Phosphorescent NIR emitters for biomedicine: applications, advances and challenges

Tunik, Sergey P.; Chelushkin, Pavel S.; Shakirova, Julia R.; Kritchenkov, Ilya S.; Baigildin, Vadim A.

doi:10.1039/d1dt03077a

Cited by 36 publications

(32 citation statements)

References 213 publications

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“…Therefore, it is necessary either to minimize the probe lifetime sensitivity to O 2 (by the chromophore shielding with bulky ligands, its encapsulation into polymeric nanoparticles, etc. [ 17 ]) or to use the probe simultaneously with an oxygen sensor to correct the lifetime data for the oxygen quenching effect; (b) It is also necessary to evaluate and minimize the other distorting effects of such factors as media viscosity, interaction with biomolecules and metal ions; (c) The processing of multiexponential decay curves requires high emission intensity to obtain reliable statistics of the decay photons and high precision lifetime data. Thus, increase in the sensor emission quantum yield is also highly desirable.…”

Section: Resultsmentioning

confidence: 99%

“…On the contrary, transition metal complexes usually show high photostability, long-lived emission with large Stokes shift. The latter two characteristics allow cutting off the sample autofluorescence, which helps to increase sensor sensitivity and the precision of the measurements [ 17 ]. The most studied phosphorescent sensors are platinum-group metal complexes, in particular cyclometalated Ir(III) compounds [ 18 , 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we focused on synthesis and investigation of the [Ir( N^C ) 2 ( L^L )] complexes bearing phenantroimidazole-based N^C ligand that contains nucleophilic nitrogen center potentially prone to protonation, thus giving a sensory response onto pH variations. Since insolubility in aqueous media is the main disadvantage of the majority of the typical cyclometalated iridium complexes suggested for pH-sensing in bioimaging [ 17 ], we also introduced -SO 3 Na and -COOH groups into the lateral L^L -ligand to increase hydrophilicity of the complex as a whole. The complexes obtained demonstrate phosphorescence in the yellow-orange region of the visible spectra.…”

Section: Introductionmentioning

confidence: 99%

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pH-Responsive N^C-Cyclometalated Iridium(III) Complexes: Synthesis, Photophysical Properties, Computational Results, and Bioimaging Application

et al. 2021

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Herein we report four [Ir(N^C)2(L^L)]n+, n = 0,1 complexes (1–4) containing cyclometallated N^C ligand (N^CH = 1-phenyl-2-(4-(pyridin-2-yl)phenyl)-1H-phenanthro[9,10-d]imidazole) and various bidentate L^L ligands (picolinic acid (1), 2,2′-bipyridine (2), [2,2′-bipyridine]-4,4′-dicarboxylic acid (3), and sodium 4,4′,4″,4‴-(1,2-phenylenebis(phosphanetriyl))tetrabenzenesulfonate (4). The N^CH ligand precursor and iridium complexes 1–4 were synthesized in good yield and characterized using chemical analysis, ESI mass spectrometry, and NMR spectroscopy. The solid-state structure of 2 was also determined by XRD analysis. The complexes display moderate to strong phosphorescence in the 550–670 nm range with the quantum yields up to 30% and lifetimes of the excited state up to 60 µs in deoxygenated solution. Emission properties of 1–4 and N^CH are strongly pH-dependent to give considerable variations in excitation and emission profiles accompanied by changes in emission efficiency and dynamics of the excited state. Density functional theory (DFT) and time-dependent density functional theory (TD DFT) calculations made it possible to assign the nature of emissive excited states in both deprotonated and protonated forms of these molecules. The complexes 3 and 4 internalize into living CHO-K1 cells, localize in cytoplasmic vesicles, primarily in lysosomes and acidified endosomes, and demonstrate relatively low toxicity, showing more than 80% cells viability up to the concentration of 10 µM after 24 h incubation. Phosphorescence lifetime imaging microscopy (PLIM) experiments in these cells display lifetime distribution, the conversion of which into pH values using calibration curves gives the magnitudes of this parameter compatible with the physiologically relevant interval of the cell compartments pH.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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pH-Responsive N^C-Cyclometalated Iridium(III) Complexes: Synthesis, Photophysical Properties, Computational Results, and Bioimaging Application

et al. 2021

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“…Recently, a new class of phosphorescent reporters detected using a fluorescent microscope was developed. The photophysical properties of some of these O 2 sensors have been recently reviewed and go beyond the scope of this review [ 46 , 47 ].…”

Section: Detection Of Hypoxia In Vitromentioning

confidence: 99%

Detection of Hypoxia in Cancer Models: Significance, Challenges, and Advances

Godet

Doctorman

et al. 2022

Cells

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The rapid proliferation of cancer cells combined with deficient vessels cause regions of nutrient and O2 deprivation in solid tumors. Some cancer cells can adapt to these extreme hypoxic conditions and persist to promote cancer progression. Intratumoral hypoxia has been consistently associated with a worse patient prognosis. In vitro, 3D models of spheroids or organoids can recapitulate spontaneous O2 gradients in solid tumors. Likewise, in vivo murine models of cancer reproduce the physiological levels of hypoxia that have been measured in human tumors. Given the potential clinical importance of hypoxia in cancer progression, there is an increasing need to design methods to measure O2 concentrations. O2 levels can be directly measured with needle-type probes, both optical and electrochemical. Alternatively, indirect, noninvasive approaches have been optimized, and include immunolabeling endogenous or exogenous markers. Fluorescent, phosphorescent, and luminescent reporters have also been employed experimentally to provide dynamic measurements of O2 in live cells or tumors. In medical imaging, modalities such as MRI and PET are often the method of choice. This review provides a comparative overview of the main methods utilized to detect hypoxia in cell culture and preclinical models of cancer.

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“…In this respect, the application of luminescent molecular and nanosized sensors based on phosphorescent emitters has an undoubted advantage, because in the presence of molecular oxygen their emission is effectively quenched, providing clearly detectable variations in emission intensity along with the quantitative dependence of an excited state lifetime on oxygen concentration. It should be noted that, in recent years, the advanced technique of phosphorescent lifetime imaging (PLIM) has found a wide range of applications as an important instrument for monitoring the oxygen concentration in biological systems [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Unlike the oxygen sensing methods based on quantitative considerations, PLIM measurements do not need external or internal standards and the sensor response depends neither on the local sensor concentration nor on the optical properties of the sample under study that exclude the distortion of the results by these biasing factors [ 5 , 7 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Novel NIR-Phosphorescent Ir(III) Complexes: Synthesis, Characterization and Their Exploration as Lifetime-Based O2 Sensors in Living Cells

et al. 2022

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A series of [Ir(N^C)2(N^N)]+ NIR-emitting orthometalated complexes (1–7) has been prepared and structurally characterized using elemental analysis, mass-spectrometry, and NMR spectroscopy. The complexes display intense phosphorescence with vibrationally structured emission bands exhibiting the maxima in the range 713–722 nm. The DFT and TD DFT calculations showed that the photophysical characteristics of these complexes are largely determined by the properties of the metalating N^C ligands, with their major contribution into formation of the lowest S1 and T1 excited states responsible for low energy absorption and emission, respectively. Emission lifetimes of 1–7 in degassed methanol solution vary from 1.76 to 5.39 µs and show strong quenching with molecular oxygen to provide an order of magnitude lifetime reduction in aerated solution. The photophysics of two complexes (1 and 7) were studied in model physiological media containing fetal bovine serum (FBS) and Dulbecco’s Modified Eagle Medium (DMEM) to give linear Stern-Volmer calibrations with substantially lower oxygen-quenching constants compared to those obtained in methanol solution. These observations were interpreted in terms of the sensors’ interaction with albumin, which is an abundant component of FBS and cell media. The studied complexes displayed acceptable cytotoxicity and preferential localization, either in mitochondria (1) or in lysosomes (7) of the CHO-K1 cell line. The results of the phosphorescence lifetime imaging (PLIM) experiments demonstrated considerable variations of the sensors’ lifetimes under normoxia and hypoxia conditions and indicated their applicability for semi-quantitative measurements of oxygen concentration in living cells. The complexes’ emission in the NIR domain and the excitation spectrum, extending down to ca. 600 nm, also showed that they are promising for use in in vivo studies.

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Phosphorescent NIR emitters for biomedicine: applications, advances and challenges

Abstract: Application of NIR (near-infrared) emitting transition metal complexes in biomedicine is a rapidly developing area of research. Emission of this class of compounds in the “optical transparency windows” of biological...

Cited by 36 publications

References 213 publications

pH-Responsive N^C-Cyclometalated Iridium(III) Complexes: Synthesis, Photophysical Properties, Computational Results, and Bioimaging Application

pH-Responsive N^C-Cyclometalated Iridium(III) Complexes: Synthesis, Photophysical Properties, Computational Results, and Bioimaging Application

Detection of Hypoxia in Cancer Models: Significance, Challenges, and Advances

Novel NIR-Phosphorescent Ir(III) Complexes: Synthesis, Characterization and Their Exploration as Lifetime-Based O2 Sensors in Living Cells

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