A "turn-on" fluorescence sensor for hydroquinone detection based on BSA doped carbon dots (BSA@CDs) from crawfish shells.

By using crawfish shells as the precursor and hydrothermal synthesis, Bovine serum albumin doped carbon dots (BSA@CDs) were prepared without excessive chemical reagents. The relationship between the fluorescence properties of different BSA@CDs and BSA amount was investigated by variouscharacterization techniques. When the amount of BSA added was 30 %, the prepared BSA@CDs' quantum yield (QY) reached 25.01 %, which was the highest. Inner Filter Effect (IFE) suggested that Cr (VI) can selectively quench the fluorescence of BSA@CDs. Cr (VI) can be reduced to Cr (III) by Hydroquinone (HQ), thus recovering the fluorescence. Accordingly, using BSA@CDs as a probe, a "turn-on" fluorescence sensor applied in HQ determination was constructed. The linear range was 10-200 µmol/L and limit of detection (LOD) was 0.18 µmol/L. Further, it has been employed to the determination of HQ in both crawfish tail meat and aquaculture water with good performance.

Esterase-Responsive Fluorogenic Prodrugs of Aldose Reductase Inhibitor Epalrestat: An Innovative Strategy toward Enhanced Anticancer Activity.

In addition to the conventional chemotherapeutic drugs, potent inhibitors of key enzymes that are differentially overexpressed in cancer cells and associated with its progression are often considered as the drugs of choice for treating cancer. Aldose reductase (AR), which is primarily associated with complications of diabetes, is known to be closely related to the development of cancer and drug resistance. Epalrestat (EPA), an FDA-approved drug, is a potent inhibitor of AR and exhibits anticancer activity. However, its poor pharmacokinetic properties limit its bioavailability and therapeutic benefits. We report herein the first examples of esterase-responsive turn-on fluorogenic prodrugs for the sustained release of EPA to cancer cells with a turn-on fluorescence readout. Carboxylesterases are known to be overexpressed in several organ-specific cancer cells and help in selective uncaging of drug from the prodrugs. The prodrugs were synthesized using a multistep organic synthesis and successfully characterized. Absorption and emission spectroscopic studies indicated successful activation of the prodrugs in the presence of porcine liver esterase (PLE) under physiological condition. HPLC studies revealed a simultaneous release of both the drug and the fluorophore from the prodrugs over time with mechanistic insights. While the inhibitory potential of EPA released from the prodrugs toward the enzyme AR was validated in the aqueous medium, the anticancer activity of the prodrugs was studied in a representative cervical cancer cell line. Interestingly, our results revealed that the development of the prodrugs can significantly enhance the anticancer potential of EPA. Finally, the drug uncaging process from the prodrugs by the intracellular esterases was studied in the cellular medium by measuring the turn-on fluorescence using fluorescence microscopy. Therefore, the present study highlights the rational development of the fluorogenic prodrugs of EPA, which will help enhance its anticancer potential with better therapeutic potential.

Recent Developments On Activatable Turn-On Fluorogenic Donors of Hydrogen Sulfide (H2S).

Hydrogen sulfide (H2S) is considered the third member of the gasotransmitter family, along with nitric oxide (NO) and carbon monoxide (CO). Besides its role in physiological and pathophysiological conditions, the promising therapeutic potential of this small-molecule makes it advantageous for various pharmaceutical applications. The endogenous production of H2S at a lower concentration is crucial in maintaining redox balance and cellular homeostasis, and the dysregulation leads to various disease states. In the event of H2S deficiency, the exogenous donation of H2S could help maintain the optimal cellular concentration of H2S and cellular homeostasis. Over the last several years, researchers have developed numerous small-molecule non-fluorogenic organosulfur compounds as H2S donors and investigated their pharmacological potentials. However, reports on stimuli-responsive turn-on fluorogenic donors of H2S have appeared recently. Interestingly, the fluorogenic H2S donors offer additional advantages with the non-invasive real-time monitoring of the H2S release utilizing the simultaneous turn-on fluorogenic processes. The review summarizes the recent developments in turn-on fluorogenic donors of H2S and the potential biological applications that have developed over the years.

Fluorimetric Detection of Insulin Misfolding by Probes Derived from Functionalized Fluorene Frameworks.

A group of functionalized fluorene derivatives that are structurally similar to the cellular prion protein ligand N,N'-(methylenedi-4,1-phenylene)bis [2-(1-pyrrolidinyl)acetamide] (GN8) have been synthesized. These compounds show remarkable native fluorescence due to the fluorene ring. The substituents introduced at positions 2 and 7 of the fluorene moiety are sufficiently flexible to accommodate the beta-conformational folding that develops in amyloidogenic proteins. Changes in the native fluorescence of these fluorene derivatives provide evidence of transformations in the amyloidogenic aggregation processes of insulin. The increase observed in the fluorescence intensity of the sensors in the presence of native insulin or amyloid aggregates suggest their potential use as fluorescence probes for detecting abnormal conformations; therefore, the compounds can be proposed for use as "turn-on" fluorescence sensors. Protein-sensor dissociation constants are in the 5-10 µM range and an intermolecular charge transfer process between the protein and the sensors can be successfully exploited for the sensitive detection of abnormal insulin conformations. The values obtained for the Stern-Volmer quenching constant for compound 4 as a consequence of the sensor-protein interaction are comparable to those obtained for the reference compound GN8. Fluorene derivatives showed good performance in scavenging reactive oxygen species (ROS), and they show antioxidant capacity according to the FRAP and DPPH assays.

Differential detection of H1N1 virus spiker proteins by two hexaphenylbutadiene isomers based on size-matching principle.

As one of the high pathogenic influenza viruses, H1N1 virus easily induces to serious diseases, even leading to death. To date, all detection methods for H1N1 virus had shortcomings, including high equipment cost, time consumption, and etc. Therefore, a novel detection method should be established to achieve more convenient, rapid, and low-cost detection. In this work, an isomer of HPBmN-I with aggregation-induced emission characteristic was firstly synthesized on the basis of our previous reported HPBpN-I. The results showed that HPBmN-I only selectively binds to N1 in the presence of H1, while HPBpN-I can exhibit total fluorescence response to H1 and N1 in H1/N1 mixture. The limited of detection (LOD) of HPBmN-I to N1 was estimated to be 20.82 ng/mL in normal saline (NS) according to the IUPAC-based approach. The simulation calculations based on molecular docking revealed that four HPBmN-I molecules combine well with the hydrophobic cavity of N1 and achieve the fluorescence enhancement due to size matching with each other. The combination of HPBpN-I and HPBmN-I as probes was successfully used to quantitatively detect H1 and N1 in real H1N1 virus. Compared to enzyme-linked immunosorbent assay (ELISA) method, the established method not only showed the same detection accuracy but also had the advantages of real-time, ease of preparation, and low-cost, demonstrating potential market prospects.

A carbon dots-MnO2 nanosheet-based turn-on pseudochemodosimeter as low-cost probe for selective detection of hazardous mercury ion contaminations in water.

Mercury is a highly hazardous element due to its profound toxicity and wide abundance in the environment. Despite the availability of various fluorimetric detection tools for Hg2+, including organic fluorophores and aptasensors, they often suffer from shortcomings like the utilization of expensive chemicals and toxic organic solvents, multi-step synthesis, sometimes with poor selectivity and low sensitivity. Whereas, biomass-derived fluorophores, such as carbon dots (CDs), present themselves as cost-effective and environmentally benign alternatives that exhibit comparable efficacy. Herein, we report a reaction-driven sensing assembly based on CDs, MnO2 nanosheets, and hydroquinone monothiocarbonate (HQTC) for the detection of Hg2+ ions, which relies on the formation of a CDs-MnO2 FRET-conjugate, resulting in the quenching of the intrinsic fluorescence of CDs. In a pseudochemodosimetric approach, the thiophilic nature of mercury was utilized for in-situ generation of the reducing species, hydroquinone from HQTC, resulting in the reduction of MnO2 nanosheets, the release of fluorescent CDs back to the solution. The low limit of detection (LOD) was achieved as 2 ppb (0.01 µM). The probe worked efficiently in real water samples like sea, river with good recovery of spiked Hg2+ and in some Indian ayurvedic medicines as well. Furthermore, solid-phase detection with sodium alginate beads demonstrated the ability of this cost-effective sensing assembly for onsite detection of Hg2+ ions.

Novel & Smart Sensing of Acetate and Hypochlorite Ions With Relay Recognition of Cr3+ Ion With Fluorescence Turn-on: Application in Bio-imaging & Real Sample Analysis.

The receptor-bearing anthraquinone chromophore was synthesized by a simple aldamine condensation reaction, and its anion sensing properties were investigated via colorimetric, UV-vis, photoluminescence, and DFT calculations. The synthesized receptor detects both acetate and hypochlorite ions, where remarkable colorimetric transitions were observed from pink to purple for the acetate ion and pink to blue for the hypochlorite ion. Moreover, in the occurrence of the acetate ion, it shows an admirable answer for the Cr3+ ion, which changes its purple color to pink, while no notable change was observed for other ions. The detection limits of receptors with acetate and hypochlorite are 7.1 × 10-7 M and 9.4 × 10-7 M, respectively. The DFT calculation was performed to better understand the sensing mechanisms of both AcO- and ClO- ions. Furthermore, receptors were effectively utilized in the preparation of optical sensors supported by silica gel for the detection of AcO- and ClO- ions. The receptor proved itself to be potentially useful for real-life application by sensing AcO - in vinegar and ClO - ions in ala. Furthermore, its preeminent detection properties enabled the successful labeling of the AcO- ion in living biological cells.

Turn-on Rhodamine Glycoconjugates Enable Real-Time GLUT Activity Monitoring in Live Cells and In Vivo.

The direct relationship between facilitative glucose transporters (GLUTs) and metabolic diseases opens new avenues for sensing metabolic deregulations and drives the development of molecular probes for GLUT-targeted detection of metabolic diseases. Radiotracer-based molecular imaging probes have been effectively utilized in reporting alterations in sugar uptake as an indication of metabolic deregulations, cancer development, or inflammation. Progress in developing fluorophore-based tools facilitated GLUT-specific analyses using more accessible fluorescence-based instrumentation. However, restrictions on the emission range of fluorophores and the requirement for substantial post-treatments to reduce background fluorescence have brought to light the critical directions for improvement of the technology for broader use in screening applications. Here we present turn-on GLUT activity reporters activated upon cells' internalization. We demonstrate a specific delivery of a sizable rhodamine B fluorophore through GLUT5 and showcase a stringent requirement in conjugate structure for maintaining a GLUT-specific uptake. With the turn-on GLUT probes, we demonstrate the feasibility of high-throughput fluorescence microscopy and flow cytometry-based GLUT activity screening in live cells and the probes' applicability for assessing sugar uptake alterations in vivo.

Anthraquinone Based Sensors for the Selective Detection of Cyanide Ion with Turn on Fluorescence with Logic Gate & Real Sample Applications.

In recent years, there is an increasing interest in finding better and more efficient ways to detect CN- ions. Most of the anthraquinone-based probes show less fluorescence This paper presents the design and synthesis of a new anthraquinone based imine probe with good colorimetric sensing property and fluorescent turn on behavior toward CN- ion. Herein, we report a receptor with both colorimetric and fluorescent enhancement of cyanide ion in DMSO medium is synthesized. The synthesized receptor shows an immediate color change from orange to pink when cyanide is added; and it can be readily observed visually due to the presence of diverse p-conjugated systems in the receptor. These studies were confirmed by UV-Visible, PL studies, DFT, HRMS and 1H NMR titration. Moreover, this receptor shows 1:1 stoichiometry and micromolar detection limit. Further the receptor was applied to a real sample in finger millet (Eleusine Coracana) to detect the presence of cyanide ion. Moreover, the receptor is applicable toward INHIBITION, IMPLICATION logic gates with two input systems.

A Simple Live Cell Imaging "Turn-On" Fluorescence Probe for the Selective and Sensitive Detection of Aqueous Hg2+ Ions.

A simple, efficient, and reversible fluorescent sensor probe, PBA (2,6-dimethyl pyrone barbituric acid conjugate), comprised of a pro-aromatic donor conjugated with a barbituric acid, was developed for the detection of highly toxic mercuric ions. The probe showed high selectivity and "Turn-On" fluorescence response towards Hg2+ among various metal cations such as Na+, Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Ba2+, Hg2+, and Pb2+, in both homogeneous and microheterogeneous micelle medium sodium dodecyl sulphate (SDS). The binding stoichiometry, limit of detection (LOD), and binding constant for the PBA-Hg complex were determined. The mechanism of binding was ascertained using the N,N'-dimethylbarbituric acid conjugate of 2,6-dimethylpyran (PDMBA), where no binding interaction by deprotonation is possible. In the presence of cysteamine hydrochloride and trifluoroacetic acid (TFA), the complexation of Hg2+ with PBA was demonstrated to be reversible, indicating its potential for the development of reusable sensors. Moreover, the practical applicability of PBA in monitoring Hg2+ in living cells was also evaluated.

A highly sensitive hemicyanine-based near-infrared fluorescence sensor for detecting toxic amyloid aggregates in human serum.

The development of an accurate and sensitive sensor for detecting amyloid plaques, which are responsible for many protein disorders like Alzheimer's disease, is crucial for early diagnosis. Recently, there has been a notable increase in the development of fluorescence probes that exhibit emission in the red region (>600 nm), aiming to effectively tackle the challenges encountered when working with complex biological matrices. In the current investigation, a hemicyanine-based probe, called LDS730, has been used for the sensing of amyloid fibrils, which belong to the Near-Infrared Fluorescence (NIRF) family of dyes. NIRF probes provide higher precision in detection, prevent photo-damage, and minimize the autofluorescence of biological specimens. The LDS730 sensor emits in the near-infrared region and shows a 110-fold increase in fluorescence turn-on emission when bound to insulin fibrils, making it a highly sensitive sensor. The sensor has an emission maximum of ~710 nm in a fibril-bound state, which shows a significant red shift along with a Stokes' shift of ~50 nm. The LDS730 sensor also displays excellent performance in the complicated human serum matrix, with a limit of detection (LOD) of 103 nM. Molecular docking calculations suggest that the most likely binding location of LDS730 in the fibrillar structure is the inner channels of amyloid fibrils along its long axis, and the sensor engages in several types of hydrophobic interactions with neighboring amino acid residues of the fibrillar structure. Overall, this new amyloid sensor has great potential for the early detection of amyloid plaques and for improving diagnostic accuracy.

Improving anion sensing ability of the indolocarbazole-based fluorescence turn-on sensor by increasing salicylaldehyde response unit.

Detection abilities on tested subjects of sensors should be closely connected to the sensing unit numbers. Herein, two anion sensors ICZ-o-1S and ICZ-o-2S were synthesized by using indolo (2,3-a) carbazoles as fluorescent chromophore and salicylaldehyde as recognition site. Though UV-Vis and fluorescent ways, it demonstrated that F- can induce the sensor solutions becoming colored from colorless to yellow green, and can endow them with bright green turn-on fluorescence, proving their sensitive and selective sensing on F-. Accordingly, the F ion sensing studies including anti-interference abilities against to other anions on fluorescence response, stoichiometric ratios of sensor-F- in 1 : 1 and 1 : 2, -OH deprotonation sensing mechanism confirmed by 1H NMR titration and theoretical calculation were fully covered. Most importantly, fluoride ion detection limits achieved by ICZ-o-1S and ICZ-o-2S were 1.8 × 10-7 M and 6.0 × 10-8 M, respectively, the latter with two sensing units exhibited 3 times lower detection limit outcompeted to the former with only one sensing unit, rendering the sensor design strategy of improving detecting ability by increasing sensing unit number was rational. The practical application of F- detection in water-containing environment calibrated from the standard curve between the fluorescence intensity of sensor-F- system and the changing F- concentration was conducted. In addition, the accuracy of the sensor on detecting F- was evaluated by the spiked recovery experiment, therefore, the fast and convenient F- concentration detection based on the fluorescence color RGB values of the tested sensor-sample mixture was investigated. Consequently, the results obtained by these two sensors should deliver effective supports on designing high-performance sensors featuring naked-eye and fluorescence turn-on anion sensing by altering the response unit numbers.

A hypochlorite-activated strategy for realizing fluorescence turn-on, type I and type II ROS-combined photodynamic tumor ablation.

The combination of cancer cell-activated fluorescence and the advantages of both type I and type II photodynamic therapy (PDT) capabilities to achieve a synergistic therapeutic effect in a complex tumor environment is highly desirable. Herein, we report an approach by means of tumor intracellular hypochlorite (ClO-) to turn on fluorescence integrated with type I and II ROS generation for imaging-guided PDT. The resultant PTZSPy functions as a type II photosensitizer with mitochondria-targeting capability. In the presence of ClO-, PTZSPy is transformed into its oxidized counterpart SPTZSPy, turns on an orange-red fluorescence and triggers the type I ROS generation ability. Biological studies revealed that PTZSPy can accurately distinguishes tumor cells from normal cells, dynamically monitors the cell ablation process and be utilized for theranostics in MCF-7 tumor-bearing nude mice in vivo. This work provides an innovative strategy exploiting the highly abundant ClO- in tumor cells for the type I and II ROS two-pronged and imaging-guided PDT.

Highly selective chemosensor for the sensitive detection of Hg2+ in aqueous media and its cell imaging application.

The deleterious toxicity of Hg2+ on ecological and biological system makes it crucial for the precise monitoring of Hg2+. Herein, we prepared a novel "turn-on" chemosensor N'-(4-(methylthio)butan-2-ylidene) rhodamine B hydrazide (denoted as MTRH) by a simple two-step reaction. MTRH exhibited an ultra-low detection limit (LOD) in fluorescence measurement of Hg2+ in pure aqueous media, which was estimated to be 1.3 × 10-9 mol·L-1. Moreover, the proposed chemosensor holds the ability of visualizing Hg2+ by the distinct color change of the solution. The corresponding recognition mechanism was investigated by Job's plots, mass spectrometry and DFT calculation analysis. Importantly, the characteristics such as high sensitivity, low cytotoxicity and good biocompatibility of MTRH exhibited in the application of detecting Hg2+ in real water sample and bioimaging of intracellular Hg2+ prove that MTRH is a promising tool to evaluate the levels of Hg2+ in complex biological systems.

Coordination polymer nanoprobe integrated carbon dot and phenol red for turn-on fluorescence detection of urease activity.

The potential of coordination polymers (CPs) as a host of integrating multiple guest species to construct a fluorescence resonance energy transfer (FRET) nanoprobe was demonstrated. The ZnCPs built from zinc(II) and adenine was employed as a model of CPs to integrate carbon dot (CD) and phenol red (PR) for producing the FRET nanoprobe (CD/PR@ZnCPs). Benefiting from the confinement effect of ZnCPs, the integrated CD and PR can be brought in close proximity to favor the occurrence of FRET process from CD to PR, which leads to the quenching of CD fluorescence. However, the FRET process was disrupted upon the red-shift of PR absorption from 428 to 562 nm in alkaline medium, and consequently switches on the fluorescence of CD/PR@ZnCPs. Based on this finding, by utilizing urease to hydrolyze urea and mediate medium pH, a turn-on fluorescent method was established for the detection of urease activity. This fluorescent method has a linear response that covers 5 to 150 U/L urease with a detection limit of 0.74 U/L and exhibits an excellent selectivity over other enzymes. The successful determination of urease in saliva samples demonstrates the applicability of the fluorescent nanoprobe in complex biological matrix.

Turn-on fluorescence probing of amyloid fibrils by the proto-berberine alkaloids and the study of their interactions.

The aggregation of amyloid proteins is highly related to the occurrence and development of neurodegenerative and metabolic diseases. The detection of amyloid fibrils or monitoring fibrillation process would be necessary to understand the fundamental knowledge about the diseases and further facilitate the research for the drug discovery and disease treatment. In this study, three proto-berberine alkaloids, i.e. berberine, palmatine and coptisine, were examined as three distinctive fluorescent probes to detect amyloid fibrils. These three alkaloids were found to be sensitive to the microenvironment, i.e. viscosity and polarity, with varied fluorescence intensity. They could sensitively probe insulin and lysozyme fibrils with turn-on fluorescence, but did not respond to protein monomers, merited with advantages of larger Stokes shift, greenish-yellow fluorescence and no interference with the fibrillation process. Hydrophobic, electrostatic and hydrogen bond interactions were explored to exist between alkaloids and the fibrils. Moreover, these alkaloids succeeded in monitoring the aggregation process of amyloid proteins in vitro and imaging the fibrils in living cells. The present study demonstrates that the three alkaloids could be the potential candidate fluorescent probes for amyloid fibrils.

Redox Imbalance Triggered Intratumoral Cascade Reaction for Tumor "turn on" Imaging and Synergistic Therapy.

The redox homeostasis in tumors enhances their antioxidant defense ability, limiting reactive oxygen species mediated tumor therapy efficacy. The development of strategies for specific and continuous disruption of the redox homeostasis in tumor cells facilitates the improvement of the cancer therapeutic effect by promoting the apoptosis of tumor cells. Herein, a responsively biodegradable targeting multifunctional integrated nanosphere (HDMn-QDs/PEG-FA) is designed to enhance the anti-tumor efficacy by triggering intratumoral cascade reactions to effectively disrupt intracellular redox homeostasis. Once HDMn-QDs/PEG-FA enters tumor cells, manganese dioxide (MnO2 ) shell on the surface of nanosphere consumes glutathione (GSH) to produce Mn2+ , enabling enhanced chemodynamic therapy (CDT) via a Fenton-like reaction and T1 -weighted magnetic resonance imaging. Meanwhile, the degradation of MnO2 can also cause the fluorescence recovery of quantum dots conjugated on the surface of the shell, realizing "turn-on" fluorescence imaging. In addition, the doxorubicin is released because of the cleavage of the embedded SS bond in the hybrid core framework by GSH. A superior synergistic therapeutic efficiency combined CDT and chemotherapy is shown by HDMn-QDs/PEG-FA in vivo. The tumor-inhibition rate reaches to 94.8% and does not cause normal tissue damage due to the good targeting and tumor microenvironment-specific response.

A ratiometric fluorescence sensor for tetracycline detection based on two fluorophores derived from Partridge tea.

Blue fluorescent carbon dots (PCDs) were prepared by hydrothermal method with Partridge tea. The ethanol extract of Partridge tea (PEE) was found to emit red fluorescence. Thus, a novel ratiometric sensor was constructed by simply mixing the two fluorophores derived from Partridge tea. The presence of tetracycline (TET) at lower concentrations enhanced the emission peak at 508 nm of PCDs and had a negligible effect on the emission peak at 680 nm of PEE. TET at higher concentrations led to  quenching  both the fluorescence of PCDs and PEE via inner filter effect and fluorescence resonance energy transfer, separately. Good linearities for the detection of TET were obtained in the ranges 0.67 to 15.00 µM and 33.33 to 266.67 µM, with limit of detection of 0.095 µM. The sensor was successfully applied to detect TET in lake water and milk samples with good recoveries ranging from 93.27 ± 4.04% to 107.30 ± 6.16%. This study provided a simple, selective, sensitive, rapid, and environmentally friendly method of monitoring TET residues in the environment and food.

Hybrid Micelles of Carbon Quantum Dot-Doxorubicin Conjugates as Nanotheranostics for Tumor Therapy and Turn-On Fluorescence Imaging: Impact of Conjugated Structures and On-Off-On Mechanism.

Carbon quantum dots (CDs) have attracted more and more attention in the field of biological imaging, while their applications are restricted due to their nonspecific fluorescence and small particle size. Herein, two pH-responsive carbon quantum dot-doxorubicin (DOX) conjugates were designed with maleic acid (MA, cis-butenedioic acid) and fumaric acid (FA, trans-butenedioic acid) as linker, respectively, which could self-assemble into unique hybrid micelles as tumor-specific carrier-free nanotheranostics. Owing to the acid-labile covalent modification with conjugated groups and the interaction with the surrounding DOX molecules, the fluorescence of CDs was completely quenched, while it could be recovered in the tumor intracellular microenvironment by acid-triggered cleavage of the fluorophore-drug conjugates, showing excellent turn-on fluorescence for effective cellular imaging. Especially, the trans conjugate with FA as linker possessed higher drug content, better drug release behavior and stronger inhibition of tumor cells than the cis one with MA as linker, demonstrating its promising potential as carrier-free nanotheranostics for future tumor treatment.

A sensitive dual mode turn-on fluorescence and colorimetric nanosensor for ultrasensitive detection of trace amount of gluten proteins in bread products based on crystalline nano cellulose and gold nanoparticles.

In this work, Gold nanoparticles (AuNPs) encapsulated in the surface of crystalline nano cellulose grafted poly citric acid (CNC-g-PCA) and CNC-g-PCA/Au nanocomposite were synthesized successfully that exhibited stable and intense fluorescence property in aqueous buffer. A dual-mode nanosensor is reported with both colorimetric and fluorimetric readout based on citrate-protected AuNPs for discriminative detection of gluten proteins. The proposed sensing system consists of AuNPs and fluorescent CNCs, where CNCs function as a fluorimetric reporter and AuNPs serve a dual function as a colorimetric reporter and fluorescence quencher. The mechanism of the reported dual-mode nanosensor is based on two distance-dependent phenomena, the color change of AuNPs and FRET. The presence of gluten proteins can reverse the process by enlarging the inter-particle distance between AuNPs and CNCs and recovering the fluorescence emission of CNC. The linear range was 0.05 to 0.40 µgmL-1 for UV-vis spectroscopy and 0.017 to 0.298 µgmL-1 for fluorescence spectroscopy, The limit of detection was 4.43 ± 0.019 ngmL-1 for UV-vis spectroscopy and 3.13 ± 0.033 ngmL-1 for fluorescence spectroscopy (n = 6). The fabricated nanosensor was applied to the gluten analysis in gluten-free bread successfully.