Hu Yue, Zhang Lan, Zhang Ji
College of Chemistry, Sichuan University, Chengdu 610064, PR China.
Biomacromolecules. 2025 Feb 10;26(2):1362-1371. doi: 10.1021/acs.biomac.4c01731. Epub 2025 Jan 29.
Reactive oxygen species (ROS)-sensitive polymers are extensively used in cancer therapies. However, the ROS levels in the tumor microenvironment are often insufficient to trigger an adequate therapeutic response. Herein, we report a cinnamaldehyde ()-based ROS-responsive cationic polymer () and demonstrate its high efficiency in gene delivery and tumor cell growth inhibition. could be released from the polymer via a ROS-sensitive thioacetal bond by endogenous ROS. The released successively induced more ROS accumulation through GSH depletion, and the positive feedback helped to achieve self-accelerating degradation. Results proved that /p53 complexes were efficient in depleting GSH, upregulating ROS levels, and gene transfection. Besides, was also shown to be effective in delivering the therapeutic gene p53. More importantly, /p53 complexes could significantly induce tumor cell growth suppression by a synergistic effect of and p53, providing valuable insights into the design of self-amplifying ROS-responsive polymeric gene vectors.
活性氧（ROS）敏感聚合物在癌症治疗中被广泛应用。然而，肿瘤微环境中的ROS水平往往不足以引发充分的治疗反应。在此，我们报道了一种基于肉桂醛（）的ROS响应性阳离子聚合物（），并证明了其在基因递送和肿瘤细胞生长抑制方面的高效性。可通过内源性ROS经ROS敏感的硫代缩醛键从聚合物中释放出来。释放出的依次通过谷胱甘肽（GSH）耗竭诱导更多的ROS积累，且这种正反馈有助于实现自我加速降解。结果证明/ p53复合物在消耗GSH、上调ROS水平和基因转染方面是有效的。此外，还显示在递送治疗性基因p53方面有效。更重要的是，/ p53复合物可通过和p53的协同作用显著诱导肿瘤细胞生长抑制，为自扩增ROS响应性聚合物基因载体的设计提供了有价值的见解。
