Viscosity Probe Research Articles

Mitochondrial viscosity probes:iridium(III) complexes induce apoptosis in HeLa cells.

Mitochondrial viscosity has emerged as a promising biomarker for diseases such as cancer and neurodegenerative disorders, yet accurately measuring viscosity at the subcellular level remains a significant challenge. In this study, we synthesized and characterized three cyclometalated iridium(III) complexes (Ir1-Ir3) containing 5-fluorouracil derivatives asligands. Among these, Ir1selectively induced apoptosis in HeLa cells by increasing mitochondrial production of reactive oxygen species (ROS), which triggered a cascade of events leading to mitochondrial dysfunction. Additionally, the fluorescence lifetime of Ir1demonstrated high sensitivity to intracellular viscosity changes, enabling real-time fluorescence lifetime imaging microscopy (FLIM) of cellular micro-viscosity during apoptosis. These findings underscore the potential of cyclometalated Ir(III) complexes forboth therapeutic and diagnostic applications at the subcellular level.

A novel fluorescent probe for viscosity and polarity detection in real tobacco root cells and biological imaging.

The disruption of lipid droplet function is associated with the pathogenesis of various diseases. Clarifying the response behavior of lipid droplets to the microenvironment at the cellular level is of great significance. Plant lipids not only exist in phospholipids in cell membranes, but also in aromatic essential oils. Monitoring the level of lipid droplets in plant cells using fluorescent probes provides a simple method for screening lipid-rich varieties. We synthesized a polarity-viscosity responsive coumarin fluorescent probe, Cou-CN, which achieved sensitive detection of polarity and viscosity in dilute solution environments by constructing this simple probe with ICT and TICT properties and verifying it using Gaussian computational simulation. Cou-CN exhibited good lipid droplet illumination effects in HepG2 cells with a correlation coefficient of 0.92 compared to the commercial lipid droplet dye BODIPY. Additionally, co-staining the probe with the lipophilic commercial dye Nile Red in tobacco root stem seedling cells resulted in a high correlation coefficient of 0.9.

High-fidelity imaging of drug-induced acute gastritis by using a fluorescent and photoacoustic dual-modal probe with good stability in stomach acid

In consideration of deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-modal probes are much more desirable. However, dual-modal imaging of gastritis using molecular probes remains a challenge due to the harsh gastric acid environment in the stomach. Based on the positive correlation between gastritis and cell viscosity, stomach acid-stable and viscosity-activated probes could potentially diagnose gastritis. As a proof of concept, herein, a fluorescent and photoacoustic dual-modal probe (named WSP-1) is revealed for the imaging of drug-induced acute gastritis in vivo. WSP-1 exhibits viscosity-dependent fluorescence emission and photoacoustic signals. A rotatable C–C single bond is incorporated into the D-π-A structure of WSP-1, which could facilitate the formation of the twisted intramolecular charge transfer (TICT) state in a low-viscosity environment (weak fluorescence/PA signal) and the intramolecular charge transfer (ICT) state in a high-viscosity environment (strong fluorescence/PA signal). WSP-1 has demonstrated the capability to target mitochondria and can be utilized to monitor the viscosity enhancement of cells during inflammation. Most importantly, WSP-1 exhibits good optical and structural stability in gastric acid. By leveraging these desirable features of WSP-1, we have achieved fluorescent and 3D photoacoustic in situ imaging of drug-induced acute gastritis following oral administration of WSP-1.

An insight into the role of ESIPT/TICT-based antioxidant flavone analogues in fluoro-probing diabetes-induced viscosity changes: a unified experimental and theoretical endeavour.

Potent antioxidants, like 3-hydroxy flavones, attracted considerable attention due to their excited state intramolecular proton transfer (ESIPT)-based fluorescence behaviour. This article is an interesting demonstration of a series of synthetic 3-hydroxy flavone analogues having high antioxidant activity as molecular rotor-like viscosity probes. Among these flavone analogues, 4'-N,N-dimethylamino-3-hydroxy flavone (3) is the most potent one, showing the twisted intramolecular charge transfer (TICT)-dependent fluoroprobing activity toward the blood viscosity changes associated with diabetes and free fatty acids (FFA)-induced nuclear viscosity changes of MIN6 cells. The TICT dynamics of (3), which instigates its viscosity probing activity, was comprehended with the help of DFT-based computational studies. Abnormal cellular viscosity changes are the pathological traits for various diseases, and non-toxic flavone-based viscosity probes can be useful for diagnosing such pathological conditions.

A golgi targeting viscosity rotor for cancer diagnosis in living cells and tissues

Unveiling the intricate relationship between cancer and Golgi viscosity remains an arduous endeavor, primarily due to the lack of Golgi-specific fluorescent probes tailored for viscosity measurement. Considering this formidable obstacle, we have triumphed over the challenge by devising a bespoke Golgi-specific viscosity probe, aptly named GOL-V. This ingenious innovation comprises the viscosity rotor BODIPY intricately tethered to the Golgi-targeting moiety benzsulfamide. GOL-V exhibits remarkable sensitivity to fluctuations in viscosity, the fluorescence intensity of GOL-V increased 114-fold when the viscosity value was increased from 2.63 to 937.28 cP. Owing to its remarkable capacity to suppress the TICT state under conditions of heightened viscosity. Moreover, its efficacy in sensitively monitoring Golgi viscosity alterations within living cells is also very significant. Astonishingly, our endeavors have culminated in not only the visualization of Golgi viscosity at the cellular and tissue levels but also in the clinical tissue samples procured from cancer patients. Harnessing the prowess of GOL-V, we have successfully demonstrated that Golgi viscosity could serve as a discerning marker for detecting the presence of cancer. The convergence of these exceptional attributes firmly establishes GOL-V as an immensely potent instrument, holding immense potential in the realm of cancer diagnosis.

Three-channel fluorescent probe for real-time monitoring mitochondrial viscosity during mitophagy and visualizing ONOO-/SO2 in rheumatoid arthritis mice

ONOO- and SO2 are important microenvironment parameters in organisms, the intracellular levels of ONOO- and SO2 are abnormal in rheumatoid arthritis (RA) mice. Mitophagy plays a key role in maintaining mitochondrial quality and quantity, and viscosity monitoring is a crucial aspect of real-time visualization of mitophagy. Therefore, a mitochondria-targeting three-channel fluorescent probe HCPVP was first developed for the detection of ONOO-/SO2 and viscosity. HCPVP can sensitively detect ONOO- (514 nm) and SO2 (674 nm) change with different channels, meanwhile display turn-on fluorescence at 678 nm as the amount of glycerol increased. The fluorescence imaging of cells showed that HCPVP was able to better target mitochondria, monitor ONOO-/SO2 changes, and visualize the mitophagy process. HCPVP has been successfully used for monitoring ONOO- and SO2 in RA mice model, providing the early image of RA with the aid of the potential biomarkers ONOO- and SO2. More importantly, HCPVP could evaluate the response of the RA treatment with impressive results, which held the potential for assessing treatment and drug screening for RA.

A Red-Emission Fluorescent Probe with Large Stokes Shift for Detection of Viscosity in Living Cells and Tumor-Bearing Mice.

Abnormal viscosity is closely related to the occurrence of many diseases, such as cancer. Therefore, real-time detection of changes in viscosity in living cells is of great importance. Fluorescent molecular rotors play a critical role in detecting changes in cellular viscosity. Developing red emission viscosity probes with large Stokes shifts and high sensitivity and specificity remains an urgent and important topic. Herein, a novel viscosity-sensitive fluorescent probe (TCF-VIS1) with a large stokes shift and red emission was prepared based on the 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) skeleton. Due to intramolecular rotation, the probe itself does not fluorescence at low viscosity. With the increase in viscosity, the rotation of TCF-VIS1 is limited, and its fluorescence is obviously enhanced. The probe has the advantages of simple preparation, large Stokes shift, good sensitivity and selectivity, and low cytotoxicity, which make it successfully used for viscosity detection in living cells. Moreover, TCF-VIS1 showed its potential for cancer diagnosis at the cell level and in tumor-bearing mice by detecting viscosity. Therefore, the probe is expected to enrich strategies for the detection of viscosity in biological systems and offer a potential tool for cancer diagnosis.

Design and Screening of Fluorescent Probes Based upon Hemicyanine Dyes for Monitoring Mitochondrial Viscosity in Living Cells.

Viscosity, at the subcellular level, plays a crucial role as a physicochemical factor affecting microenvironment homeostasis. Abnormal changes in mitochondrial viscosity often lead to various diseases in the organism. Based on the twisted intramolecular charge transfer mechanism, four hemicyanine dye fluorescent probes (HT-SA, HT-SA-S, HT-Bzh, and HT-NA) were designed and synthesized for viscosity response. The single bond between the nitrogen-containing heterocycle and the carbon-carbon double in the structure of the probe bond served as the viscosity response site. Finally, the probe HT-Bzh was screened as the optimal mitochondrial viscosity probe according to its responsiveness, targeting, and interference resistance. The fluorescence intensity of the probe HT-Bzh increased 22-fold when the viscosity was increased from 13.75 to 811.2 cP. In summary, all four viscosity probes we have developed can be used in different applications depending on the external environment, providing a valuable reference for the design of potential tools to address viscosity monitoring in biological systems.

Rational design of a red-emission fluorescent probe for imaging mitochondrial viscosity and fatty liver tissues

Abnormal mitochondrial viscosity is closely associated with various diseases. Thus, it is imperative to design and synthesized fluorescent probes for monitoring changes in mitochondrial viscosity. In this work, two series of fluorescence probes with triphenylamine unit and 2-hydroxyphenylbenzothiazole unit respectively were constructed. The impact of varying chain lengths on the photophysical properties of these probes was investigated. The results indicated that probe TPAC12 with dodecane group exhibited the largest fluorescence enhancement. The results of cell imaging experiments demonstrated that all these probes exhibited specific targeting towards mitochondria and were not influenced by changes in mitochondrial membrane potential. Additionally, probe TPAC12 facilitated the monitoring of viscosity alterations within mitochondria. Importantly, probe TPAC12 has been effectively utilized for the identification of both fatty liver and normal liver tissues. These results suggested that probe TPAC12 holds great potential as a valuable tool for detecting mitochondrial viscosity in biological systems.

Electromagnetically spinning viscometer designed for measurement of low viscosity in low shear rate region

The electromagnetically spinning method for measurement of fluid viscosity was improved to obtain accurate values of low viscosity in the low shear rate region. Harmful effects derived from the mechanical friction to the smooth rotation of the rotor are thoroughly eliminated by employing a viscosity probe suspended by a thin metal wire. In our previous study, the motion of the meniscus of the sample surface also acted as a troublesome resistant torque for probe rotation, which was addressed by employing a sandwiched structure of the disk probe between the bottom and top plates. The measurements were carried out in two procedures. In the freely oscillating operation, we could measure the viscosity of the atmosphere with a viscosity of approximately 1/100 of that of water. The second type of quasi-steady measurement enabled a measurement of pure water in the range of shear deformation rates smaller than 1 s−1.

Mechanism study of the molluscicide candidate PBQ on Pomacea canaliculata using a viscosity-sensitive fluorescent probe

PBQ [1-(4-chlorophenyl)-3-(pyridin-3-yl)urea], an enormous potent molluscicide, showed excellent Pomacea canaliculata (P. canaliculata) control activity and low toxicity for other aquatic organisms, but its snail-killing mechanisms are still not fully understood. We employed an optical method to elucidate PBQ action via a novel fluorescent viscosity probe, NCV. As the viscosity in the test solutions increased, compared with that in pure ethanol, a 54-fold fluorescence intensity enhancement of NCV was observed in 310 cP of 90% glycerol. Furthermore, NCV successfully exhibited a selective fluorescence response towards monensin-induced cellular viscosity changes in HepG2 cells. The liver, stomach, and foot plantar of the tested snails were frozen and sectioned for fluorescent imaging experiments after the treatment with different PBQ concentrations over various times. A significant fluorescent increase in the snail's liver was observed upon exposure to 0.75 mg/L PBQ for 72 h, which highlighted an increase in viscosity. Hematoxylin and eosin (HE) staining further supported PBQ-induced liver damage with a viscosity increase in P. canaliculata. Our study provides a new rapid optical visualization method to study the killing mechanisms of PBQ and may help discover new chemicals that control snail populations.

Golgi-targeting viscosity probe for the diagnosis of Alzheimer’s disease

Early diagnosis and intervention of Alzheimer’s disease (AD) are particularly important to delay the pathological progression. Although fluorescent probes have been widely employed for investigating and diagnosing AD, their biological applications are significantly restricted due to the low penetration ability of the blood–brain barrier (BBB) in vivo. In this study, we reported the first Golgi-targeted two-photon (TP) fluorescent probe, DCM-DH, for detecting viscosity in the Golgi apparatus. The probe was rationally designed to exhibit superior analytical performance including high sensitivity, specific Golgi-targeting, efficient BBB penetration ability, and deep tissue penetration (247 μm) in the brains of AD model mice. Using the probe, we demonstrated that the fluorescence intensity in the human liver cancer cell (HepG2 cells) was higher than that of human normal liver cell (LO2 cells), and the brain viscosity of AD model mice increased significantly. We anticipate that this competent tool could be easily extended to other AD biomarkers for fundamental research on this detrimental disease.

Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

Quadrupolar, Highly Polarized Dyes: Emission Dependence on Viscosity and Selective Mitochondria Staining.

Quadrupolar A-D-A-type 1,4-dihydropyrrolo[3,2-b]pyrroles (DHPPs) bearing pyridinium and quinolinium substituents emit in the 500-600 nm region. The enhancement of electronic communication between the electron-rich heterocyclic core and electron-deficient peripheral substituents turned out to be crucial for achieving emission enhancement in viscous media. DHPP bearing two 4-pyridinium substituents has optical brightness 34,000 in glycerol and only 700 in MeOH, as evidenced by measurements of the emission intensity and fluorescence lifetimes in a series of polar solvents. Such behavior makes it an excellent candidate for viscosity probes in fluorescence microscopy, as demonstrated by the fluorescence imaging of H9C2 cardiomyocytes.

Fluorescent probes based on quinoline and naphthidine derivatives with NIR and AIE properties for real-time monitoring mitochondrial viscosity during mitophagy

As a special form of autophagy, mitophagy is a pivotal mechanism governing cellular metabolism and physiology. Viscosity monitoring is an important aspect for real-time visualization of the mitophagy process. Hence, the development of high-performance viscosity probes is crucial for investigating dynamic pathological processes related to mitophagy. This study presents the discovery of mitochondria near-infrared and aggregation-induced emission probes with neutral structure. Probes 1a-1b were connected quinoline/naphthidine malononitrile and coumarin units with a double bond, the absorption maxima were at 433–471 nm; emission maxima were at 605–720 nm with large Stokes shifts of 170–279 nm in solvents of different polarity. As the environmental viscosity increases from 0.89 cP to 856 cP, the fluorescence intensity of probe 1a and probe 1b is enhanced by 418-fold and 769-fold, respectively, which due to the restricted rotation and inhibited twisted intramolecular charge transfer in high viscosity systems. In addition to excellent NIR, hypotoxicity, and mitochondrial targeting capabilities, probes 1a-1b were successfully applied to detect changes in mitochondrial viscosity during starvation or rapamycin-induced mitophagy. These remarkable features make probes 1a-1b as promising candidates for investigating dynamic pathological processes related to mitophagy with significant potential for biological applications.

A near-infrared fluorescent probe for viscosity: Differentiating cancer cells from normal cells and dual-modal imaging in tumor mice

As a basic parameter of the intracellular microenvironment, viscosity is closely related to the development of cancer. Thus, it is necessary to utilize a sensitive tool to visualize the viscosity in tumor cells and mice, which is helpful for the diagnosis of cancer. Herein, a novel dual-modal probe (IX-V) that has a near-infrared fluorescence (NIRF) and photoacoustic (PA) response to viscosity is synthesized. In low viscosity media, the probe has no fluorescence. With the increase of viscosity, the fluorescence is produced in the near-infrared region due to the inhibition of the TICT process. At the same time, the probe shows different photoacoustic (PA) signals in different viscosity media. Most notably, the viscosity in tumor cells has been imaged successfully by the application of IX-V, and the probe can effectively distinguish cancer cells from normal cells co-cultured in one dish by the difference of fluorescence intensity. In addition, the probe has been used for dual-modal imaging (NIRF and PA) of viscosity in tumor mice, which provides a tool for exploring the relationship between viscosity and diseases. That is to say, IX-V can achieve complementary imaging effects and has great application prospects in the tumor diagnosis.

A new near-infrared ratiometric fluorescent probe using conjugated dicyanoisophorone and quinoline with double vinylene linkers for sensing of pH and its application

pH plays a crucial role in multiple biological processes, therefore, the development of pH imaging and measurement using the fluorescent probes in biological systems is highly active and has an urgent demand. In this work, a new ratiometric near-infrared (NIR) fluorescent probe DCIQ based on conjugated dicyanoisophorone and quinoline with double vinylene linkers was obtained for pH sensing. The remote conjugated quinoline and middle phenol used as an acceptor for protons may induce dual-modal colorimetric and fluorescence changes as a function of tiny variations in pH in the range of 6–8. Compared to previously reported probes, the proposed DCIQ probe was advantageous in terms of near-infrared emission signal (734 nm), large Stockes shift (173 nm), high selectivity, and good sensitivity. In addition, DCIQ could be as potential probe for viscosity by the fluorescence change. Moreover, the DCIQ-immobilized test papers exhibited reversible colorimetric changes as a function of variations in the environmental acid/base (>4 cycles) through naked-eye colorimetric detection. The desirable pKa (7.24) indicated that DCIQ probe could be used as a molecular tool for readily entering living cells with low cytotoxicity. Importantly, the DCIQ probe was successfully demonstrated for real-time detection of pH fluctuation in HeLa cells through ratiometric fluorescence images.

Rational Design of Near-Infrared Fluorescent Probes for Accurately Tracking Lysosomal Viscosity with Allyl Snchoring Si-Rhodamine.

The abnormal microenvironment parameter, viscosity, is closely connected with various diffusion processes, signal transduction, molecule interactions, and various diseases. It is greatly significant to design viscosity-dependent near-infrared (NIR) small molecule fluorescence probes for visualizing biological processes or diagnosing diseases. Herein, through the stepwise modulating structure of the silicon-rhodamine fluorophore (SR), we report three viscosity probes with allyl or methyl group as rotors, named SR-T-Al, SR-S-Al, and SR-T-Me. Among them, SR-T-Al demonstrates better viscosity responsibility from 1.0 to 1410.4 cP of viscosity. Therefore, the probe of SR-T-Al is successfully applied to sensitively monitor lysosome microscopic viscosity changes of living cells induced by oxygen stress. What's more, based on its advantages in NIR emission (669 nm) and large Stokes shift (201 nm), we also use it to image variations of viscosity in an acute hepatitis mouse induced by carbon tetrachloride. Both time and concentration-dependent induction models display the great ability of SR-T-Al to detect viscosity alteration. All the experimental results indicated that this allyl-rotor-based NIR viscosity probe could provide a general platform to monitor abnormal physiological processes and diseases relating to viscosity.

Synergistic effects of multiple rotors and hydrogen-bond interactions lead to sensitive near-infrared viscosity probes for live-cell microscopy

Synergistic effects of multiple rotors and hydrogen-bond interactions lead to sensitive near-infrared viscosity probes for live-cell microscopy

Multifunctional Mitochondria-Targeting Near-Infrared Fluorescent Probe for Viscosity, ONOO-, Mitophagy, and Bioimaging.

Irregularities in mitochondrial viscosity and peroxynitrite (ONOO-) concentration can lead to mitochondrial dysfunction. It is still a great challenge to develop near-infrared (NIR) fluorescent probes to simultaneously detect viscosity, endogenous ONOO-, and mitophagy. Herein, a multifunctional mitochondria-targeting NIR fluorescent probe P-1 was first synthesized for simultaneously detecting viscosity, ONOO-, and mitophagy. P-1 used quinoline cations as a mitochondrial targeting moiety, arylboronate as an ONOO- responsive group, and detected the change of viscosity by the twisted internal charge transfer (TICT) mechanism. The probe has an excellent response to the viscosity during inflammation by lipopolysaccharides (LPSs) and mitophagy induced by starvation at 670 nm. The viscosity changes of the probe induced by nystatin in zebrafish showed that P-1 was able to detect microviscosity in vivo. P-1 also showed good sensitivity with a detection limit of 6.2 nM for ONOO- detection and was successfully applied to the endogenous ONOO- detection in zebrafish. Moreover, P-1 has the ability to distinguish between cancer cells and normal cells. All of these features make P-1 a promising candidate to detect mitophagy and ONOO- -associated physiological and pathological processes.