Dong Kai, Yang Chunrong, Yan Yan, Wang Pengchong, Sun Ying, Wang Ke, Lu Tingli, Chen Qiang, Zhang Yanni, Xing Jianfeng, Dong Yalin
Department of Pharmacy, The first Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
J Mater Chem B. 2018 Feb 21;6(7):1105-1117. doi: 10.1039/c7tb02973j. Epub 2018 Feb 6.
Reactive oxygen species (ROS) are one of the major intracellular metabolites. Tumor cells are usually under oxidative stress and susceptible to further ROS insults due to the excessive increase in ROS levels. Moreover, tumor cells also upregulate antioxidant systems such as glutathione (GSH) to counteract the damage caused by ROS. Therefore, the amplification of oxidative stress through increasing ROS levels to induce apoptosis could be a strategy for tumor therapy. Here we report a redox-responsive polymer micellar system, which is composed of Pluronic F127-disulfide bond-d-α-tocopheryl polyethylene glycol succinate (F127-SS-TPGS, FSST). The micelles could be degraded by the cleavage of the disulfide bond in the reductive intracellular environment, and release the ROS inducer, TPGS, which induced cytotoxicity through elevating ROS levels and inhibited mitochondrial function in tumor cells. These micelles hardly affected the function of normal cells and showed good biocompatibility. The paclitaxel-loaded FSST-PTX micelles significantly improved the cytotoxicity of PTX. In vivo experiments revealed that the FSST-PTX micelles prolonged the circulation and enhanced the treatment of PTX. In conclusion, FSST could be a potential vehicle for cancer treatment.
活性氧（ROS）是主要的细胞内代谢产物之一。肿瘤细胞通常处于氧化应激状态，由于ROS水平过度升高，它们易受到进一步的ROS损伤。此外，肿瘤细胞还会上调抗氧化系统，如谷胱甘肽（GSH），以对抗ROS造成的损伤。因此，通过增加ROS水平来放大氧化应激以诱导细胞凋亡可能是一种肿瘤治疗策略。在此，我们报道了一种氧化还原响应性聚合物胶束系统，它由普朗尼克F127-二硫键-d-α-生育酚聚乙二醇琥珀酸酯（F127-SS-TPGS，FSST）组成。胶束可在还原性细胞内环境中通过二硫键的断裂而降解，并释放ROS诱导剂TPGS，TPGS通过提高ROS水平诱导细胞毒性并抑制肿瘤细胞的线粒体功能。这些胶束几乎不影响正常细胞的功能，并表现出良好的生物相容性。负载紫杉醇的FSST-PTX胶束显著提高了PTX的细胞毒性。体内实验表明，FSST-PTX胶束延长了循环时间并增强了PTX的治疗效果。总之，FSST可能是一种潜在的癌症治疗载体。
