PH-Sensitive Near-IR Emitting Dinuclear Ruthenium Complex for Recognition, Two-Photon Luminescent Imaging, and Subcellular Localization of Cancer Cells.

Abstract

A dinuclear Ru(II) complex of [(bpy)2Ru(Hdip)Ru(H2bip)](ClO4)4 {bpy is 2,2'-bipyridine, Hdip is 2-(2,6-di(pyridin-2-yl)-pyridin-4-yl)-1H-imidazo[4,5-f]-[1,10]phenanthroline, and H2bip is 2,6-bis(imidazole-2-yl)-pyridine} was synthesized and characterized by elemental analysis, mass spectrometry, and 1H NMR spectroscopy. Spectrophotometric pH titrations in aqueous buffer and in vitro cell experiments indicated the response ability of the complex to pH fluctuations in the physiological pH range (6.0-8.0). The complex was found to be capable of differentiating live HeLa cells from healthy HEK293 cells by selectively accumulating in lysosomes of the HeLa cells. The low cytotoxicity (IC50 > 100 μM), a large Stokes shift (∼200 nm), strong near-IR emission at ∼700 nm, a relatively long excited state lifetime, high photostability, and solubility make this complex considerably promising in real-time tracking and visualization of lysosomes in live cells. More interestingly, the tumor cell-specific two-photon luminescent imaging properties also endow this Ru complex with potential for applications in high-resolution tumor imaging and luminescence-guided tumor resection.