Smart Bimodal Imaging of Hypochlorous Acid In Vivo Using a Heterobimetallic Ruthenium(II)-Gadolinium(III) Complex Probe.

Abstract

A unique heterobimetallic Ru(II)-Gd(III) complex, Ru-AN-Gd, is reported to serve as an effective probe for bimodal phosphorescence-magnetic resonance (MR) imaging of hypochlorous acid (HClO) in vitro and in vivo. The probe was designed by incorporating a MR contrast agent, Gd-DOTA, into a HClO-responsive bipyridine-Ru(II) complex derivative. The specific reaction between Ru-AN-Gd and HClO triggers the cleavage of an ether bond in the probe molecule, resulting in phosphorescence turn-on and MR turn-off responses to HClO. The integration of MR and phosphorescence detection modes allows the probe to be employed for detecting HClO in a quite wide concentration range (0.6-2000 μM) and for imaging HClO at various resolutions ranging from the subcellular level to the whole body without a depth limit. Its applicability was demonstrated by phosphorescence imaging of lysosomal HClO in live cells, visualization of HClO generation in a mouse arthritis model, and bimodal phosphorescence-MR imaging of HClO in drug-induced acute liver and kidney injury of a mouse. The research achievements suggested the potential of Ru-AN-Gd for diagnosis and treatment monitoring of HClO-related disease.