Off-on Fluorescent Probe Research Articles

Metal-organic framework-based off-on fluorescent probe for highly selective and sensitive phosphate detection

The escalating demand for versatile and precise diagnostic tools across various biomedical applications has led to the development of an advanced assay utilizing a fluorescent metal-organic framework (MOF). Our novel approach centers on the synthesis of a controlled-explosive NH2-MIL-53(Fe) MOF, composed of trivalent iron ions and 2-aminoterephthalic acid. This framework possesses the unique capability to produce explosively enhanced fluorescence upon environmental triggers such as phosphate conditions, where it disintegrates to release intensely fluorescent molecules. The surface of NH2-MIL-53(Fe) MOF was further functionalized with poly(acrylic acid-co-maleic acid) polymers (PAAcoMA) to form PAAcoMA@MIL-53(Fe) MOF, thereby enhancing its stability. The presence of phosphate ions is detected by the degree of fluorescence resulting from the unquenching of PAAcoMA@MIL-53(Fe) MOF. This system demonstrates not only high sensitivity but also a broad dynamic range, making it suitable for phosphate ion detection. This innovative technology holds promise for significant advancements in the field of phosphate indicator-based biosensing, with potential applications in the development of PCR kits, thereby supporting a wide range of diagnostic and therapeutic applications.

A near-infrared fluorescent off-on probe with large Stokes shift for sensing hydrazine in vitro and in vivo

The development of effective approaches for detecting toxic hydrazine (N2H4) is of great importance for public health. In this work, a near-infrared (NIR) fluorescent probe (QLN-Hy) for trace hydrazine detection with a large Stokes shift was constructed. Hydrazine-activatable QLN-Hy displayed striking characteristics of high sensitivity (detection limit: 0.25 μM), high selectivity, as well as notable fluorescence enhancement at the NIR emission (692 nm) and large Stokes shift (104 nm). In particular, the color of QLN-Hy changed from purple to light blue, enabling the direct visualization of hydrazine in vapor and aqueous phases through the naked eye readily. Meanwhile, the practical feasibility of QLN-Hy was successfully evaluated by quantitatively detecting trace hydrazine in water samples (lake water, river water, rain water, tap water, drinking water) and mice samples (urine, serum). Importantly, probe QLN-Hy can be conveniently applied to monitor and visualizing hydrazine in cells and in vivo, clearly demonstrating its invaluable potential biological applications.

A novel "off-on" fluorescent probe for the detection of nickel ions and its clinical application.

Nickel serves as an essential micronutrient for the human body, playing a vital role in various enzymatic processes. However, excessive nickel entering the environment can cause pollution and pose serious risks to animals, plants, and human health. High concentrations of nickel ions in the human body increase the risk of various diseases, highlighting the need for accurate measurement of nickel ions levels. In this study, we designed a sequence-specific cleavage probe for nickel (II) ion called SSC-Ni. Similar to the TaqMan probe, SSC-Ni is an off-on fluorescent probe with an exceptionally low background fluorescence signal. It exhibits high detection specificity, making it highly selective for nickel ions, and the detection limit of the probe towards Ni2+ is as low as 82nM. The SSC-Ni probe can be utilized for convenient and cost-effective high-throughput quantitative detection of nickel ions in serum. Its user-friendly operation and affordability make it a practical solution. By addressing the lack of simple and effective nickel ion detection methods, this probe has the potential to contribute significantly to environmental monitoring and the protection of human health.

Biogenic Carbon Dot-Embedded Chitosan Hydrogels as a Two-Stage Fluorescence OFF–ON Probe for Sequential and Ratiometric Detection of Fe(III) and Glutathione

Biogenic Carbon Dot-Embedded Chitosan Hydrogels as a Two-Stage Fluorescence OFF–ON Probe for Sequential and Ratiometric Detection of Fe(III) and Glutathione

BODIPY Based OFF-ON Fluorescent Probe for Endogenous Carbon Monoxide Imaging in Living Cells.

Carbon monoxide (CO) is one of the signaling molecules that are ubiquitous in humans, which involves in the regulation of human physiology and pathology. In this work, the probe PEC was designed and synthesized based on BODIPY fluorophore that can selectively detect CO through reducing the nitro group to amino group, resulting in a "turn-on" fluorescence response with a simultaneous increase in the concentration of CO. The response is selective over a variety of relevant reactive free radicals, ions, and amino acid species. PEC has the advantages of good stability, good water solubility, and obvious changes in fluorescence signals. In addition, PEC can be used to detect and track endogenous CO in living cells.

Rapid and sensitive detection of endogenous HClO in living cells and zebrafish using a phenothiazine-based fluorescent probe

Hypochlorous acid (HClO) is a reactive oxygen species (ROS) that plays a critical role in numerous pathological and physiological processes. Abnormal concentrations of HClO in vivo have been closely linked to many diseases, including inflammatory disorders and cancer. In this work, an on-off fluorescent probe PTZ based on phenothiazine was synthesized for specific detection of HClO. PTZ demonstrated excellent selectivity, biocompatibility, rapid response, pH stability, and low limits of detection (5.2 nM). Furthermore, PTZ can detect both exogenous and endogenous HClO rapidly in living cells and zebrafish, which provides it with broad potential applications in life sciences.

The g-C3N4/BSA@MnO2 nanocomposites fluorescent off-on probe for detection and imaging of ascorbic acid in living cells

g-C3N4/BSA@MnO2 fluorescent off-on probe was constructed for sensitive and selective detection of ascorbic acid (AA). BSA@MnO2 nanoparticles using bovine serum albumin (BSA) as a template were anchored on the surface of graphite-phase carbon nitride nanosheets (g-C3N4 NSs) via electrostatic attraction to synthesize the g-C3N4/BSA@MnO2 nanocomposites. The fluorescence of g-C3N4 NSs was quenched by BSA@MnO2 nanoparticles (NPs) via fluorescence resonance energy transfer (FRET) and recovered in the presence of AA via the redox reaction between AA and MnO2. The nanocomposites therefore realized the fluorescent off–on detection of AA. Asatisfactory linear range of 0–120 μM and a limit of detection of 133 nM were obtained. The nanoprobe was applied for the detection of AA in food and drug samples as well as the fluorescent images of exogenous AA in Raw cells. The results showed that the nanoprobe possessed excellent properties for AA detection and broadened the biochemical analysis applications of g-C3N4-based nanomaterials.

RETRACTED: An acridone-derived fluorescent off-on probe for detection and in vivo imaging of nitroreductase

Understanding the functions of enzymes in various physiological processes is important, but the design of signaling probes for fast analysis of enzymatic activity is particularly challenging. Herein, a fluorescence-enhanced probe, 10-methyl-2-nitro-acridone (MNA), was synthesized and applied to analyze nitroreductase (NTR) activity in vitro and in vivo. The detection mechanism is based on the nitro group in MNA reacting toward NTR with high reactivity and generating 10-methyl-2-amino- acridone (MAA) accompanied by an obvious fluorescence signal enhancement at 525 nm emission. The probe shows low cytotoxicity, fast response, and high selectivity and sensitivity with a limit of detection as low as 150 ng·mL−1. The probe was also employed for two-photon fluorescence imaging of NTR in zebrafish in vivo revealing the distribution of NTR. Versus existing NTR probes, the proposed probe shows favorable analytical performance including near-infrared light excitation with no other byproducts produced after the reaction. The superior properties of this signaling probe allow it to become a fluorescence imaging candidate in other biosystems.

In situ microwave-assisted preparation of NS-codoped carbon dots stabilized silver nanoparticles as an off-on fluorescent probe for trace Hg2+ detection

An off-on fluorescent probe (NS-CDs-AgNPs) was synthesized based on a one-pot microwave process by utilizing N, S co-doping carbon dots (NS-CDs) and silver nitrate as precursors. The significant peak of NS-CDs-AgNPs at 393 nm in ultraviolet spectrum indicated silver nanoparticle (AgNPs) were successfully synthesized. A faint blue fluorescence emission (442 nm) was displayed when excited NS-CDs-AgNPs at 371 nm. A remarkable fluorescence recovery was observed upon adding of trance Hg2+, whereas the other heavy metal ions did not elicit this response. The reason for this phenomenon was revealed in this work that a spontaneous redox reaction occurred between NS-CDs-AgNPs and Hg2+, which leaded to the formation of NS-CDs-Agn-2NPsHg complexes. On the basis of this mechanism, a new off-on fluorescent analytical method was constructed for Hg2+ detection with linear range of 10–400 nM (R2 = 0.9941), and the detection limit (LOD) of 5.16 nM. Additionally, satisfactory recovery (90.28%–106.13%) and the relative standard deviation (RSD) (RSD＜5.21%) were obtained in water sample detection. More importantly, the NS-CDs-AgNPs exhibited lower cytotoxicity and better biocompatibility, indicating a huge potential in cell imaging and clinical medicine.

GSH-specific fluorescent probe for sensing, bioimaging, rapid screening of natural inhibitor Celastrol and ccRCC theranostics.

High level of intracellular glutathione (GSH) has been identified as a major barrier for cancer therapy. Therefore, effective regulation of GSH can be regarded as a novel approach for cancer therapy. In this study, an off-on fluorescent probe (NBD-P) is developed for selective and sensitive sensing GSH. NBD-P has a good cell membrane permeability that can be applied in bioimaging endogenous GSH in living cells. Moreover, the NBD-P probe is used to visualize GSH in animal models. In addition, a rapid drug screening method is successfully established using the fluorescent probe NBD-P. A potent natural inhibitor of GSH is identified as Celastrol from Tripterygium wilfordii Hook F, which effectively triggers mitochondrial apoptosis in clear cell renal cell carcinoma (ccRCC). More importantly, NBD-P can selectively respond to GSH fluctuations to distinguish cancer tissues from normal tissues. Thus, the present study provides insights into fluorescence probes for the screening GSH inhibitors and cancer diagnosis, as well as in-depth exploration of the anti-cancer effects of Traditional Chinese Medicine (TCM).

An Off-Off fluorescence sensor based on ZnS quantum dots for detection of glutathione

Quantum dots (QDs) are excellent fluorescent indicators for chemical and biological analysis. In this paper, an Off-Off fluorescence sensor based on ZnS quantum dots was designed. It was found that Co2+ can quench the fluorescence of ZnS QDs, moreover glutathione (GSH) can further quench the fluorescence. Therefore, this method can be used for indirect detection of GSH. However, if change Co2+ into other metal ions, the system cannot be used to detect GSH indirectly. For direct detection GSH, that is adding GSH without Co2+, the fluorescence intensity changes little, while only amino acid or monosaccharide has no effect. When indirect detection of GSH based on this Off-Off fluorescent probe, the fluorescence quenching was linearly related to the concentration range of 1–300 μM GSH, and the detection limit could reach 0.48 μM, which can rival most Off-On and On-Off fluorescent probe. The relative standard deviation for parallel measurement of 300 μmol·L-1 GSH solution (for n = 10) was 1.43 %.

Facile preparation of N, S co-doped carbon dots and their application to a novel off-on fluorescent probe for selective determination of Hg2+

In this work, citric acid (CA) and glutathione (GSH) were selected as the raw materials for preparation carbon dote co-doped with N and S (NS-CDs) via microwave heating method. The obtained NS-CDs displayed stable and strong blue luminescence with a maximum emission (λem) wavelength of 442 nm and a maximum excitation (λex) wavelength of 371 nm, and their fluorescence quantum yield (FLQY) was 10.9%. The fluorescence of NS-CDs was quenched by silver nanoparticles (AgNPs) through a combination of static quenching effect and inner filter effect (IFE), and could be recovered by Hg2+ even at nanomolar levels ascribing to redox reaction between Hg2+ and AgNPs. Based upon this phenomenon, a novel off-on fluorescent probe (NS-CDs - AgNPs) for determination trace Hg2+ in aqueous solution was constructed using the obtained NS-CDs and AgNPs. Under optimal conditions, NS-CDs - AgNPs exhibited a wide linearity range of 10–90 nM (R2 = 0.993) for Hg2+and a low LOD of 4.2 nM. NS-CDs - AgNPs was successfully utilized for monitoring Hg2+ in real water samples with the recoveries of 91.4–108.6% (RSD <5.84%), which indicated that the fluorescent probe has enormous application potential to detect trace Hg2+ in real water samples.

Biomimetic macrophage membrane-coated gold-quantum dots with tumor microenvironment stimuli-responsive capability for tumor theranostic.

Tumor microenvironment (TME) is intently related to tumor growth, progression and invasion, leading to drug resistance and insufficient therapeutic efficacy. However, remodeling TME and utilizing TME for exploring intelligent nanomaterials that can realize tumor theranostic is still challenging. Nowadays, the theranostic based on chemotherapy exposes some deficiencies, such as low targeting, weak permeability and premature clearance. Furthermore, it is challenging to cure drug-resistant tumors effectively. For the sake of solving these problems, a biomimetic decomposable nano-theranostic (MMV-Au-CDs-DOX) was well-established in this work. The Au-CDs are coated with macrophage-derived microvesicle to realize drug release accurately and enhance the biocompatibility of internal nanoparticles. Furthermore, MMV-Au-CDs-DOX would locate in the inflammation position of tumor, and disintegrate correspondingly into pieces with certain different functions stimulated by TME. Subsequently, the released anti-tumor nanodrugs were used for multimodal therapy, including chemotherapy and hemodynamic therapy. In addition, combined with the ability of Au-CDs to recognize GSH specifically, the off-on fluorescent probe was constructed to monitor the GSH of tumor cells and provided information on chemotherapy resistance.

An acid-enhanced OFF-ON fluorescent probe for the detection of hypochlorous acid in rheumatoid arthritis

Excessive production of hypochlorite acid (HClO) and lactic acid are general hallmarks in the microenvironment of rheumatoid arthritis (RA). Here, we, for the first time, report an acid-enhanced “OFF-ON” fluorescent probe PPS for the detection of HClO in vivo. The probe PPS showed good water solubility, large Stokes shift (143 nm), and fast response toward HClO within 100 s. In the presence of HClO, the sulfur atom in the core of phenothiazine would be oxidized into sulfoxide, triggering intense fluorescence at 580 nm, whose fluorescence intensity could be further enhanced under acidic conditions. Moreover, the exogenous and endogenous HClO in living cells could be sensitively and selectively detected by PPS with a low LOD of 24 nM. Notably, PPS was able to rapidly visualize endogenous HClO generation in a RA mouse model, exhibiting a 2.3-fold higher fluorescence intensity than it in normal joint and 4.1-fold enhanced fluorescence intensity at acidic pH.

Rapid microwave synthesis of N,S-doped carbon quantum dots as a novel turn off-on sensor for label-free determination of copper and etidronate disodium

An environmentally-friendly, selective and rapid turn off-on fluorescent probe for both copper (Cu2+) and etidronate disodium (ETD) detection was derived from nitrogen/sulfur co-doping of carbon dot (N,S-CD). The N,S-CDs were produced, for first time, through microwave-assisted pyrolysis in only 60 s using readily accessible and cheap precursors (citric acid and thiosemicarbazide). The proposed synthesis method resulted in N,S-CDs with narrow particle size distribution, high product yield (64.38 wt%) and high doping efficiency (N, 28.56% and S, 8.47%). The turn off-on sensor was developed after demonstrating the ability of Cu2+ to quench fluorescence of the produced CDs and probable fluorescence restoration through complexation of Cu2+ by the bisphosphonate group of ETD. The developed sensor showed a good performance for Cu2+ and ETD detection with a linear range of 5–125 μM and 30–210 μM, respectively. This developed platform could be applied for routine analysis of Cu2+ and ETD with good recoveries.

A curcumin-based AIEE-active fluorescent probe for Cu2+ detection in aqueous solution.

Curcuminoids have been extensively investigated as metal ion probes, but the intrinsic aggregation-caused-quenching (ACQ) characteristic of curcumin would hinder their applications in aqueous solution. Fortunately, tetraphenylethylene (TPE) could endow the compounds with aggregation-induced emission (AIE)/aggregation-induced enhanced emission (AIEE) characteristics to eliminate the ACQ effect. According to this strategy, a series of TPE-modified curcumin derivatives L1–4 were prepared and studied for their AIEE properties. Among the four TPE-curcumin analogues, only L1 particles have been successfully used as an on-off fluorescence probe for detecting Cu2+ in aqueous solution. The fluorescence titration experiment determined its detection limit of 1.49 × 10−7 mol L−1, and the binding ratio between L1 and Cu2+ was estimated as 2 : 1, which was in agreement with the results of high resolution mass spectrum and Job's plot. In addition, the binding constant was evaluated as 6.77 × 102 M−1 using a Benesi–Hildebrand plot. Finally, the obtained L1-based indicator paper showed significant fluorescence response to Cu2+ aqueous solution. This TPE-modified strategy improves the detection capability of curcumin probe in aqueous solution and provides a feasible way to obtain other probes with ACQ characteristics.

A novel near-infrared fluorescence off-on probe for imaging hypoxia and nitroreductase in cells and in vivo

Nitroreductase (NTR) is a highly expressed endogenous enzyme in hypoxic tumor cells, which is associated with the hypoxic degree in tumors. Therefore, it is particularly important to develop low-toxicity and high-sensitivity fluorescent probes for NTR. Herein, we report an NTR-activated near-infrared probe with good selectivity and sensitivity. More importantly, the background fluorescence signal is effectively reduced due to the quenching effect of nitro group as well as the spironolactone (ring-closed) form of rhodamine moiety. Upon reaction with NTR, the probe exhibits a remarkable fluorescence off-on response at 740 nm (about 32-fold intensity enhancement), with an extremely low detection limit of 1.09 ng/mL. Moreover, the probe is able to target mitochondria. With this probe, we have achieved the visualization of NTR overexpression in hypoxic cancer cells, as well as in hypoxic tumors in vivo as revealed in the tumor-bearing mouse model. By using this probe, some essential information may be revealed about hypoxia-relevant diseases.

A Fast-Responsive OFF-ON Near-Infrared-II Fluorescent Probe for In Vivo Detection of Hypochlorous Acid in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease, and its etiology is closely related to the overproduction of hypochlorous acid (HClO). However, early detection of RA using an activatable near-infrared-II (NIR-II, 1000-1700 nm) fluorescent probe remains challenging. Herein, we first report an "OFF-ON" NIR-II fluorescent probe named PTA (phenothiazine triphenylamine) for imaging HClO in deep-seated early RA. Electron-rich phenothiazine in the core of PTA was utilized as both an HClO-recognition moiety and a precursor of electron acceptors, displaying a typical donor-acceptor-donor structure with excellent NIR-II emission at 936/1237 nm once reacted with HClO. The probe PTA exhibited good water solubility, high photostability, and rapid response capability toward HClO within 30 s. Moreover, it was able to sensitively and specifically detect exogenous and endogenous HClO in living cells in both visible and NIR-II windows. Notably, PTA enabled the sensitive and rapid visualization of HClO generation in an inflammatory RA mouse model, showing a 4.3-fold higher NIR-II fluorescence intensity than that in normal hindlimb joints. These results demonstrate that PTA holds great promise as a robust platform for diagnosis of HOCl-mediated inflammatory disorders.

An off-on fluorescent probe based on graphene quantum dots intercalated hydrotalcite for determination of ascorbic acid and phytase

A new off-on fluorescent probe was successfully synthesized and used to detect ascorbic acid and phytase. The composite material of hydrotalcite and graphene quantum dots were synthesized through citrate intercalated hydrotalcite using hydrothermal carbonization method. The layered structure of hydrotalcite can prevent the aggregation and promote the uniformity of graphene quantum dots. The off-on fluorescent probe detection mechanism is as follows. Fe3+ ions were firstly added into the solution of the composite material, and the fluorescence was quenched. Then, ascorbic acid was added into the fluorescence probe system, which reduced iron ions and turned on fluorescence to realize the detection of ascorbic acid. In addition, the reaction of phytase and l-ascorbyl-2-phosphate can produce ascorbic acid, further achieving the purpose of phytase detection. The concentration of the analyte and the recovery of the fluorescence intensity show a linear relationship, the linear ranges were 5−300 μmol L−1 and 0.1–4 U mL−1 for ascorbic acid and phytase, respectively. The recoveries of the experiment were 96.3 %–103.1 % and 95.4 %–104.9 %, respectively. The fluorescence method has the advantages of fast, stable, high sensitivity and high selectivity, which has been successfully applied to the determination of ascorbic acid in fruit juice and phytase in feed.

Superoxide anion turns on the fluorescence of carbon dots-ferric complex for sensing

Superoxide anion (O2•−) is one of the most important reactive oxygen species and its sensitive detection is of great significance and challenging in the field of environmental and hazardous chemicals monitoring. Herein, we report an off-on fluorescent probe based on ferric functionalized carbon dots (CDs) which were synthesized using p-phenylenediamine as starting material for the detection of O2•−. The initial green fluorescence of CDs was greatly quenched by Fe3+ based on energy transfer effect on account of the selective formation of ferric complex on the surface of CDs, but not by other metal ions. Interestingly, the fluorescence of CDs could be readily and selectively recovered upon the addition of O2•−, which can be used for the senstivie detection of superoxide. This type of off-on probe exhibited good photostability and high selectivity toward O2•− among other interfering substances including metal ions, reactive oxygen species as well as reductant substances. The probe showed good linearity with the concentration of O2•−, and the limit of detection for O2•− was estimated down to 25 pM in aqueous solution. Moreover, a paper based sensor for O2•− was fabricated with a visual detection limit as low as 4.4 nM, demonstrating a promising application for practical detection of superoxide anion.