Dual-modality Probe Research Articles

A colorimetric and fluorometric dual-mode probe for Cu2+detection based on functionalized silver nanoparticles.

A novel colorimetric/fluorescent probe (AgNPs-GSH-Rh6G2) was prepared by linking silver nanoparticles (AgNPs) with rhodamine 6G derivative (Rh6G2) using glutathione (GSH) as a linker molecule. The prepared probe showed obvious fluorescence change and colorimetric response after adding copper ions. Based on this phenomenon, a colorimetric/fluorescence dual-mode detection method was constructed to recognize copper ions. The linear ranges of fluorescence detection and colorimetric detection were 0.10 to 0.45mM and 0.15 to 0.65mM, respectively, and the limit of detection were 0.18μM and 24.90 μΜ. In addition, the dual-mode probe has achieved satisfactory results in the detection of copper ions in sediment samples. The successful construction of AgNPs-GSH-Rh6G2 not only provide a reliable tool for the detection of copper ions, but also shed light on a new idea for the multi-mode development of the detection platform.

An upconversion fluorescent and colorimetric dual-mode optical probe for triazophos pesticides

A dual-mode optical probe for organophosphorus pesticides triazophos (TRP) was developed on the basis of internal filter effect (IFE) between upconversion nanoparticles NaYF4: Yb/Er @NaYF4@SiO2 (UCNPs) and gold nanoparticles (AuNPs) in the presence of protamine (PRO) and Trypsin (TRY). In this essay, AuNPs can quench significantly the fluorescence intensity of UCNPs at 550 nm with 980 nm excitation. PRO is a cationic protein that binds AuNPs effectively and aggregates AuNPs due to electrostatic attraction. The aggregation of AuNPs made the solution blue and the fluorescence intensity of UCNPs at 550 nm was recovered correspondingly. Furthermore, TRY could hydrolyze PRO, and PRO will reduce AuNPs clustering due to the addition of TRY, inducing the solution to purple and quench the fluorescence of UCNPs again. After adding the TRP, the activity of TRY was inhibited, thereby preventing PRO hydrolysis and causing AuNPs to reaggregate. Reassembled AuNPs restored the fluorescence of UCNPs again. The inhibition efficiency of fluorescence and colorimetric has a good linear relationship with the logarithmic TRP concentration in the range of 0.03∼300 ng/mL, and the detection limits are 0.0052 and 0.0026 ng/mL, respectively. In addition, the recovery of TRP in real food samples with satisfactory results ranged from 96.02 to 104.30% and 95.63 to 105.64%, respectively.

Electrochemiluminescence and electrochemical dual-mode detection of BACE1 activity based on the assembly of peptide and luminol co-functionalized silver nanoparticles induced by cucurbit[8]uril

A novel electrochemiluminescence (ECL) and electrochemical dual-mode sensor was developed for detecting the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and screening its inhibitor. Specifically, the adamantane (ADA)-functionalized peptide (P1), a designed substrate peptide for BACE1, was immobilized on the electrode surface via host-guest interaction between β-cyclodextrin (β-CD) and ADA. The aggregation of the peptide (P2) and luminol co-functionalized silver nanoparticles could be induced by cucurbit [8]uril (CB[8] due to the ability of CB[8] to accommodate two aromatic residues simultaneously. The obtained (CB[8]-P2-AgNPs-luminol)n aggregates with both ECL and electrochemical activity, used as the dual-mode signal probe, could be captured to the N-terminal of P1 through CB[8]. Once the substrate P1 was cleaved by BACE1, the probe-binding polypeptide fragment detached from the electrode surface, resulting in a remarkable decrease in the ECL and electrochemical signals. Taking advantage of the signal amplification function of the signal probe, the sensitive dual-mode assay for BACE1 activity can be achieved with the low detection limits of 33.11 pM for ECL and 53.19 pM for electrochemical mode. The superior analytical performance of this novel dual-mode sensor toward BACE1 activity suggested the promising application in early diagnosis of Alzheimer's disease (AD).

Rational development of a peptide-based probe for fluorescence and colorimetric dual-mode detection of Cu2+ and S2− ions: Real application in cell imaging and test strips

A new dual-mode probe FAM-SSH with fluorescence and colorimetric properties was developed by solid-phase peptide synthesis, comprising 5-carboxy fluorescein (5-FAM) as a fluorophore, and tripeptide (Ser-Ser-His) as a recognition group. FAM-SSH not only displayed highly selective detection of Cu2+ based on fluorescence quenching mode, but also achieved colorimetric recognition of Cu2+ in solution, wherein a color change was observable to the naked eye. Additionally, the FAM-SSH-Cu2+ ensemble was highly selective for S2− over a wide pH range (7.0–12.0), characterized by a fluorescence enhanced response and colorimetric recognition, which was caused by the release of FAM-SSH and the precipitation of CuS. Moreover, the limit of detection (LOD) values for Cu2+ and S2− were 55.5 nM and 31.1 nM, respectively. Results of sample analyses and cell imaging experiments indicated that FAM-SSH has exciting field practicability and good cell permeability, and would be further useful for detection and imaging in environmental systems and living cells. Finally, test strips were produced by immersing them in FAM-SSH solution, thereby creating a method for portable visual detection. More importantly, a smartphone-assisted visual sensing platform was also developed for semi-quantitative Cu2+ and S2− detection with LOD values of 0.48 μM and 1.22 μM, respectively.

Cathepsin K-Activated Probe for Fluoro-Photoacoustic Imaging of Early Osteolytic Metastasis.

Precise detection of early osteolytic metastases is crucial for their treatment but remains challenging in the clinic because of the limited sensitivity and specificity of traditional imaging techniques. Although fluorescence imaging offers attractive features for the diagnosis of osteolytic metastases, it is hampered by limited penetration depth. To address this issue, a fluoro-photoacoustic dual-modality imaging probe comprising a near-infrared dye caged by a cathepsin K (CTSK)-cleavable peptide sequence on one side and functionalized with osteophilic alendronate through a polyethylene glycol linker on the other side is reported. Through systematic in vitro and in vivo experiments, it is demonstrated that in response to CTSK, the probe generated both near-infrared fluorescent and photoacoustic signals from bone metastatic regions, thus offering a potential strategy for detecting deep-seated early osteolytic metastases.

Exploring multi-element co-doped carbon dots as dual-mode probes for fluorescence/CT imaging

Osteosarcoma (OS), the most common pediatric malignant bone tumor, has been stagnant in its current treatment status due to its highly heterogeneous, aggressive, and lethal nature. Herein, we developed multi-element charge-transfer co-doped carbon dots (CDs) as dual-mode contrast agents for OS models using hydrothermal carbonization. The obtained P, W co-doped CDs, P, W, Hf co-doped CDs-1, and P, W, Hf co-doped CDs-2 have high long-wavelength quantum yields (16.5, 27.3, and 14.2%) in N, N-dimethylformamide solution, which can be attributed to the presence of valence electrons in the doped metal ions or metal hydrochloride, which promotes the radiative recombination of electrons and the formation of holes. Moreover, P, W, Hf co-doped CDs-1 exhibited higher biocompatibility, good 143B cell imaging, and fluorescence/CT high contrast imaging performance in Balb/C tumor-bearing mice compared to P, W co-doped CDs, and P, W, Hf co-doped CDs-2. In addition, the biodistribution and pharmacokinetic results further indicate that P, W, Hf co-doped CDs-1 has apparent advantages in imaging tracking and biosafety of OS and has excellent potential as a dual-mode imaging contrast agent.

A dual-mode fluorescent probe based on carbon dots for detecting solution polarity.

Fluorescent probes always attract huge attention. In particular, carbon dots, due to their unique biocompatibility and variable fluorescence characteristics, can be used in multiple fields and were fulled of expectation by researchers. Since the advent of the dual-mode carbon dots probe, which greatly improved the accuracy of quantitative detection, there are higher hopes for dual-mode carbon dots probes. Herein, we have successfully developed a new dual-mode fluorescent carbon dots probe based on 1,10-phenanthroline (Ph-CDs). Ph-CDs detect the object to be measured based on both down-conversion luminescence and up-conversion luminescence at the same time, different from the reported dual-mode fluorescent probes which are based on the wavelength and intensity changes in down-conversion luminescence. As-prepared Ph-CDs have good linear relationships with the polarity of solvents in down-conversion luminescence (R2=0.9909) and up-conversion luminescence (R2=0.9374), respectively. Hence, Ph-CDs provide a new in-depth insight into the design of fluorescent probes with dual-mode detection and they can give more accurate, reliable and convenient detection results.

Xylenol orange-modified CdTe quantum dots as a fluorescent/colorimetric dual-modal probe for anthrax biomarker based on competitive coordination

Bacillus anthracis spores can make humans infected with vicious anthrax, so it is significant to detect their biomarker 2,6-pyridinedicarboxylic acid (DPA). The development of dual-modal methods for DPA detection that are more flexible in practical applications remains a challenge. Herein, colorimetric xylenol orange (XO) was modified on fluorescent CdTe quantum dots (QDs) for dual-modal detection of DPA through competitive coordination. After the binding of XO on CdTe QDs via coordination with Cd2+, CdTe QDs displayed quenched red fluorescence and the bound XO was presented as red color. The competitive coordination of DPA with Cd2+ made XO released from CdTe QDs, causing the enhanced red fluorescence of CdTe QDs and the yellow color of free XO. On this basis, DPA was rapidly (1 min) quantified through fluorescent and colorimetric modes within the ranges of 0.1–5 μM and 0.5–40 μM, respectively. The detection limits for DPA were calculated as low as 42 nM and 240 nM, respectively assigned to fluorescent and colorimetric modes. The level of urinary DPA was further measured. Satisfactory relative standard deviations (fluorescent mode: 0.1%–10.2%, colorimetric mode: 0.8%–1.8%) and spiked recoveries (fluorescent mode: 100.0%–115.0%, colorimetric mode: 86.0%–96.6%) were obtained.

Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.

Sulfatase is an important biomarker closely associated with various diseases. However, the state-of-the-art sulfatase probes are plagued with a short absorption/emission wavelength and limited sensitivity. Developing highly sensitive fluorescent probes for in vivo imaging of sulfatase remains a grand challenge. Herein, for the first time, an activatable near-infrared fluorescence/photoacoustic (NIRF/PA) dual-modal probe (Hcy-SA) for visualizing sulfatase activity in living cells and animals is developed. Hcy-SA is composed of a sulfate ester moiety as the recognition unit and a NIR fluorophore hemicyanine (Hcy-OH) as the NIRF/PA reporter. The designed probe exhibits a rapid response, excellent sensitivity, and high specificity for sulfatase detection in vitro. More importantly, cells and in vivo experiments confirm that Hcy-SA can be successfully applied for PA/NIRF dual-modal imaging of sulfatase activity in living sulfatase-overexpressed tumor cells and tumor-bearing animals. This probe can serve as a promising tool for sulfatase-related pathological research and cancer diagnosis.

A dual-modality hydrogen sulfide-specific probe integrating chemiluminescence with NIR fluorescence for targeted cancer imaging

A dual-modality hydrogen sulfide-specific probe integrating chemiluminescence with NIR fluorescence for targeted cancer imaging

Synergism of Photo-Induced Electron Transfer and Aggregation-Induced Quenching Mechanisms for Highly Sensitive Detection of Silver Ion and Captopril.

Carbon-based nanoprobes, with excellent physicochemical performance and biocompatibility, are a kind of ideal nanomaterial for biosensing. Herein, we designed and prepared novel oxygen-doped nitrogen-enrichment carbon nanoribbons (ONCNs) with an excellent optical performance and uniform morphology, which could be used as a dual-mode fluorescence probe for the detection of Ag+ ion and captopril (Ctl) based on the synergism of photo-induced electron transfer and aggregation-induced quenching mechanisms. By recording the changes in fluorescent intensities of ONCNs, the Ag+ ion and Ctl concentrations can be easily tested in real samples. The results displayed that two good linear relationships existed between the change in fluorescent intensity of ONCNs and the concentrations of Ag+ ion and Ctl in the ranges of 3 μM to 30 μM and 1 μM to 30 μM, with the detection limit of 0.78 µM and 74 nM, respectively. The proposed sensing platform has also been successfully applied for the Ctl analysis in commercial tablet samples based on its high selectivity, proving its value in practical applications.

Fe3O4-rhodamine 6G nanoparticles: An iron enhanced pH sensitive multimodal probe for fluorescence and magnetic resonance imaging of tumor cell

The accurate diagnosis of tumor at the early stage depends on efficient medical imaging methods using probes with high sensitivity to the environment of tumor cells. For this purpose, we design the Fe3O4-rhodamine 6 G (Rh6G) nanoparticles (NPs) as a kind of dual-mode probe for fluorescence and magnetic resonance imaging (MRI). The Fe3O4-Rh6G NPs are demonstrated to be Fe3+ enhanced and pH-sensitive fluorescent agents, and the strongest fluorescence performance occurs under the pH value of 3. Cytotoxicity assessment in HeLa cells proves the good biocompatibility and low toxicity of the Fe3O4-Rh6G NPs. The consequent fluorescence experiments in tumor cells show good imaging contrast, which is contributed by both the Fe3+ released from Fe3O4 and the acid environment of tumor cells. Moreover, the Fe3O4-Rh6G NPs are superparamagnetic and have a strong MRI T2 contrast effect. According to the performance in fluorescence and MRI tests, the Fe3O4-Rh6G NPs are potential dual-mode probes for MRI contrast agents and fluorescence probes with high biocompatibility for early-stage tumor detection.

Ratiometric H2S probe that can be recognized by the naked eye and its application in cell imaging

A ratiometric dual-mode probe NI-SH based on 1,8-Naphthalimide was prepared for H2S detection. When treated with H2S, the fluorescence of NI-SH changes from blue (456 nm) to green (540 nm), and displays significant color variation (colorless to yellow) that can visible to the naked eye. Further investigation shows that the NI-SH has high sensitivity, selectivity, and low detection limit at about 0.2 μM, and with large Stokes shift (84 nm). The intermolecular charge transfer (ICT) response mechanism of NI-SH was further studied by analyzing the distributions of the molecular orbital. Besides, NI-SH exhibits a ratiometric fluorescence response in living Hela cells.

Pre- and Intraoperative Visualization of GRPR-Expressing Solid Tumors: Preclinical Profiling of Novel Dual-Modality Probes for Nuclear and Fluorescence Imaging

Image-guided surgery using a gastrin-releasing peptide receptor (GRPR)-targeting dual-modality probe could improve the accuracy of the resection of various solid tumors. The aim of this study was to further characterize our four previously developed GRPR-targeting dual-modality probes that vary in linker structures and were labeled with indium-111 and sulfo-cyanine 5. Cell uptake studies with GRPR-positive PC-3 cells and GRPR-negative NCI-H69 cells confirmed receptor specificity. Imaging and biodistribution studies at 4 and 24 h with 20 MBq/1 nmol [111In]In-12-15 were performed in nude mice bearing a PC-3 and NCI-H69 xenograft, and showed that the probe with only a pADA linker in the backbone had the highest tumor-to-organ ratios (T/O) at 24 h after injection (T/O > 5 for, e.g., prostate, muscle and blood). For this probe, a dose optimization study with three doses (0.75, 1.25 and 1.75 nmol; 20 MBq) revealed that the maximum image contrast was achieved with the lowest dose. Subsequently, the probe was successfully used for tumor excision in a simulated image-guided surgery setting. Moreover, it demonstrated binding to tissue sections of human prostate, breast and gastro-intestinal stromal tumors. In summary, our findings demonstrate that the developed dual-modality probe has the potential to aid in the complete surgical removal of GRPR-positive tumors.

Contractile Hairpin DNA-Mediated Dual-Mode Strategy for Simultaneous Quantification of Lactoferrin and Iron Ion by Surface-Enhanced Raman Scattering and Fluorescence Analysis.

DNA-mediated self-assembly technology with good sensitivity and affinity ability has been rapidly developed in the field of probe sensing. The efficient and accurate quantification of lactoferrin (Lac) and iron ions (Fe3+) in human serum and milk samples by the probe sensing method can provide useful clues for human health and early diagnosis of anemia. In this paper, contractile hairpin DNA-mediated dual-mode probes of Fe3O4/Ag-ZIF8/graphitic quantum dot (Fe3O4/Ag-ZIF8/GQD) NPs were prepared to realize the simultaneous quantification of Lac by surface-enhanced Raman scattering (SERS) and Fe3+ by fluorescence (FL). In the presence of targets, these dual-mode probes would be triggered by the recognition of aptamer and release GQDs to produce FL response. Meanwhile, the complementary DNA began to shrink and form a new hairpin structure on the surface of Fe3O4/Ag, which produced hot spots and generated a good SERS response. Thus, the proposed dual-mode analytical strategy possessed excellent selectivity, sensitivity, and accuracy due to the dual-mode switchable signals from "off" to "on" in SERS mode and from "on" to "off" in FL mode. Under the optimized conditions, a good linear range was obtained in the range of 0.5-100.0 μg/L for Lac and 0.01-5.0 μmol/L for Fe3+ and with detection limits of 0.14 μg/L and 3.8 nmol/L, respectively. Finally, the contractile hairpin DNA-mediated SERS-FL dual-mode probes were successfully applied in the simultaneous quantification of iron ion and Lac in human serum and milk samples.

Dual Chemiexcitation by a Unique Dioxetane Scaffold Gated by an OR Logic Set of Triggers.

Chemiexcitation of phenoxy-1,2-dioxetane chemiluminescent luminophores is initiated by electron transfer from a meta-positioned phenolate ion to the peroxide-dioxetane bond. Here we report the development of a unique 1,2-dioxetane chemiluminescent scaffold with chemiexcitation gated by an OR logic dual-set of triggering events. This scaffold is composed of meta-dihydroxyphenyl-1,2-dioxetane-adamantyl molecules, equipped with acrylic acid and chlorine substituents, that chemiexcitation under physiological conditions. A dual-mode chemiluminescent probe, armed with two different triggering substrates designed for activation by the enzymes β-galactosidase and alkaline phosphatase, was synthesized. The probe emitted intense light signals in the response to each enzyme, demonstrating its ability to serve as a single-component chemiluminescent sensor for dual-analyte detection. We also demonstrated the ability of the probe to detect β-galactosidase and phosphatase activities in bacteria. This is the first 1,2-dioxetane scaffold capable of responding to two different chemiexcitation events from two different positions on the same dioxetane molecule. We anticipate that the OR-gated mode of chemiexcitation, described herein, will find utility in the preparation of chemiluminescent probes with a dual-analyte detection/imaging mode.

Dual-mode supramolecular fluorescent probe for rapid and on-site detection of chlorpyrifos in the environment

Chlorpyrifos (CPF) as a classic organophosphorus pesticide has been widely used in agricultural applications to control insects and worms. CPF in the environment can cause deaths of diverse kinds of aquatic organism and bring a high risk to human health. Therefore, the development of effective analytical method for CPF is of great importance. In this work, a novel dual-mode albumin (ALB)-based supramolecular probe FD@ALB was designed and prepared for rapid detection of CPF in the environment. The limit of detection is 0.57 μM (∼ 0.2 ppm) with a wider detection range up to 200 μM, which is satisfactory for application. The sensing mechanism can be ascribed to CPF-induced phosphorylation of ALB, thus leading to a change in the binding microenvironment of FD dye. Moreover, the paper-based test strips were used in conjunction with the FD@ALB, realizing the portable detection of CPF. This method was demonstrated to be suitable for on-site detection of CPF in various kinds of environmental samples, including water, soil, and food samples, with the aid of a smartphone. To the best of our knowledge, this is the first analytical method achieving a combination of the rapid and ratiometric detection of CPF in the environment.

A robust ratiometric photoacoustic and fluorescence dual-modal molecular probe for capturing endogenous HNO generation in tumor mice model

HNO is reported in association with a wide variety of physiological and pathological states. However, photoacoustic (PA)/fluorescence (FL) dual-modal probes with complementary advantages for detection of HNO in living systems, especially in tumors, are still lacking. Herein, the first near-infrared (NIR) ratiometric PA/FL dual-modal probe (DOP-HNO), composed of a dual ratiometric molecular skeleton caged with 2-(diphenylphosphino)-benzoate group, was designed and synthesized for capturing endogenous HNO generation in vivo. DOP-HNO was able to specifically and sensitively respond to HNO with 4-fold ratiometric fluorescence enhancement (F783/F720) and 2.6-fold ratiometric PA enhancement (PA740/PA670). Moreover, DOP-HNO successfully visualized HNO fluctuations in 4T1 cells and living mice, and the crosstalk between NO and H2S in the tumors of living mice was clearly observed through NIR dual-ratiometric PA/FL imaging, indicating the accurate detection of HNO in vivo. More importantly, using DOP-HNO, for the first time, we provided the visualization evidence of endogenous HNO generation in cancer model and further investigated its possible generation mechanisms by H2S/NO interaction. Thus, we envision that the dual-modal probe DOP-HNO will be an effective tool to study the complex relationship between HNO and cancer as well as the pathology of other HNO-related diseases.

Neuropilin 1-targeted near-infrared fluorescence probes for tumor diagnosis

Two neuropilin 1 (NRP1)-targeted near-infrared fluorescence probes for tumor imaging were synthesized via click reaction. These two probes achieve excellent solubility and less aggregation. Importantly, they were able to rapidly target NRP1-overexpressing tumors and had long retention within tumors. Additionally, QS-1 with appropriate hydrophilicity displays higher tumor to muscle (T/M) ratio. And QS-1 can be easily modified with other functional group, and serve as a platform for constructing dual-modal or dual-targeting probes.

Intracerebral Fluorescence-Photoacoustic Dual-Mode Imaging for Precise Diagnosis and Drug Intervention Tracing in Depression.

Unravelling the pathophysiology of depression is a unique challenge. Depression is closely associated with reduced norepinephrine (NE) levels; therefore, developing bioimaging probes to visualize NE levels in the brain is a key to elucidating the pathophysiological process of depression. However, because NE is similar in structure and chemical properties to two other catecholamine neurotransmitters, epinephrine and dopamine, designing an NE-specific multimodal bioimaging probe is a difficult task. In this work, we designed and synthesized the first near-infrared fluorescent-photoacoustic (PA) dual-modality imaging probe for NE (FPNE). The β-hydroxyethylamine of NE was shown to react via nucleophilic substitution and intramolecular nucleophilic cyclization, resulting in the cleavage of a carbonic ester bond in the probe molecule and release of a merocyanine molecule (IR-720). This process changed the color of the reaction solution from blue-purple to green, and the absorption peak was red-shifted from 585 to 720 nm. Under light excitation at 720 nm, linear relationships between the concentration of NE and both the PA response and the fluorescence signal intensity were observed. Thus, the use of intracerebral in situ visualization for diagnosis of depression and monitoring of drug interventions was achieved in a mouse model by fluorescence and PA imaging of brain regions after administration of FPNE by tail-vein injection.