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

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 monolayer cultures and 3D multicellular tumor spheroids (MCTSs). The cytotoxicity of Ru-ipad was in accordance with its suppression of the hypoxia-inducible factor-1α (HIF-1α) 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-1α expression. The discovery of this dual-function ruthenium(II) anthraquinone complex may represent an important advance in hypoxic solid tumor treatment.