Department of Biomedical Engineering, National Yang Ming University, Taipei 112, Taiwan, ROC.
Department of Biomedical Engineering, National Yang Ming University, Taipei 112, Taiwan, ROC; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang Ming University, Taipei 112, Taiwan, ROC; Biomedical Engineering Research Center, National Yang Ming University, Taipei 112, Taiwan, ROC.
Biomaterials. 2015 Aug;61:150-61. doi: 10.1016/j.biomaterials.2015.05.007. Epub 2015 May 15.
This study developed reactive oxygen species (ROS) and glutathione (GSH) dual redox-responsive micelles, which encapsulate anticancer drug camptothecin (CPT), protect CPT activity, and trigger CPT release in cancer cell H2O2- or GSH-rich surroundings. Experimental results show that CPT-loaded dual redox-responsive micelles remain stable at low levels of ROS and GSH in blood circulation, have high redox sensitivities needed to CPT release in cancer cells with high ROS or GSH (e.g., lung, gastric, and colon cancer cells), and prevent undersigned CPT toxicity in ROS/GSH balanced normal cells (e.g., fibroblast cells, etc.) or normal organs (e.g., liver, kidney, etc.). The CPT-loaded dual redox-responsive micelles also had high in vivo antitumor efficacy. This study demonstrates that ROS and GSH dual redox-responsive micelles have potential use as anticancer therapeutic nanomedicine in various cancer therapies.
本研究开发了活性氧（ROS）和谷胱甘肽（GSH）双重氧化还原响应性胶束，可包载抗癌药物喜树碱（CPT），保护 CPT 活性，并在富含 H2O2 或 GSH 的肿瘤细胞环境中触发 CPT 释放。实验结果表明，CPT 负载的双重氧化还原响应性胶束在血液中 ROS 和 GSH 水平较低时保持稳定，在 ROS 或 GSH 水平较高的肿瘤细胞（如肺癌、胃癌和结肠癌细胞）中具有释放 CPT 所需的高氧化还原敏感性，并防止 CPT 在 ROS/GSH 平衡的正常细胞（如成纤维细胞等）或正常器官（如肝脏、肾脏等）中产生毒性。载 CPT 的双重氧化还原响应性胶束也具有很高的体内抗肿瘤疗效。本研究表明，ROS 和 GSH 双重氧化还原响应性胶束有望作为各种癌症治疗中的抗癌治疗性纳米医学。
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