Modulation of Glutathione Levels by Redox-Active Nanogel Carriers for the Synergistic Enhancement of Photodynamic Therapy
Modulation of Glutathione Levels by Redox-Active Nanogel Carriers for the Synergistic Enhancement of Photodynamic Therapy
复制标题
氧化还原活性纳米凝胶载体调节谷胱甘肽水平以协同增强光动力疗法
DOI：
10.1002/adtp.201800113
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Wang Chang-Chun
中科院分区：
文献类型：
--
作者：
Zhang Zi-Hao;Ding Yu-Xue;Li Yong-Jing;Wu Pan;Guo Jia;Wang Chang-Chun
由于肿瘤细胞的氧化还原调节机制，光动力疗法（PDT）中常用的光敏剂的治疗效果在临床试验中仍远不能令人满意，氧化还原调节机制在其抗肿瘤活性之前消除了所产生的活性氧（ROS）。在此，提出了一种新的途径，大大提高PDT的效率，通过细胞内反应，发生在复合纳米凝胶与Fe 3 O 4纳米簇在其核心和二硫键交联的磷酰胆碱在其外壳。这些氧化还原活性纳米凝胶能够通过硫醇-二硫键交换反应下调内源性谷胱甘肽（GSH）水平，这导致由包封的光敏剂（氯6）产生的细胞毒性ROS的优先积累，用于细胞凋亡和肿瘤生长抑制。除了二硫化物辅助的PDT之外，复合纳米凝胶还表现出改善的细胞摄取、循环时间、靶向分布、细胞内降解和选择性毒性，这为使用这些纳米凝胶作为简单、安全和有效的癌症治疗提供了很大的希望。
The therapeutic efficiency of commonly used photosensitizers in photodynamic therapy (PDT) remains far from satisfactory in clinical trials due to the redox regulation mechanisms of cancer cells, which eliminates the generated reactive oxygen species (ROS) prior to their antitumor activity. Herein, a novel pathway to greatly enhance the efficiency of PDT is proposed through an intracellular reaction that occurs in composite nanogels with Fe3O4nanoclusters in their core and disulfide‐crosslinked phosphorylcholines in their shell. These redox‐active nanogels are able to downregulate the endogenous glutathione (GSH) levels via a thiol‐disulfide exchange reaction, which results in the preferential accumulation of cytotoxic ROS generated by the encapsulated photosensitizer (Chlorine 6) for cell apoptosis and tumor‐growth inhibition. In addition to disulfide‐assisted PDT, the composite nanogel exhibits improved cellular uptake, circulation time, targeted distribution, intracellular degradation, and selective toxicity, which provides great promise for the use of these nanogels as a simple, safe, and effective cancer treatment.