Development of a Series of Practical Fluorescent Chemical Tools To Measure pH Values in Living Samples

Takahashi, Shodai; Kagami, Yu; Hanaoka, Kenjiro; Terai, Takuya; Komatsu, Toshimitsu; Ueno, Takahiro; Uchiyama, Masanobu; Koyama-Honda, Ikuko; Mizushima, Noboru; Taguchi, Tomohiko; Arai, Hiroyuki; Nagano, Tetsuo; Urano, Yasuteru

doi:10.1021/jacs.8b00277

Cited by 124 publications

(71 citation statements)

References 46 publications

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“…The intravenous administration of Dex-Me-pEPPR showed a more acidic value in the tumor region compared to healthy region (Fig. 14), in good agreement with the pH values measured using a pH electrode [140].…”

Section: Optical Imagingsupporting

confidence: 81%

Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH

Anemone

Consolino

Arena

et al. 2019

Cancer Metastasis Rev

118

110

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Cancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1α, from mitochondrial oxidative phosphorylation to increased glycolysis, regardless of oxygen availability (Warburg effect). The constitutive upregulation of glycolysis leads to an overproduction of acidic metabolic products, resulting in enhanced acidification of the extracellular pH (pHe~6.5), which is a salient feature of the tumor microenvironment. Despite the importance of pH and tumor acidosis, there is currently no established clinical tool available to image the spatial distribution of tumor pHe. The purpose of this review is to describe various imaging modalities for measuring intracellular and extracellular tumor pH. For each technique, we will discuss main advantages and limitations, pH accuracy and sensitivity of the applied pH-responsive probes and potential translatability to the clinic. Particular attention is devoted to methods that can provide pH measurements at high spatial resolution useful to address the task of tumor heterogeneity and to studies that explored tumor pH imaging for assessing treatment response to anticancer therapies.

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Section: Optical Imagingsupporting

confidence: 81%

Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH

Anemone

Consolino

Arena

et al. 2019

Cancer Metastasis Rev

118

110

View full text Add to dashboard Cite

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“…Hanaoka, Urano et al synthesized asymmetric phospharhodamines bearing a piperazine ring as a ratiometric pH imaging probe based on NIR fluorescence (compound 16 , Figure ). The authors modulated the p K a of the phospharhodamines for in vivo measurements by incorporating different substituents at the piperazine moieties; i.e.…”

Section: Phosphorus Heteroarenes: the Originmentioning

confidence: 99%

From Phosphaphenalenes to Diphosphahexaarenes: An Overview of Linearly Fused Six‐Membered Phosphorus Heterocycles

2019

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The chemistry of linearly fused systems based on sixmembered phosphorus heterocycles is currently experiencing an astonishing evolution. Even though the phosphorus analogs of naphthalene and anthracene were first synthesized in the late 1960s, laterally fused phosphorus heterocycles have recently demonstrated outstanding performances as biomarkers, [a] Scheme 2. Synthetic route to afford diphosphahexaarenes: a) CsF, Pd(PPh 3 ) 4 , CuI, 50°C/(8-bromonaphthalen-1-yl)tributylstannane; b) 1. tBuLi, -78°C, 2. PhPCl 2 , 3. H 2 O 2 , 0°C.

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“…Therefore, developing an ultrasensitive pH sensor has extremely high practical importance. [27,28] Here, a polarizable azobenzene (azo) chromophore was employed to impose a dipole moiety via the protonation process of molecule. [29] Azo is a classic pH indicator dye, [30,31] but its application is severely limited due to its poor water solubility and serious aggregations after protonation.…”

Section: Knowledge Of Interfacial Interactions Between Analytes and Fmentioning

confidence: 99%

Synergy of Ionic and Dipolar Effects by Molecular Design for pH Sensing beyond the Nernstian Limit

et al. 2019

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interface generates original signal and plays a crucial role in the sensing process. In ion sensors, the interaction between ions and ion receptors can lead to accumulation of interfacial charges, thereby causing an interfacial potential change that can be electronically readout. [3] A versatile sensing platform can also be designed by functionalizing the sensor surface with self-assembled organic monolayers (SAMs), which offers the possibility to tailor the chemical and/or physical interactions of the sensor surface with analytes. These interfacial interactions can generate additional changes in surface dipoles and/or charges on the sensing surface, [4,5] which can in turn affect the electrical properties of the surface and tune the sensitivity. [6][7][8] It can be emphasized that both surface charge and dipole play an equally important role in establishing the surface equilibrium state. The dipole effect can be engineered in a controllable and systematic way. Therefore, modulating the molecular dipole moment to enhance device performance holds promises in numerous applications. [9][10][11] However, the molecular dipole effect is strongly dependent on multiple parameters in practice, such as dipole orientation, distribution, and packing density of each molecule within the SAM. [12,13] These parameters are strongly inter-correlated. For example, increasing the dipole moment of the surface immobilized molecules can enhance the electrostatic repulsions between neighboring dipoles, influence the packing density, and even change the configuration of the SAM. Thus, in order to engineer the interfacial dipole in a controllable manner, a rational design of the system is needed.Since the dipole moment originates from the charge separation between atoms due to their difference in electronegativity, changing the electronegativity on the molecular substituent can be an efficient way to modulate the molecular dipole. A dipole moment can also be formed by ion pair of cation and anion, [14,15] which can be embodied by a well-known phenomenon that the electrostatic attraction between cations and anions can lead to a significant change in surface wettability. [16,17] This ionic dipole is strongly dependent on the polarizability of the ionic pair, and is affected by the properties of the ions such as ionic radius and hydration energy. [18,19] Therefore, artificial designs to form ion pairs can be an alternative to create dipoles on the sensing surface for modulation of its sensitivity. With proper molecular Knowledge of interfacial interactions between analytes and functionalized sensor surfaces, from where the signal originates, is key to the development and application of electronic sensors. The present work explores the tunability of pH sensitivity by the synergy of surface charge and molecular dipole moment induced by interfacial proton interactions. This synergy is demonstrated on a silicon-nanoribbon field-effect transistor (SiNR-FET) by functionalizing the sensor surface with properly designed chromophore molecules. The ch...

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Development of a Series of Practical Fluorescent Chemical Tools To Measure pH Values in Living Samples

Cited by 124 publications

References 46 publications

Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH

Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH

From Phosphaphenalenes to Diphosphahexaarenes: An Overview of Linearly Fused Six‐Membered Phosphorus Heterocycles

Synergy of Ionic and Dipolar Effects by Molecular Design for pH Sensing beyond the Nernstian Limit

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