Yoshihara Kazuki, Takagi Kohei, Son Aoi, Kurihara Ryohsuke, Tanabe Kazuhito
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto, 615-8510, Japan.
Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, 5-10-1 Fuchinobe, Chuo-ku, Sagamihara, 252-5258, Japan.
Chembiochem. 2017 Aug 17;18(16):1650-1658. doi: 10.1002/cbic.201700116. Epub 2017 Jun 28.
The use of DNA aggregates could be a promising strategy for the molecular imaging of biological functions. Herein, phosphorescent oligodeoxynucleotides were designed with the aim of visualizing oxygen fluctuation in tumor cells. DNA-ruthenium conjugates (DRCs) that consisted of oligodeoxynucleotides, a phosphorescent ruthenium complex, a pyrene unit for high oxygen responsiveness, and a nitroimidazole unit as a tumor-targeting unit were prepared. In general, oligonucleotides have low cell permeability because of their own negative charges; however, the DRC formed aggregates in aqueous solution due to the hydrophobic pyrene and nitroimidazole groups, and smoothly penetrated the cellular membrane to accumulate in tumor cells in a hypoxia-selective manner. The oxygen-dependent phosphorescence of DRC in cells was also observed. In vivo experiments revealed that aggregates of DRC accumulated in hypoxic tumor tissue that was transplanted into the left leg of mice, and showed that oxygen fluctuations in tumor tissue could be monitored by tracking of the phosphorescence emission of DRC.
使用DNA聚集体可能是一种用于生物功能分子成像的有前景的策略。在此，设计了磷光寡脱氧核苷酸，目的是可视化肿瘤细胞中的氧波动。制备了由寡脱氧核苷酸、磷光钌配合物、用于高氧响应性的芘单元和作为肿瘤靶向单元的硝基咪唑单元组成的DNA-钌缀合物（DRC）。一般来说，寡核苷酸由于自身带负电荷而具有低细胞渗透性；然而，由于疏水的芘和硝基咪唑基团，DRC在水溶液中形成聚集体，并以缺氧选择性方式顺利穿透细胞膜并在肿瘤细胞中积累。还观察到细胞中DRC的氧依赖性磷光。体内实验表明，DRC聚集体在移植到小鼠左腿的缺氧肿瘤组织中积累，并表明通过跟踪DRC的磷光发射可以监测肿瘤组织中的氧波动。
