Lysosome-Targeting Iridium(III) Probe with Near-Infrared Emission for the Visualization of NO/O2•- Crosstalk via In Vivo Peroxynitrite Imaging

Nitric oxide (NO) and superoxide anions (O2•-) 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/O2•- crosstalk 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 (NIR) phosphorescent probe for visualizing NO/O2•- crosstalk 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.