School of Medicine, South China University of Technology, Guangzhou, 510006, PR China.
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, PR China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, 510006, PR China.
Biomaterials. 2022 Oct;289:121795. doi: 10.1016/j.biomaterials.2022.121795. Epub 2022 Sep 7.
Although stimuli-responsive polymers have emerged as promising strategies for intelligent cancer therapy, limited polymer degradation and insufficient drug release remain a challenge. Here, we report a novel reactive oxygen species (ROS)-awakened self-amplifying degradable cinnamaldehyde (CA)-based poly(thioacetal) polymer. The polymer consists of ROS responsive thioacetal (TA) group and CA as the ROS generation agent. The self-amplified polymer degradation process is triggered by endogenous ROS-induced cleavage of the TA group to release CA. The CA released then promotes the generation of more ROS through mitochondrial dysfunction, resulting in amplified polymer degradation. More importantly, poly(thioacetal) itself can trigger immunogenic cell death (ICD) of the tumor cells and its side chains can be conjugated with indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor to reverse the immunosuppressive tumor microenvironment for synergistic cancer immunotherapy. The self-amplified degradable poly(thioacetal) developed in this work provides insights into the development of novel stimulus-responsive polymers for enhanced cancer immunotherapy.
虽然刺激响应聚合物已成为智能癌症治疗的有前途的策略，但聚合物的有限降解和药物释放不足仍然是一个挑战。在这里，我们报告了一种新型的活性氧（ROS）唤醒的自扩增可降解肉桂醛（CA）基聚硫缩醛聚合物。该聚合物由 ROS 响应性硫缩醛（TA）基团和 CA 组成，作为 ROS 生成剂。自扩增聚合物的降解过程是由内源性 ROS 诱导的 TA 基团的断裂触发的，以释放 CA。释放的 CA 然后通过线粒体功能障碍促进更多 ROS 的产生，导致聚合物的放大降解。更重要的是，聚硫缩醛本身可以触发肿瘤细胞的免疫原性细胞死亡（ICD），其侧链可以与吲哚胺 2,3-双加氧酶 1（IDO-1）抑制剂结合，以逆转免疫抑制的肿瘤微环境，实现协同癌症免疫治疗。本工作中开发的自扩增可降解聚硫缩醛为增强癌症免疫治疗提供了一种新型刺激响应聚合物的发展思路。
