Lysosome-Targeting Iridium(III) Probe with Near-Infrared Emission for the Visualization of NO/O-2(center dot-) Crosstalk via In Vivo Peroxynitrite Imaging

摘要

Nitric oxide (NO) and superoxide anions (O-2(center dot-)) are two noteworthy reactive species implicated in various physiological and pathological processes, such as ROS-induced lysosomal cell death. The interaction ("crosstalk") between them may form a new mediator peroxynitrite (ONOO) which has implications for cancer, diabetes, Alzheimer's disease, and liver-damage. It is therefore essential to investigate lysosomal NO/O-2(center dot-) cross-talk in vivo through ONOO- responsive molecular tools in order to fully comprehend the physiological and pathological mechanisms involved. In this study, a lysosome-targeting iridium(III) complex, Ir-NIR, has been investigated as a near-infrared (MR) phosphorescent probe for visualizing NO/O-2(center dot-) cross-talk by the phosphorescent detection of endogenous ONOO levels in vivo. Ir-NIR exhibits a rapid (within 200 s), highly sensitive, and approximately 100-fold enhanced response to ONOO- in phosphorescence intensity. Thus, these characteristics, coupled with good cell permeability and low cytotoxicity, enable the probe to be used to detect intracellular ONOO- living organisms both in vitro and in vivo.