Ratiometric oxygen probes with a cell-penetrating peptide for imaging oxygen levels in living cells

Yasukagawa, Mami; Yamada, Keiichi; Tobita, Seiji; Yoshihara, Toshitada

doi:10.1016/j.jphotochem.2019.111983

Cited by 13 publications

(7 citation statements)

References 52 publications

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“…Typical applications include organic light-emitting diodes (OLED), light-emitting electrochemical cells, photoredox catalysts, photodynamic therapy (PDT), and bioimaging. − As an application for bioimaging, Ir(III) complexes have been used as optical probes for molecular oxygen (O 2 ) in living cells and tissues − in addition to other transition-metal complexes such as Pt(II) and Pd(II) porphyrins, − Ru(II) complexes, − and Pt(II) complexes . Oxygen levels are generally quantified based on lifetime measurements of phosphorescent probes, while ratiometric probes that do not require lifetime measurement have also been developed using phosphorescent metal complexes. − Although the lifetime-based method requires sophisticated equipment, the quantitative accuracy of in vivo measurements is generally superior to the ratiometric method.…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Emitting Ir(III) Complexes Bearing a Dipyrromethene Ligand for Oxygen Imaging of Deeper Tissues In Vivo

et al. 2022

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Phosphorescence lifetime imaging microscopy (PLIM) using a phosphorescent oxygen probe is an innovative technique for elucidating the behavior of oxygen in living tissues. In this study, we designed and synthesized an Ir(III) complex, PPYDM-BBMD, that exhibits long-lived phosphorescence in the near-infrared region and enables in vivo oxygen imaging in deeper tissues. PPYDM-BBMD has a π-extended ligand based on a mesomesityl dipyrromethene structure and phenylpyridine ligands with cationic dimethylamino groups to promote intracellular uptake. This complex gave a phosphorescence spectrum with a maximum at 773 nm in the wavelength range of the so-called biological window and exhibited an exceptionally long lifetime (18.5 μs in degassed acetonitrile), allowing for excellent oxygen sensitivity even in the near-infrared window. PPYDM-BBMD showed a high intracellular uptake in cultured cells and mainly accumulated in the endoplasmic reticulum. We evaluated the oxygen sensitivity of PPYDM-BBMD phosphorescence in alpha mouse liver 12 (AML12) cells based on the Stern−Volmer analysis, which gave an O 2 -induced quenching rate constant of 1.42 × 10 3 mmHg −1 s −1 . PPYDM-BBMD was administered in the tail veins of anesthetized mice, and confocal one-photon PLIM images of hepatic tissues were measured at different depths from the liver surfaces. The PLIM images visualized the oxygen gradients in hepatic lobules up to a depth of about 100 μm from the liver surfaces with a cellular-level resolution, allowing for the quantification of oxygen partial pressure based on calibration results using AML12 cells.

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Section: Introductionmentioning

confidence: 99%

Near-Infrared Emitting Ir(III) Complexes Bearing a Dipyrromethene Ligand for Oxygen Imaging of Deeper Tissues In Vivo

et al. 2022

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“…The most common compounds used as luminescent O 2 probes include Pt(II) and Pd(II) porphyrins, Ru(II) complexes, Pt(II) complexes, and Ir(III) complexes, which give intense phosphorescence in the visible to near-infrared wavelength regions with reasonably long lifetimes (> 1.0 μs). Oxygen probes targeting various biological tissues of interest have been developed by modifying these O 2 -sensing luminophores: cell-penetrating conjugates of Pt(II)-porphyrins 20 , 21 , dendritic Pt(II)- and Pd(II)-porphyrins 22 – 24 , Ru(II) complex derivatives targeting the cell nucleus 25 , ratiometric O 2 probes based on Ir(III) complexes 26 , 27 , etc.…”

Section: Introductionmentioning

confidence: 99%

In vivo O2 imaging in hepatic tissues by phosphorescence lifetime imaging microscopy using Ir(III) complexes as intracellular probes

Katano

Shiozaki

Yoshihara

et al. 2020

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Phosphorescence lifetime imaging microscopy (PLIM) combined with an oxygen (O2)-sensitive luminescent probe allows for high-resolution O2 imaging of living tissues. Herein, we present phosphorescent Ir(III) complexes, (btp)2Ir(acac-DM) (Ir-1) and (btp-OH)3Ir (Ir-2), as useful O2 probes for PLIM measurement. These small-molecule probes were efficiently taken up into cultured cells and accumulated in specific organelles. Their excellent cell-permeable properties allowed for efficient staining of three-dimensional cell spheroids, and thereby phosphorescence lifetime measurements enabled the evaluation of the O2 level and distribution in spheroids, including the detection of alterations in O2 levels by metabolic stimulation with an effector. We took PLIM images of hepatic tissues of living mice by intravenously administrating these probes. The PLIM images clearly visualized the O2 gradient in hepatic lobules with cellular-level resolution, and the O2 levels were derived based on calibration using cultured cells; the phosphorescence lifetime of Ir-1 gave reasonable O2 levels, whereas Ir-2 exhibited much lower O2 levels. Intravenous administration of NH4Cl to mice caused the hepatic tissues to experience hypoxia, presumably due to O2 consumption to produce ATP required for ammonia detoxification, suggesting that the metabolism of the probe molecule might affect liver O2 levels.

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“…Previous reports of excitation‐based Ir III ratiometric O 2 sensors describe the attachment of the phosphorescent metal complexes to a piperazine‐appended fluorophore [32a,d] . In 2020, a similar linker was used by our lab for the preparation of the chemiluminescent ratiometric pH sensor Ratio‐pHCL‐1 , coupling a pH sensitive carbofluorescein with a 1,2‐dioxetane [12] .…”

Section: Resultsmentioning

confidence: 99%

Chemiluminescent 1,2‐Dioxetane Iridium Complexes for Near‐Infrared Oxygen Sensing

et al. 2022

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Chemiluminescent iridium‐based sensors which demonstrate oxygen dependent responses have been developed. The molecular probes, named IrCL‐1, IrCL‐2 and IrCL‐3 consist of oxygen‐sensitive iridium complexes attached to a spiroadamantane 1,2 dioxetane and operate via energy transfer from the chemiexcited benzoate to the corresponding iridium(III) complex. Complexing the iridium(III) center with π‐extended ligands results in emission in the biologically relevant, near‐infrared (NIR) region. All probes demonstrate varying oxygen tolerance, with IrCL‐1 being the most oxygen sensitive. These probes have been further utilized for in vitro ratiometric imaging of oxygen, as well as for intraperitoneal, intramuscular and intratumoral imaging in live mice. To our knowledge, these are the first iridium‐based chemiluminescent probes that have been employed for in vitro ratiometric oxygen sensing, and for in vivo tumor imaging.

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Ratiometric oxygen probes with a cell-penetrating peptide for imaging oxygen levels in living cells

Cited by 13 publications

References 52 publications

Near-Infrared Emitting Ir(III) Complexes Bearing a Dipyrromethene Ligand for Oxygen Imaging of Deeper Tissues In Vivo

Near-Infrared Emitting Ir(III) Complexes Bearing a Dipyrromethene Ligand for Oxygen Imaging of Deeper Tissues In Vivo

In vivo O2 imaging in hepatic tissues by phosphorescence lifetime imaging microscopy using Ir(III) complexes as intracellular probes

Chemiluminescent 1,2‐Dioxetane Iridium Complexes for Near‐Infrared Oxygen Sensing

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