Zeng Lingwu, Li Yang, Li Tianyu, Cao Wei, Yi Yu, Geng Weijia, Sun Zhiwei, Xu Huaping
Key Lab of Organic Optoelectronics & Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084 (China).
Chem Asian J. 2014 Aug;9(8):2295-302. doi: 10.1002/asia.201402256. Epub 2014 May 20.
We report the preparation of selenium-containing platinum-based anticancer drug EG-Se/Pt. EG-Se/Pt was obtained from the coordination of selenium-containing molecules (EG-Se) with cisplatin (CDDP). The structure of EG-Se/Pt was characterized by (1) H and (77) Se NMR spectroscopy, XPS, ESI-MS, and MALDI-TOF. In aqueous solution, EG-Se/Pt self-assembles to form spherical aggregates. EG-Se/Pt shows enhanced stability against dilution and high salt concentration compared with EG-Se. EG-Se/Pt induces cell apoptosis via reactive oxygen species (ROS), which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays. More importantly, EG-Se/Pt effectively inhibits tumor growth in vivo in tumor-bearing mice. It is anticipated that tuning the ROS level through the assembly of selenium-containing molecules can be a general method to realize anticancer selectivity.
我们报道了含硒铂基抗癌药物EG-Se/Pt的制备。EG-Se/Pt是由含硒分子(EG-Se)与顺铂(CDDP)配位得到的。通过(1)H和(77)Se NMR光谱、XPS、ESI-MS和MALDI-TOF对EG-Se/Pt的结构进行了表征。在水溶液中,EG-Se/Pt自组装形成球形聚集体。与EG-Se相比,EG-Se/Pt在稀释和高盐浓度下表现出更高的稳定性。EG-Se/Pt通过活性氧(ROS)诱导细胞凋亡,这导致在细胞毒性试验中癌细胞和正常细胞之间具有高选择性。更重要的是,EG-Se/Pt在荷瘤小鼠体内能有效抑制肿瘤生长。预计通过含硒分子的组装来调节ROS水平可能是实现抗癌选择性的一种通用方法。