基于肉桂醛的ros反应聚合基因载体的高效基因传递和肿瘤细胞生长抑制。

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2025-02-10 Epub Date: 2025-01-29 DOI:10.1021/acs.biomac.4c01731

Qin-Fang Zhang, Rui-Mo Zhao, Yu Lei, Xiao-Li Tian, Yue Hu, Lan Zhang, Ji Zhang

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引用次数: 0

摘要

活性氧（ROS）敏感聚合物广泛应用于癌症治疗。然而，肿瘤微环境中的ROS水平往往不足以引发足够的治疗反应。本文报道了一种基于肉桂醛（CA）的ros响应阳离子聚合物（PCA），并证明其具有高效的基因传递和肿瘤细胞生长抑制作用。CA可以通过内源性ROS通过对ROS敏感的硫缩醛键从聚合物中释放出来。释放的CA通过GSH耗竭诱导更多的ROS积累，正反馈帮助PCA实现自加速降解。结果证明，PCA/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，PCA也被证明在传递治疗基因p53方面是有效的。更重要的是，PCA/p53复合物可以通过PCA和p53的协同作用显著诱导肿瘤细胞的生长抑制，为设计自扩增ros响应聚合基因载体提供了有价值的见解。

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Cinnamaldehyde-Based ROS-Responsive Polymeric Gene Vectors for Efficient Gene Delivery and Tumor Cell Growth Inhibition

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 (CA)-based ROS-responsive cationic polymer (PCA) and demonstrate its high efficiency in gene delivery and tumor cell growth inhibition. CA could be released from the polymer via a ROS-sensitive thioacetal bond by endogenous ROS. The released CA successively induced more ROS accumulation through GSH depletion, and the positive feedback helped PCA to achieve self-accelerating degradation. Results proved that PCA/p53 complexes were efficient in depleting GSH, upregulating ROS levels, and gene transfection. Besides, PCA was also shown to be effective in delivering the therapeutic gene p53. More importantly, PCA/p53 complexes could significantly induce tumor cell growth suppression by a synergistic effect of PCA and p53, providing valuable insights into the design of self-amplifying ROS-responsive polymeric gene vectors.

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.