A ruthenium(II) anthraquinone complex as the theranostic agent combining hypoxia imaging and HIF-1 alpha inhibition

作者：Wang, Jinquan^*; Kou, Junfeng; Hou, Xiaojuan; Zhao, Zizhuo; Chao, Hui^*

来源：Inorganica Chimica Acta, 2017, 454: 176-183.

DOI：10.1016/j.ica.2016.04.050

• Ruthenium(II) complex
• Hypoxia
• Probe
• HIF-1 alpha
• Antitumor

Hypoxia is a common feature of most solid tumors and its precise imaging is of great importance to therapy planning. Here we demonstrated that a ruthenium(II) anthraquinone complex [Ru(bpy)(2)(ipad)] (ClO4)(2) (Ru-ipad, where bpy = 2,2'-bipyridine and ipad = 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f] [1,10]phenanthroline), is a powerful optical probe that can detect repeated cycles of hypoxia-normoxia in living cells in real time. This hypoxia probe also showed cytotoxicity against hypoxic 2D cancer mono layer cultures and 3D multicellular tumor spheroids (MCTSs). The cytotoxicity of Ru-ipad was in accordance with its suppression of the hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein in tumor cells. Therefore, Ru-ipad not only has the potential to detect hypoxia with high sensitivity but also displays hypoxia-targeted antitumor effects through the inhibition of HIF-1 alpha expression. The discovery of this dual-function ruthenium(II) anthraquinone complex may represent an important advance in hypoxic solid tumor treatment.

• 出版日期2017-1-1
• 单位云南师范大学; 湖南医药学院; 广东药科大学; 中山大学