当前位置：
X-MOL 学术
›
Mol. Pharmaceutics
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Amplification of Oxidative Stress in MCF-7 Cells by a Novel pH-Responsive Amphiphilic Micellar System Enhances Anticancer Therapy
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-01-02 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00973 Kai Dong 1 , Qiuya Lei 1 , Hongfei Qi 1 , Yanni Zhang 1 , Ning Cui 1 , Xianglong Wu 1 , Li Xie 1 , Xiaocheng Yan 2 , Tingli Lu 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-01-02 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00973 Kai Dong 1 , Qiuya Lei 1 , Hongfei Qi 1 , Yanni Zhang 1 , Ning Cui 1 , Xianglong Wu 1 , Li Xie 1 , Xiaocheng Yan 2 , Tingli Lu 1
Affiliation
|
The excessive increase of intracellular reactive oxygen species (ROS) makes tumor cells usually in the state of oxidative stress. Although tumor cells can adapt to this state to a certain extent by upregulating antioxidant systems, the further ROS insults disrupt the transient intracellular redox balance, eventually leading to apoptosis and necrosis. Therefore, increasing the intracellular ROS level can effectively amplify the oxidative stress and induce apoptosis, which can be employed as a strategy for tumor treatment. Herein, a unique pH-responsive ROS inducing micellar system was reported in this study to specifically amplify the ROS signal in tumor cells. This micellar system was constructed by a new amphiphilic polymer, PIAThydCA, composed of poly(itaconic acid) (PIA) as the hydrophilic backbone, d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as the hydrophobic side chain, and cinnamaldehyde (CA) as the ROS-generating agent, which were linked to PIA by the pH-sensitive hydrazone bond. PIAThydCA micelles could be degraded in the intracellular acidic environment through the hydrolysis of hydrazone bond and release CA. CA and TPGS could amplify oxidative stress cooperatively to kill MCF-7 human breast cells preferentially through the mitochondrial apoptosis pathway. Therefore, we anticipate that the PIAThydCA micelles could exert great potential in anticancer therapy.
中文翻译：
通过新型pH响应两亲胶束系统放大MCF-7细胞中的氧化应激可增强抗癌治疗能力。
细胞内活性氧（ROS）的过度增加使肿瘤细胞通常处于氧化应激状态。尽管肿瘤细胞可以通过上调抗氧化系统在一定程度上适应这种状态，但进一步的ROS损伤破坏了瞬时的细胞内氧化还原平衡，最终导致细胞凋亡和坏死。因此，增加细胞内ROS水平可以有效地放大氧化应激并诱导细胞凋亡，这可以用作肿瘤治疗的策略。本文中，本研究报道了独特的pH响应ROS诱导胶束系统，可特异性扩增肿瘤细胞中的ROS信号。该胶束系统由新型两亲聚合物PIAT hyd CA构建而成，该聚合物由聚衣康酸（PIA）作为亲水性骨架，d -α-生育酚聚乙二醇1000琥珀酸酯（TPGS）作为疏水侧链，而肉桂醛（CA）作为ROS生成剂，它们通过pH敏感的键与PIA连接。PIAT hyd CA胶束可在的酸性环境中通过键的水解而降解并释放出CA。CA和TPGS可以协同增强氧化应激，通过线粒体凋亡途径优先杀死MCF-7人乳腺细胞。因此，我们预计PIAT hyd CA胶束可以在抗癌治疗中发挥巨大潜力。
更新日期：2019-01-02
中文翻译：
通过新型pH响应两亲胶束系统放大MCF-7细胞中的氧化应激可增强抗癌治疗能力。
细胞内活性氧（ROS）的过度增加使肿瘤细胞通常处于氧化应激状态。尽管肿瘤细胞可以通过上调抗氧化系统在一定程度上适应这种状态，但进一步的ROS损伤破坏了瞬时的细胞内氧化还原平衡，最终导致细胞凋亡和坏死。因此，增加细胞内ROS水平可以有效地放大氧化应激并诱导细胞凋亡，这可以用作肿瘤治疗的策略。本文中，本研究报道了独特的pH响应ROS诱导胶束系统，可特异性扩增肿瘤细胞中的ROS信号。该胶束系统由新型两亲聚合物PIAT hyd CA构建而成，该聚合物由聚衣康酸（PIA）作为亲水性骨架，d -α-生育酚聚乙二醇1000琥珀酸酯（TPGS）作为疏水侧链，而肉桂醛（CA）作为ROS生成剂，它们通过pH敏感的键与PIA连接。PIAT hyd CA胶束可在的酸性环境中通过键的水解而降解并释放出CA。CA和TPGS可以协同增强氧化应激，通过线粒体凋亡途径优先杀死MCF-7人乳腺细胞。因此，我们预计PIAT hyd CA胶束可以在抗癌治疗中发挥巨大潜力。
京公网安备 11010802027423号