Fluorescent Probe Research Articles

Paclitaxel Inhibits Thyroid Cancer by Regulating AMPK/mTOR and Promoting Ferroptosis

Aim at probe into the mechanisms of paclitaxel inhibition in thyroid cancer. Cell viability was detected via CCK8 assay, KTC-1 proliferation, migration, invasion were detected via colony formation, wound healing as well as transwell assay. Flow cytometry measure the cell cycle and apoptosis, protein expression was detected with Western blot. Iron ions, GSH and MDA were detected by corresponding assay kits, respectively. ROS levels was detected with a fluorescence probe. KTC-1 cells viability decreased significantly when treated with 500 nM paclitaxel, and the proliferation, migration as well as invasion abilities were also significantly weakened. Moreover, paclitaxel induced KTC-1 cell mitosis arrest in G2/M phase to inhibited cell mitosis, and significantly increased the apoptosis. We also found paclitaxel treatment activated AMPK/mTOR signaling pathway, and iron ion, MDA as well as ROS level were significantly increased, while GSH level and expression of GPX4 protein was notably decreased in paclitaxel-treated KTC-1 cells. Our research shows that paclitaxel significantly inhibits the viability, proliferation, migration as well as invasion of KTC-1 cells via activating the AMPK/mTOR signaling pathway, and increase oxidative stress in KTC-1 cells, inducing ferroptosis in KTC-1 cells, providing new support for paclitaxel in the treatment of thyroid cancer.

A General Cyanine‐Based Platform for Designing Robust Dual‐Channel Near‐Infrared Fluorescent and Photoacoustic Probes

AbstractThe creation of versatile platforms for developing dual‐channel near‐infrared fluorescent (NIRF) and photoacoustic (PA) probes, especially those engineered to minimize channel crosstalk, is crucial for precise biomarker detection. However, such platforms remain scarce. To bridge this gap, this study introduces an innovative cyanine‐based platform, CySN. The CySN platform showcases remarkable wavelength‐shifting properties, including large fluorescent modality shift (68 nm) and PA modality shift (145 nm) after the decaging reaction. These substantial changes lead to an exceptionally high ratiometric NIRF change of 603‐fold and ratiometric PA change of 261‐fold. Leveraging the CySN platform, dual‐channel NIRF/PA probes have been successfully developed for detecting both small molecule biomarker (H2O2) and enzyme biomarker (esterase). These probes demonstrate the ability to detect their targets through dual‐channel NIRF/PA detection with high sensitivity and selectivity in vitro. Furthermore, the probes effectively harness NIRF signals to image target analytes in living cells. Notably, the probes demonstrate the capability to accurately diagnose tumors by detecting tumor markers (H2O2 and esterase), revealing a 3.6 to 7‐fold ratiometric PA enhancement over normal tissue. Therefore, the CySN platform holds the potential to further advance the development of dual‐channel NIRF/PA probes for biomolecule detection in disease diagnosis.

A novel tricyanofuran-based near-infrared fluorescent probe for rapid detection and discrimination of Cys/Hcy and GSH/H2S

A novel dual-emission responsive near-infrared fluorescent probe (2-OH-TCF-NBD) for the detection and discrimination of Cys/Hcy, GSH/H2S was developed on the basis of the conjugation of a tricyanofuran-based fluorophore (2-OH-TCF) and 4-chloro-7-nitrobenzofurazan (NBD-Cl). When the probe was added to the Cys/Hcy solution, it resulted in significant fluorescence enhancement at both 527 and 630 nm, while GSH/H2S induced major fluorescence emission only at 630 nm. The detection limits for Cys, Hcy, GSH, and H2S were determined to be 0.029, 0.020, 0.29, and 0.20 μM, respectively. Furthermore, the probe demonstrated some merits including easy preparation, rapid response time, and good anti-interference ability. The possible response mechanism was also proposed and validated by HPLC analysis of the reaction process. Therefore, the probe can be a potential tool for discriminating the detection of Cys/Hcy and GSH/H2S under physiological conditions.

Amphiphilic AIE Fluorescent Probe: A Dual-Functionality Strategy for Efficient Antibacterial Therapy Fluorescence Bioimaging against Staphylococcus aureus.

Drug-resistant bacteria present a grave threat to human health. Fluorescence imaging-guided photodynamic antibacterial therapy holds enormous potential as an innovative treatment in antibacterial therapy. However, the development of a fluorescent material with good water solubility, large Stokes shift, bacterial identification, and high photodynamic antibacterial efficiency remains challenging. In this study, we successfully synthesized an amphiphilic aggregation-induced emission (AIE) fluorescent probe referred to as NPTPA-QM. This probe possesses the ability to perform live-bacteria fluorescence imaging while also exhibiting antibacterial activity, specifically against Staphylococcus aureus (S. aureus). We demonstrate that NPTPA-QM can eliminate S. aureus at a very low concentration (2 μmol L-1). Moreover, it can effectively promote skin wound healing. Meanwhile, this NPTPA-QM exhibits an excellent imaging ability by simple mixing with S. aureus. In summary, this research presents a straightforward and highly effective method for creating "amphiphilic" AIE fluorescent probes with antibacterial properties. Additionally, it offers a rapid approach for imaging bacteria utilizing red emission.

Dissolved black nitrogen: an overlooked active nano-catalyst in the abiotic transformation of chlorophenols by sulfides in the subsurface water

The incomplete combustion of biomass and fossil fuels results in the formation of not only black carbon (BC) but also black nitrogen (BN), the dissolved fractions of which (i.e., DBC and DBN) are important components of dissolved organic matter pool. Relative to DBC, the activity and reactivity of DBN are much less understood. Here, we investigated the catalytic effect of DBN derived from N-enriched biomass in the abiotic transformation of chlorophenols by sulfides. The medium-temperature DBN (450 °C) exhibited 13–144% higher catalytic efficiency than other DBN samples and 9.3 times higher than its DBC counterpart. Both electron paramagnetic resonance spectra and fluorescent probe technique indicated that the attached sulfides contributed to the formation of reactive oxygen species (ROS) as the “primary” radicals by favoring electron transfer from DBN to chemisorbed oxygen, and then the generated ROS reacted with N-oxides in DBN to form reactive nitrogen species (RNS) as the “secondary” radicals. The contribution of RNS to the decay of 2-chlorophenol by DBN450 was up to 72%, much higher than that of ROS and non-radical mechanism. These findings suggest that the catalytic effect of DBN is distinct but no less significant than that of DBC to the abiotic transformation of micropollutants in water/soil systems.Graphical

Promotion and Detection of Cell-Cell Interactions through a Bioorthogonal Approach.

Manipulation of cell-cell interactions via cell surface modification is crucial in tissue engineering and cell-based therapy. To be able to monitor intercellular interactions, it can also provide useful information for understanding how the cells interact and communicate. We report herein a facile bioorthogonal strategy to promote and monitor cell-cell interactions. It involves the use of a maleimide-appended tetrazine-caged boron dipyrromethene (BODIPY)-based fluorescent probe and a maleimide-substituted bicyclo[6.1.0]non-4-yne (BCN) to modify the membrane of macrophage (RAW 264.7) and cancer (HT29, HeLa, and A431) cells, respectively, via maleimide-thiol conjugation. After modification, the two kinds of cells interact strongly through inverse electron-demand Diels-Alder reaction of the surface tetrazine and BCN moieties. The coupling also disrupts the tetrazine quenching unit, restoring the fluorescence emission of the BODIPY core on the cell-cell interface, and promotes phagocytosis. Hence, this approach can promote and facilitate the detection of intercellular interactions, rendering it potentially useful for macrophage-based immunotherapy.

Near-infrared lipid droplets polarity fluorescent probe for early diagnosis of nonalcoholic fatty liver disease

Nowadays, it has been proven that lipid droplets (LDs) not only maintain the fundamental cellular functions, but also play an essential role in the pathogenesis of numerous diseases. Non-alcoholic fatty liver disease (NAFLD) is among these diseases. In this work, we designed two polarity sensitive fluorescent probes TST and TSO with D-π-A-D structure by introducing different electron acceptor groups according to the low polarity of LDs. The experimental discovered that probe TST exhibited the characteristics of near-infrared emission, high selectivity towards polarity, large Stokes shift, rapid targeting ability of LDs, and robust wash-free biological imaging capability. Confocal images illustrated that probe TST has been successfully applied in monitoring LDs polarity during ferroptosis, as well as visualizing changes in LDs polarity at both tissue and organ levels in fatty liver conditions. With these exceptional properties, probe TST was anticipated to make further contributions to the field of LDs research.

Delineating a tailor-made fluorescent probe designed for the selective detection of tyrosinase.

A dicyanoisophorone based fluorescent probe (E)-2-(3-(4-hydroxystyryl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (DCIP-OH) was developed for the selective sensing of tyrosinase in apple extract and live cells. The probe was obtained by the condensation of 2-(3,5,5-trimethylcyclohex-2-en-1-ylidene)malononitrile with 4-hydroxybenzaldehyde. Upon interaction with tyrosinase, the probe exhibited absorbance switching from 417 nm to 357 nm, accompanied by a slight increase in absorption value and an isosbestic point observed at 373 nm. Additionally, a reduction in emission intensity at 592 nm was observed. Furthermore, we successfully employed the probe for sensing of tyrosinase in apple extract and conducted inhibition studies by using kojic acid. LOD was determined to be ~0.4 nM. Moreover, the biocompatible nature of DCIP-OH enabled its effective localization in epithelial-like melanoma cells, B16F10, where it demonstrated successful fluorescent probing of intracellular tyrosinase.

Highly-Selective fluorescent Fe3O4@PPy aptasensor

Label-free nucleic acid fluorescent probes are gaining popularity due to their low cost and ease of application. However, the primary challenges associated with label-free fluorescent probes stem from their tendency to interact with other biomolecules, such as RNA, proteins, and enzymes, which results in low specificity. In this work, we have developed a simple detection platform that utilizes Fe3O4@PPy in combination with a label-free nucleic acid probe, 1,1,2,2-tetrakis[4-(2-bromo-ethoxy)phenyl]ethene (TTAPE) or Malachite Green (MG), for highly selective detection of metal ions, acetamiprid, and thrombin. Fe3O4@PPy not only adsorbs aptamers through electrostatic interactions, π–π bonding, and hydrogen bonding, but also quenches the fluorescence of the TTAPE/MG. Upon the addition of target compounds, the aptasensor separates from Fe3O4@PPy through magnetic separation. Moreover, by changing different aptamers, the aptasensor was applied to detect metal ions, acetamiprid, and thrombin, with the turned-on photoluminescence (PL) emission intensity recorded and showing linearity to the concentrations of targets. The robustness of method was demonstrated by applying it to real samples, which included vegetables (for detecting acetamiprid with LODs of 0.02 and 0.04 ng/L), serum samples (for detecting thrombin with LODs of 5.5 and 4.3 nM), and water samples (for detecting Pb2+ with an LOD of 0.17 nM). Therefore, due to its impressive selectivity and sensitivity, the Fe3O4@PPy aptasensor could be utilized as a universal detection platform for various clinical and environmental applications.

Synthesis and application of a novel fluorescent probe based on benzothiazole for detection of hydrazine in real samples

ABSTRACT A novel fluorescence enhancement type probe 2-(1, 3-benzothiazol-2-yl)-5-(diethylamino)phenyl thiophene-2-carboxylate (PTN) for the detection of hydrazine (N2H4) was designed and synthesised. The fluorescence of the probe PTN solution increased dramatically upon the addition of N2H4 and its appearance changed from nearly colourless to dazzling blue. The simple structure and readily available fluorescent probe provide a novel approach for the quantitative detection of N2H4 in the linear range from 0 to 37.5 μM, with a detection limit down to 56 nM, fast response (within 5 min), strong anti-interference ability, easy operation (test paper), and a wide range of pH from 6 to 10. Furthermore, the probe PTN was able to detect N2H4 in actual water samples and image the exogenous N2H4 signal in colorimetric test strips and living zebrafish.

Design and application of Cd2+ polypeptide fluorescent probes based on Aggregation Induced Emission (AIE).

Cadmium is a toxic heavy metal, which is both an environmental pollutant, and a threat to human health. A fluorescent probe was developed to detect Cd2+ selectively, sensitively, and quickly. This study reports the successful development of a polypeptide fluorescent probe TPE-HC (TPE-His-Pro-Gly-Cys) which selectively detects Cd2+ by Aggregation-Induced Emission effect. After fluorescence excitation, Cd2+ can be effectively detected based on the change of fluorescence intensity. The detection limit of Cd2+ in buffer solution was determined to be 151 nM (R2 = 0.9933). This probe exhibits high sensitivity, high cell permeabilit y, and low biological toxicity, and can perform live cell imaging under biological conditions. This study indicates that TPE-HC can detect Cd2+ in biological environments.

An activated near-infrared mitochondrion-targetable fluorescent probe for rapid detection of NADH.

A novel NIR fluorescent probe based on quinoline-conjugated benzo[cd]indol dual-salt for NADH was developed. This probe swiftly detects and responds sensitively to both endogenous and exogenous NADH alterations, enabling imaging of NADH fluctuations in type II diabetic and AD model cells.

On-Site Quantitative Visualization of Singlet Oxygen in Crops via an Organic Small Molecule-Based Ratiometric Fluorescent Probe and a Mobile Fluorescence Analysis Device.

Singlet oxygen (1O2) plays imperative roles in a variety of biotic or abiotic stresses in crops. The change of its concentration within a crop is closely related to the crop growth and development. Accordingly, there is an urgent need to develop an efficient analytical method for on-site quantitative detection of 1O2 in crops. Here, we judiciously constructed a novel ratiometric fluorescent probe, SX-2, for the detection of 1O2 in crops. Upon treating with 1O2, probe SX-2 displayed highly selective ratiometric fluorescence response, which is favorable for the quantitative detection of 1O2. Concurrently, the fluorescence solution color of probe SX-2 was varied, obviously from blue to yellow, indicating that the probe is beneficial for on-site detection by the naked eye. Sensing reaction mechanism studies showed that the 2,3-diphenyl imidazole group in SX-2 could function as a new selective recognition group for 1O2. Probe SX-2 was utilized for the detection of photoirradiation-induced 1O2 and endogenous 1O2 in living cells. The changes in the 1O2 level in zebrafish were also tracked by fluorescence imaging. In addition, the production of 1O2 in crop leaves under a light source of different wavelengths was studied. The results demonstrated more 1O2 were produced under a light source of 365 nm. Furthermore, to achieve on-site quantitative detection, a mobile fluorescence analysis device has been made. Probe SX-2 and mobile fluorescence analysis device were capable of on-site quantitative detecting of 1O2 in crops. The method developed herein will be convenient for the on-site quantitative measurement of 1O2 in distinct crops.

Advances in preclinical approaches for intravesical therapy of bladder cancer.

The purpose of this review is to explore new strategies to treat bladder cancer. This article addresses challenges and opportunities in intravesical therapy of bladder cancer. The review examines the latest advances in the development of preclinical approaches for intravesical therapy of bladder cancer. It discusses strategies to improve drug delivery efficiency by using synthesized diverse carriers. Immunotherapy with protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride has been shown to be more effective than intravesical Bacillus Calmette-Guerin. Novel drug delivery systems such the urinary drug-disposing strategy and intravesical nanoparticle formulations improve the drug delivery efficiency while minimizing adverse reactions. Innovative imaging techniques using near-infrared fluorescence probes and multifunctional nano-transformers enable real-time detection and targeted therapy in bladder cancer treatment. Treatment of bladder cancer is clinically challenging. However, recent progress in drug delivery technologies shows promise. Optimizing these technologies helps improve patient outcomes, and facilitates clinical translation of different treatment modalities.

Intelligent Magnetic Microrobots with Fluorescent Internal Memory for Monitoring Intragastric Acidity

AbstractThis study investigates the dynamic fluctuations of pH caused by gastric acid secretion, a process of both biological and clinical significance, with microrobots. Abnormal patterns of acidity often indicate gastrointestinal diseases, underlying the importance of precise intragastric pH monitoring. Traditional methods using fluorescent probes face challenges due to their faint solid‐state fluorescence, limited target specificity, and accuracy. To overcome these obstacles, pH‐responsive fluorescent organic microparticles decorated with magnetite (Fe3O4) nanoparticles are engineered. These microrobots exhibit a unique fluorescence switching capability at a critical pH, enabling the monitoring of gastric acidity. The magnetic part of these microrobots ensures magnetic maneuverability to enable targeted navigation. The microrobots’ fluorescence switching mechanism is elucidated through comprehensive spectroscopy, microscopy, and X‐ray diffraction analyses, revealing molecular‐level structural transformations upon interaction with gastric acid and antacids. These transformations, specifically protonation and deprotonation of the microrobots’ fluorescent components, prompt a distinct fluorescence response correlating with pH shifts. In vitro and ex vivo experiments, simulating stomach conditions, confirm the microrobots’ efficacy in pH‐responsive imaging. The results showcase the promising diagnostic potential of microrobots for gastrointestinal tract diseases, marking a significant advancement in imaging‐based medical diagnostics at targeted locations.

Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment

In the nucleus, biological processes are driven by proteins that diffuse through and bind to a meshwork of nucleic acid polymers. To better understand this interplay, we present an imaging platform to simultaneously visualize single protein dynamics together with the local chromatin environment in live cells. Together with super-resolution imaging, new fluorescent probes, and biophysical modeling, we demonstrate that nucleosomes display differential diffusion and packing arrangements as chromatin density increases whereas the viscoelastic properties and accessibility of the interchromatin space remain constant. Perturbing nuclear functions impacts nucleosome diffusive properties in a manner that is dependent both on local chromatin density and on relative location within the nucleus. Our results support a model wherein transcription locally stabilizes nucleosomes while simultaneously allowing for the free exchange of nuclear proteins. Additionally, they reveal that nuclear heterogeneity arises from both active and passive processes and highlight the need to account for different organizational principles when modeling different chromatin environments.

A Novel Fluorescent Probe containing dihydropyrimidinone Analogue for Highly Sensitive, Selective Detection of Al(III) Ions with its Molecular Docking, ADME/T and Anticancer Impact

AbstractIn this investigation, a novel and promising chemosensor incorporating a dihydropyrimidinone moiety, namely; (E)‐4‐(4‐(dimethylamino)phenyl)‐5‐(3‐(4‐(dimethylamino)phenyl)acryloyl)‐6‐methyl‐3,4 dihydropyrimidin‐2(1H)‐one (DPDAD), has been successfully synthesized and characterized. The DPDAD chemosensor‘s response was evaluated in diverse solvents with varying polarities, shedding light on its solvatochromic behavior. The assessment of colorimetric and optical sensing attributes toward a range of metal ions such as Al(III), Cr(III), Mn II), Fe(III), Co(II), Ni(II), and Cu(II) was undertaken. Notably, DPDAD displayed discernible color alterations upon interaction with all the examined metal ions, with a significant bathochromic shift observed in the absorption spectra in the presence of Al(III), distinguishing it from the other metal ions. Furthermore, through detailed absorption and emission spectral analyses, DPDAD exhibited remarkable selectivity, sensitivity, and an on‐off‐on switchable behavior specifically with Al(III) ions, over the other metal ions. The binding constant was determined as 0.39×105 M−1, accompanied by a limit of detection (LOD) of 1.03×10−5 M. Notably, the DPDAD′s potential extends beyond metal ion sensing; it was computationally assessed for its capability to inhibit the γ‐secretase enzyme. Moreover, DPDAD′s antioxidant attributes were probed, and its inhibitory effect against a range of cancer cell lines was verified in‐vitro.

Pentacenequinone-Modulated 2D GdSn-PQ Nanosheets as a Fluorescent Probe for the Detection of Enrofloxacin in Biological and Environmental Samples.

The fate and effects of fluoroquinolone antibacterial (FQ) on the environment are important since there appears to be a surge in FQ resistance like enrofloxacin (ENR) in both environmental and clinical organisms. Numerous reports indicate that the sensing capabilities of these antibiotics need to be improved. Here, we have investigated the interaction of ENR with our synthesized pentacenequinone-modulated gadolinium-tin (GdSn-PQ) nanosheets and the formation of intermolecular interactions that caused the occurrence of aggregation-induced emission enhancement. The concept for designing hybrid metallic nanosheets comes from the unique features inherited from the parent organic precursor. Due to the distinct interaction between ENR and GdSn-PQ, the interstate conversion (ISC) between GdSn-PQ and ENR induces a significant wavelength shift in photoluminescence (PL), improving reliability, selectivity, and visibility compared to quenching- or AIEE-based methods without peak shifts, allowing for highly sensitive and visually detectable analyses. The fluorescence signal of GdSn-PQ exhibited a linear relationship (R2 = 0.9911), with the added ENR concentrations ranging from 5 to 90 nM, with a detection limit of 0.10 nM. We have demonstrated its potential and wide use in the detection of ENR in biological samples (human urine and blood serum) and environmental samples (tap water and seawater) with a recovery rate of 98- 108%. The current approach has demonstrated that the 2D GdSn-PQ nanosheet is a novel and powerful platform for future biological and environmental studies.

An Imidazo[1, 2-a]Pyridine Based Fluorescent Probe for the Continuous "on-off-on" Detection of Fe3+ and F.

An "on-off-on" fluorescent probe LK was synthesized from 2-benzoylpyridine and o-vanillin, which could sequentially detect Fe3+ and F- in DMSO/H2O solutions (v/v = 1/1, HEPES buffer, 1.0 mM, pH 7.0) with large Stokes shift (178nm). LK exhibited not only high selectivity and sensitivity towards Fe3+ and F-, but also strong anti-interference ability to other ions. LK was coordinated with Fe3+ at a ratio of 2:1, with a binding constant (Ka) of 1.3 × 104 M- 1. The detection limits for Fe3+ and F- were 6.9 × 10- 8 M and 3.0 × 10- 7 M, respectively. Due to its excellent sensing performance, LK was successfully applied in actual water samples and test papers for the detection of Fe3+ and F-.

High-Affinity NIR-Fluorescent Inhibitors for Tumor Imaging via Carbonic Anhydrase IX.

Tumor imaging and delivery of therapeutic agents may be achieved by designing high-affinity and high-selectivity compounds recognizing a tumor cell-expressing biomarker, such as carbonic anhydrase IX (CA IX). The CAIX, overexpressed in many hypoxic solid tumors, helps adjust to the energy requirements of the hypoxic environment, reduces intracellular acidification, and participates in the metastatic invasion of adjacent tissues. Here, we designed a series of sulfonamide compounds bearing CAIX-recognizing, high-affinity, and high-selectivity groups conjugated via a PEG linker to near-infrared (NIR) fluorescent probes used in the clinic for optically guided cancer surgery. We determined compound affinities for CAIX and other 11 catalytically active CA isozymes by the thermal shift assay and showed that the affinity Kd value of CAIX was in the subnanomolar range, hundred to thousand-fold higher than those of other CA isozymes. Similar affinities were also observed for CAIX expressed on the cancer cell surface in live HeLa cell cultures, as determined by the competition assay. The NIR-fluorescent compounds showed excellent properties in visualizing CAIX-positive tumors but not CAIX-negative knockout tumors in a nude mice xenograft model. These compounds would therefore be helpful in optically guided cancer surgery and could potentially be developed for anticancer treatment by radiotherapy.