Phosphorescent Ir(III) complexes conjugated with oligoarginine peptides serve as optical probes for in vivo microvascular imaging

Abstract

Imaging the vascular structures of organ and tumor tissues is extremely important for assessing various pathological conditions. Herein we present the new vascular imaging probe BTQ-Rn (n = 8, 12, 16), a phosphorescent Ir(III) complex containing an oligoarginine peptide as a ligand. This microvasculature staining probe can be chemically synthesized, unlike the commonly used tomato lectins labeled with a fluorophore such as fluorescein isothiocyanate (FITC). Intravenous administration of BTQ-R12 to mice and subsequent confocal luminescence microscope measurements enabled in vivo vascular imaging of tumors and various organs, including kidney, liver and pancreas. Dual color imaging of hepatic tissues of living mice fed a high-fat diet using BTQ-R12 and the lipid droplet-specific probe PC6S revealed small and large lipid droplets in the hepatocytes, causing distortion of the sinusoidal structure. BTQ-R12 selectively stains vascular endothelium and thus allows longer-term vascular network imaging compared to fluorescent dextran with a molecular weight of 70 kDa that circulate in the bloodstream. Furthermore, time-gated measurements using this phosphorescent vascular probe enabled imaging of blood vessel structures without interference from autofluorescence.

Red Light-Emitting Water-Soluble Luminescent Iridium-Containing Polynorbornenes: Synthesis, Characterization and Oxygen Sensing Properties in Biological Tissues In Vivo

“…Iridium(III) complexes are the most promising probes for the evaluation of oxygen status in biological objects because of their photostability, readily tunable emission color, high quantum yields and relatively short emission lifetimes. A number of oxygen probes based on luminescent iridium(III) complexes have been developed [22,[27][28][29][30][31]. Amphiphilic polymers with chemically bonded phosphorescent iridium(III) complexes are attractive oxygen probes because the hydrophilic units of these polymers prevent the interaction of hydrophobic phosphorescent units with different biomolecules of the biological object and minimize the distortion of oxygen content evaluation.…”

“…In the last decade, a number of iridium luminophores have been synthesized and their use as phosphorescent oxygen sensors in tumor cells and tissues has been demonstrated [22,[27][28][29]. Neutral and ionic deep red emitting iridium(III) complexes have been obtained recently and their applicability as oxygen-sensing probes in live cells and tissues was investigated in detail [30,31]. Meanwhile, the search for new sensors that are more suitable for biological applications is still in demand to meet the requirements of high water solubility, low toxicity, high phosphorescence quantum yield and strong dependence of phosphorescence signal on oxygen concentration in the physiological range.…”

Molecularly Engineered Room-Temperature Phosphorescence for Biomedical Application: From the Visible toward Second Near-Infrared Window

“…For example, to achieve in vivo microvascular bioimaging, phosphorescent Ir(III) complexes conjugated by various arginine peptides were fabricated. 284 The emission decay profiles behaved in a decay manner like a single-exponential function. The phosphorescence quantum yield and lifetime taken in deaerated solutions were up to 30% and 5.9 μs, respectively.…”

Progress of Nanomaterials in Photodynamic Therapy Against Tumor

“…Ir NPs might be promising alternatives to traditional organic PSs. Ir (III) complexes show great potential in the construction of oxygen-sensitive sensing probes due to their unique oxygen quenching pathway ( Yasukagawa et al, 2021 ). Xiao et al designed and synthesized a red light-excited Ir (III) complex encapsulated in the hydrophobic pocket of Cyanine7-modified β-cyclodextrin (β-CD) Xiao and Yu (2021) .…”