School of Material Science and Chemical Engineering , Ningbo University , Ningbo 315211 , China.
School of Chemical Engineering , Sichuan University , Chengdu 610065 , China.
Biomacromolecules. 2018 Dec 10;19(12):4658-4667. doi: 10.1021/acs.biomac.8b01423. Epub 2018 Nov 16.
Due to the high oxidative stress of the tumor microenvironment, more and more researchers have been devoted to reactive oxygen species (ROS)-responsive nanodrug delivery systems for anticancer therapy. Herein, a ROS-responsive moiety, thioacetal, was synthesized, and cinnamaldehyde (CA) was introduced in the polymer chain to trigger the generation of ROS to expect the enhancement of the ROS-responsive effect. The poly(ester-thioacetal) mPEG2k - b-(NTA-HD) polymer, its self-assembled micelles, and the ROS-responsive behavior were characterized by H NMR and DLS. The anticancer drug doxorubicin (DOX) was adopted to prepare DOX-loaded poly(ester-thioacetal) micelles. The intracellular ROS detection indicated that the mPEG2k - b-(NTA-HD) polymer could degrade via the high concentration of ROS in cancer cells, and the released CA stimulated mitochondria to regenerate additional ROS. The flow cytometry results indicated that the ROS-responsive polymeric micelles showed faster cellular uptake compared to the control mPEG2k - b-PCL5k micelles. The ROS responsive DOX/mPEG2k - b-(NTA-HD) micelles exhibited much better anticancer efficiency on both 4T1 and HeLa cancer cells than DOX/mPEG2k - b-PCL5k micelles.
由于肿瘤微环境的氧化应激较高，越来越多的研究人员致力于开发针对活性氧（ROS）的纳米药物递送系统以进行抗癌治疗。在此，合成了一种 ROS 响应性部分，硫缩醛，并在聚合物链中引入肉桂醛（CA）以引发 ROS 的产生，期望增强 ROS 响应性。通过 1H NMR 和 DLS 对聚（酯-硫缩醛）mPEG2k-b-（NTA-HD）聚合物、其自组装胶束及其 ROS 响应行为进行了表征。采用阿霉素（DOX）制备了 DOX 负载的聚（酯-硫缩醛）胶束。细胞内 ROS 检测表明，mPEG2k-b-（NTA-HD）聚合物可以通过癌细胞中高浓度的 ROS 进行降解，释放的 CA 刺激线粒体产生额外的 ROS。流式细胞术结果表明，与对照 mPEG2k-b-PCL5k 胶束相比，ROS 响应性聚合物胶束具有更快的细胞摄取速度。ROS 响应性 DOX/mPEG2k-b-（NTA-HD）胶束对 4T1 和 HeLa 癌细胞的抗癌效率均明显优于 DOX/mPEG2k-b-PCL5k 胶束。
