Son Aoi, Kawasaki Atsushi, Hara Daiki, Ito Takeo, Tanabe Kazuhito
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504.
Chemistry. 2015 Feb 2;21(6):2527-36. doi: 10.1002/chem.201404979. Epub 2014 Dec 9.
Understanding oxygen fluctuation in a cancerous tumor is important for effective treatment, especially during radiotherapy. In this paper, ruthenium complexes bearing a nitroimidazole group are shown to report the oxygen status in tumor tissue directly. The nitroimidazole group was known to be accumulated in hypoxic tumor tissues. On the other hand, the ruthenium complex showed strong phosphorescence around 600 nm. The emission of ruthenium is quenched instantaneously by molecular oxygen due to energy transfer between triplet states of oxygen and ruthenium complex, but the emission is then recovered by the removal of oxygen. Thus, we could observe oxygen fluctuation in tumor tissue in a real-time manner by monitoring the phosphorescence of the ruthenium complex. The versatility of the probe is demonstrated by monitoring oxygen fluctuation in living cells and tumor tissue planted in mice. The ruthenium complex promptly penetrated plasma membrane and accumulated in cells to emit its oxygen-dependent phosphorescence. In vivo experiments revealed that the oxygen level in tumor tissue seems to fluctuate at the sub-minute timescale.
了解癌性肿瘤中的氧波动对于有效治疗至关重要，尤其是在放射治疗期间。在本文中，带有硝基咪唑基团的钌配合物被证明可以直接报告肿瘤组织中的氧状态。已知硝基咪唑基团会在缺氧的肿瘤组织中积累。另一方面，钌配合物在600 nm左右显示出强烈的磷光。由于氧和钌配合物的三重态之间的能量转移，钌的发射会被分子氧瞬间淬灭，但随后通过去除氧发射又会恢复。因此，通过监测钌配合物的磷光，我们可以实时观察肿瘤组织中的氧波动。通过监测活细胞和植入小鼠体内的肿瘤组织中的氧波动，证明了该探针的多功能性。钌配合物能迅速穿透质膜并在细胞中积累，发出其依赖氧的磷光。体内实验表明，肿瘤组织中的氧水平似乎在亚分钟时间尺度上波动。
