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

Abstract

Nitric oxide (NO) and superoxide anions (O 2 •-) 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•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/O 2•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.N itric oxide (NO) and superoxide anions (O 2 •-) are two noteworthy reactive species implicated in various physiological and pathological processes. 1,2 Recently, increased research in the area has revealed that cellular NO and O 2•-

Endogenous Stimuli-Responsive DNA Nanostructures Toward Cancer Theranostics

“…Secondly, attention on the endogenous stimuli mentioned is primarily restricted to pH, small molecules, enzymes and nucleic acids. Other molecules indicative of tumor pathological features, including peroxynitrite (Wu et al, 2020), H 2 S (An et al, 2018), and hormones (Sun and Zhao, 2017), present a larger library of stimuli for creating stimuli-responsive DNA nanostructures, conducive to broadening the applications in bioimaging and biomedicine. Thirdly, due to the complexity of the cancer treatment mechanisms, DNA nanostructures responding to multi-stimuli and including multiple therapeutic components such as proteins, genes, antibodies, photothermal agents and photosensitizers represent the general trend in clinical treatment, aiming at improving the medical precision and augmenting the curative effects.…”

Near-infrared emitting iridium complexes: Molecular design, photophysical properties, and related applications

“…Before and after the reactions, the emission properties of the probes changed by a wide margin, in terms of emission wavelength, emission intensity or emission lifetime. With the help of these changes, not limited to bio-imaging, qualitative or even semi-quantitative analyses have been realized to detect certain species of particles or structural units, such as proton (H + ) ( Zheng et al., 2017 ), cysteine (Cys) and homocysteine (Hcy) ( Li et al., 2020 ; Wu et al., 2017 ), peroxynitrite (ONOO − ) ( Li et al., 2019 ; Wu et al., 2020 ), l-azidohomoalanine ( Wang et al., 2017a ), human carboxylesterase 2 (hCE2) ( Yan et al., 2018 ), and phase-separated biomolecular condensates ( Yan et al., 2021 ).…”

“…Later in 2020, Chao et al. reported another cationic Ir(III) complex Ir-NIR for specific ONOO − detection, which uses diphenylquinoxaline derivatives as cyclometalated ligands as shown in Figure 23 A ( Wu et al., 2020 ). The secondary amine substituted on the ancillary ligand is quencher for phosphorescent emission.…”

“… (D) Phosphorescence intensity at 702 nm of Ir-NIR (5 μM) toward 10 equiv various species (blank, 1 O 2 , H 2 O 2 , O 2 · - , ClO − , NO 2 − , NO 3 − , ·OH, NO, AA (ascorbic acid), DHA (dehydroascorbate), L-Cys (L-cysteine), GSH (glutathione), and ONOO − ) for 600 s in PBS solution (λ ex = 405 nm; slits:5/5 nm). ( Wu et al., 2020 ). Copyright 2020 American Chemical Society.…”

Robust Packing of a Self‐Assembling Iridium Complex via Endocytic Trafficking for Long‐Term Lysosome Tracking

“…Meanwhile, iridium(III) complexes were developed for lysosome imaging due to their advantageous photophysical properties and sub-organelle selectivity. [6] By far, the best record was achieved by a water-soluble morpholine attached triscyclometalated iridium(III) complex that labeled lysosomes till passage 4 cells with a high labeling rate. However, the phosphorescence intensity declined a lot after each cell passaging.…”