Dual-modality Probe Research Articles

Fluorescence-active and peroxidase-like expanded mesoporous silica-encapsulated ultrasmall Pt nanoclusters: a novel colorimetric/fluorescent dual-mode nanosensor for sensitive detection of mercury in medicinal and edible Pueraria lobata.

Anovel colorimetric/fluorescent dual-mode nanosensor for Hg2+ detection was constructed using expanded mesoporous silica (EMSN)-encapsulated ultrasmall platinum nanoclusters (EMSN@Pt NCs) with improved peroxidase-like and stable fluorescent activities. The sensing technique was based on the mechanism that the peroxidase mimetic activity and fluorescence intensity of EMSN@Pt NCs can be inhibited in the presence of Hg2+. In this sensing platform, a linear range of 5-50 nM with a detection limit of 1.78±0.38 nM and quantification limit of 5.93 nM was obtained via fluorescent analysis. Alinear calibration curve from 0.25 to 200 nM with a detection limit of 8.25±0.51 nM and quantification limit of 27.47 nM was achieved via colorimetric analysis. The proposed dual-mode probe possesses excellent selectivity and reliability for Hg2+ detection, which can function as an efficient nanosensor for the quantitative determination of Hg2+ in Pueraria lobata.

11-Mercaptoundecanoic Acid-Functionalized Carbon Dots As a Ratiometric Optical Probe for Doxorubicin Detection

A ratiometric optical dual-mode probe was first designed for the detection of doxorubicin (DOX) based on 11-mercaptoundecanoic acid-functionalized carbon dots (MUA-CDs). The carbon dots (CDs) were synthesized via hydrothermal carbonization of m-phenylenediamine and p-aminobenzoic acid, and then it was reacted with 11-mercaptoundecanoic acid by the amide reaction to obtain the MUA-CDs. The as-synthesized MUA-CDs have a high fluorescence quantum yield (59.4%) with bright green emission. Based on a specific electrostatic interaction and the fluorescence resonance energy transfer (FRET) between MUA-CDs and DOX, a ratiometric optical dual-mode probe was constructed for the detection of DOX with good selectivity, high sensitivity, and excellent anti-interference performance. When DOX was mixed the MUA-CDs, the fluorescence of the MUA-CDs at 513 nm decreased, while the fluorescence at 590 nm increased. With this information, a ratiometric fluorescent method was established to determine DOX with a linear range and limit of detection (LOD) of 0.25–19.96 and 0.66 μM and 50.33–80.88 and 0.23 μM, respectively. Meanwhile, the color of the MUA-CDs varied from colorless to dark yellow in the presence of DOX, and therefore, a ratiometric colorimetric method was applied to determine DOX in a range of 2.50–29.80 μM with a LOD of 0.75 μM. Finally, the as-constructed probe was successfully used to determine DOX in serum, urine, and live cells with satisfactory results. This work will contribute to the specific design of functional CDs and broaden the application of functional CDs in analytical detection and biological imaging.

Aptamer Probes Labeled with Lanthanide-Doped Carbon Nanodots Permit Dual-Modal Fluorescence and Mass Cytometric Imaging.

High‐dimensional imaging mass cytometry (IMC) enables simultaneous quantification of over 35 biomarkers on one tissue section. However, its limited resolution and ultralow acquisition speed remain major issues for general clinical application. Meanwhile, conventional immunofluorescence microscopy (IFM) allows sub‐micrometer resolution and rapid identification of the region of interest (ROI), but only operates with low multiplicity. Herein, a series of lanthanide‐doped blue‐, green‐, and red‐fluorescent carbon nanodots (namely, B‐Cdots(Ln1), G‐Cdots(Ln2), and R‐Cdots(Ln3)) as fluorescence and mass dual‐modal tags are developed. Coupled with aptamers, B‐Cdots(159Tb)‐A10‐3.2, G‐Cdots(165Ho)‐AS1411, and R‐Cdots(169Tm)‐SYL3C dual‐functional aptamer probes, which are then multiplexed with commercially available Maxpar metal‐tagged antibodies for analyzing clinical formalin‐fixed, paraffin‐embedded (FFPE) prostatic adenocarcinoma (PaC) tissue, are further synthesized. The rapid identification of ROI with IFM using fluorescence signals and subsequent multiplexed detection of in situ ROI with IMC using the same tissue section is demonstrated. Dual‐modal probes save up to 90% IMC blind scanning time for a standard 3.5 mm × 3.5 mm overall image. Meanwhile, the IFM provides refined details and topological spatial distributions for the functional proteins at optical resolution, which compensates for the low resolution of the IMC imaging.

Exploring the sensing mechanism in a dual-mode fluorescent probe responding to tryptamine and fluoride ions

The detecting mechanism in a dual-mode fluorescent probe PYNA sensing to tryptamine and fluoride ions has been explored by theoretical methods. The excited state intra-molecular proton transfer (ESIPT) process was investigated through analyzing excited hydrogen bonding changes, potential energy curves, frontier molecular orbitals and the charge density redistribution. Meanwhile, the excited state behaviors of PYNA-F, which is the product of PYNA reacting with fluoride ions, are analyzed to demonstrate the fluorescence detecting mechanism of PYNA for fluoride ions. The experimental new absorption peak of 480 nm has been assigned to the absorption of the anion form of PYNA.

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T 1-T 2 dual-mode magnetic resonance imaging probes.

The T1−T2 dual-mode probes for magnetic resonance imaging (MRI) can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time, making MRI a more flexible imaging modality for complicated applications. In this work, three Gadolinium-diethylene-triaminepentaaceticacid (Gd-DTPA) complex conjugated superparamagnetic iron oxide (SPIO) nanoparticles with different Gd/Fe molar ratio (0.94, 1.28 and 1.67) were prepared as T1–T2 dual-mode MRI probes, named as SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67, respectively. All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3+ chelate stability. SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67. SPIO@PEG-GdDTPA0.94 nanocomposites with r1 (8.4 mM−1s−1), r2 (83.2 mM−1s−1) and relatively ideal r2/r1 ratio (9.9) were selected for T1–T2 dual-mode MRI of blood vessels and liver tissue in vivo. Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner. Importantly, one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h. Overall, the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians, e.g. saving time, lowering side effects and collecting data of different organs sequentially.

Unimolecular chemo-fluoro-luminescent probe for simultaneous detection and imaging of peroxynitrite and hypochlorite in vitro and in vivo

Multicomponent analysis in vitro and in vivo is urgent to study the etiology and optimize therapeutic interventions but remains challenge for designing simple, sensitive and selective optical probes. Herein, by assembling frequently-used sensing moiety (CN isomerization) of fluorescent probe with the same luminophore (fluorescein), a simple unimolecular chemo-fluoro-luminescent probe (Probe-OH) for simultaneous detection of NaClO and ONOO- was designed. Interestingly, the presented probe can be used for direct distinguishing NaClO and ONOO- only by their CL kinetic curves. Moreover, with ultra-sensitive CL signal and real-time fluorescent signal, the dual-mode optical probe was successfully applied for in vitro and in vivo imaging of NaClO and ONOO-. The study not only provides a promising strategy to design simple, sensitive and selective probes for responding multiple targets in vitro and in vivo but also demonstrates the applied potential of CL kinetic curves for discrimination of multiplex analytes.

Organic Framework@Coordination Polymer Core-Shell Composites as Dual-Modal probe for Fluorescence and Colorimetric Analysis of Total Antioxidant Level in Saliva

The total antioxidant level is an important biomarker to determine redox imbalance in human body which can cause many diseases and threaten human health. Though the detection of antioxidants in vivo is gaining wide attention, most of the developed methods have only one detection mode and can only detect single type of antioxidant, leading to inaccurate test results. Here, we developed CuBDC@Fe(III)-ART NPs as a dual-modal probe for water soluble total antioxidants detection in saliva. The detection mechanism was based on two reactions, including a cascading reaction of antioxidants activating the production of free radicals for fluorescence components generated, and a coordination reaction of antioxidants capturing Cu2+ from the MOFs nodes for carboxyl group protonated. Based on this, the UV–vis absorbance intensity and fluorescence intensity of the probes would be simultaneously changed after the incubation with antioxidants. Thus, the probe can detect antioxidants through both UV–vis and fluorescence spectrophotometers. The dual-modal detection method can achieve rapid detection within 10 min with only 200 μL of samples used. Water soluble total antioxidants in saliva with component proportion fluctuated within a certain range can be well detected. And the obtained results were accurate with high recovery. This dual-modal probe provided an accurate, rapid and noninvasive method to detect water soluble total antioxidants in human body.

Nontoxic Gd3+ and Tb3+ co-induced polyelectrolyte nano-aggregates (GTIPAs) for luminescence/magnetic resonance dual-modality imaging

Multimodal nanoprobes are of great significance in clinical diagnosis, because they integrate the advantages of multiple imaging methods. The combination of multiple imaging modes provides more comprehensive and complex information than single-mode imaging, which can greatly improve clinical diagnoses. In this paper, Gd3+ and Tb3+ co-induced polyelectrolyte nanoaggregates (GTIPAs) are introduced as a novel dual-mode imaging probe. Containing gadolinium and terbium, GTIPAs are regular spherical nanoparticles, whose diameters are about 150 nm. As a fluorescent nanomaterial, GTIPAs have strong and stable luminescence intensity. At the same time, as an MRI contrast agent, GTIPAs exhibit a good contrast effect and a high longitudinal relaxation rate. In addition, the polyelectrolytes reduce the cytotoxicity of the complexes, confering excellent biocompatibility and water solubility. Therefore, GTIPAs are non-toxic luminescence/magnetic resonance dual-mode imaging probes.

Synthesis of a Thermal-Responsive Dual-Modal Supramolecular Probe for Magnetic Resonance Imaging and Fluorescence Imaging.

Dual-modal imaging can integrate the advantages of different imaging technologies, which could improve the accuracy and efficiency of clinical diagnosis. Herein, a novel amphiphilic thermal-responsive copolymer obtained from three types of monomers, N-isopropyl acrylamide, 2-(acetoacetoxy) ethyl methacrylate, and propargyl methacrylate, by RAFT copolymerization, is reported. It can be grafted with β-cyclodextrin and aggregation-induced emission (AIE) luminogens tetraphenylethylene by click chemistry and Biginelli reaction. The multifunctional supramolecular polymer (P4) can be constructed by host-guest inclusion between the copolymer and the Gd-based contrast agent (CA) modified by adamantane [Ad-(DOTA-Gd)]. And it can form vesicles with a bilayer structure in aqueous which will enhance the AIE and magnetic resonance imaging effects. As fluorescent thermometer, P4 can enter HeLa cells for intracellular fluorescence imaging (FI) and is sensitive to temperature with detection limit value of 1.5°C. As magnetic resonance CA, P4 exhibits higher relaxation compared to Magnevist, which can prolong the circulation time in vivo. In addition, Gd3+ in the polymer can be quickly released from the body by disassembly that reduced the biological toxicity. This work introduces new synthetic ideas for dual-modal probe, which has great potential for clinical diagnostic applications in bioimaging.

A robust camphor-based colorimetric and fluormetric dual-modal probe with a large Stokes shift for real-time monitoring of endogenous labile Fe2+ in vivo and in vitro

Fe2+ plays a critical role in many physiological processes in the human body. The abnormal level of Fe2+ is implicated in a variety of diseases ranging from anemia to heart failure and even cancer. Herein, a new camphor-derived colorimetric and fluormetric dual-modal probe CCO was constructed for real-time monitoring and imaging of Fe2+ in vitro and vivo. The probe CCO manifested excellent selectivity, superior sensitivity (LOD = 8.3 nM), large Stokes shift (~208 nm), rapid reaction time (<40 s), and remarkable “turn-on” fluorescence response (~21-fold) toward Fe2+ in aqueous solution. With this probe in hand, it is feasible to image the labile Fe2+ supplementation and depletion in living cells. Moreover, this probe was successfully applied to visualize labile Fe2+ generation in living cells and zebrafish larvae under ferroptosis model, which would provide a highly effective tool for in-depth understanding its physiological and pathological functions.

A dual-mode fluorescent probe based on perylene for the detection of Sn2+

A dual-mode fluorescent probe based on perylene, namely N,N'-bis[(2-salicylaldehyde)-ethyl]-3,4,9,10-perylene tetracarboxylicdiimide (SEPTD), has been constructed and synthesized for the detection of Sn2+ in DMF solution. SEPTD exhibited excellent selectivity and sensitivity for detecting Sn2+. The color change of SEPTD was from colerless to yellow in the presence of Sn2+ in DMF solution under 365 nm UV light. The fluorescent intensity of SEPTD was increasing gradually with adding Sn2+. The superior linear response of SEPTD for the concentration of Sn2+ ranged from 50 to 100 μM. The limit of detection (LOD) of SEPTD for the detection of Sn2+ was low to 0.168 μM. The reversibility behavior of SEPTD was investigated. Finally, the mechanism of SEPTD for detecting Sn2+ was investigated by 1H NMR titration and IR spectra.

Characterization of a Hg2+-Selective Fluorescent Probe Based on Rhodamine B and Its Imaging in Living Cells.

A small organic molecule P was synthesized and characterized as a fluorometric and colorimetric dual-modal probe for Hg2+. The sensing characteristics of the proposed probe for Hg2+ were studied in detail. A fluorescent enhancing property at 583 nm (>30 fold) accompanied with a visible colorimetric change, from colorless to pink, was observed with the addition of Hg2+ to P in an ethanol-water solution (8:2, v/v, 20 mM HEPES, pH 7.0), which would be helpful to fabricate Hg2+-selective probes with “naked-eye” and fluorescent detection. Meanwhile, cellular experimental results demonstrated its low cytotoxicity and good biocompatibility, and the application of P for imaging of Hg2+ in living cells was satisfactory.

Preparation of fluorescent bimetallic silver/copper nanoparticles and their utility of dual-mode fluorimetric and colorimetric probe for Hg2+

A dual-mode colorimetric and fluorimetric probe was successfully established based on silver/copper bimetallic nanoparticles (AgCu-BNPs). The AgCu-BNPs were confirmed as individually bimetallic nanoparticles with a mean size of 7.7 ± 0.2 nm, as characterized by high resolution transmission electron microscopy. Intriguingly, the AgCu-BNPs possess both surface plasmon resonances (SPR) and fluorescence emission. AgCu-BNPs emanate bright blue fluorescence with optical emission centered at 442 nm with high quantum yield of 30.3%, and AgCu-BNPs were attenuated or even quenched by Hg2+ via both static and dynamic quenching, coincidently accompanied by a visible color change, which endow AgCu-BNPs a unique utility as dual-mode colorimetric and fluorimetric probes. The detection limits as low as 89 nM and 9 nM were determined by dual-mode of AgCu-BNPs, respectively. The recovery rates in real samples were found to be 97.3–118.8%, and 89.5–112.7% by colorimetric and fluorescent methods separately, demonstrates the good environmental tolerance of the dual-mode probe.

A compact fluorescence/circular dichroism dual-modality probe for detection, differentiation, and detoxification of multiple heavy metal ions via bond-cleavage cascade reactions

Selective detection of multiple analytes in a compact design with dual-modality and theranostic features presents great challenges. Herein, we wish to report a coumarin-thiazolidine masked d-penicillamine based dual-modality fluorescent probe COU-DPA-1 for selective detection, differentiation, and detoxification of multiple heavy metal ions (Ag+, Hg2+, Cu2+). The probe shows divergent fluorescence (FL) /circular dichroism (CD) responses via divergent bond-cleavage cascade reactions (metal ion promoted C-S cleavage and hydrolysis at two distinctive cleavage sites): FL “turn-off” and CD “turn-on” for Ag+ (no hydrolysis), FL “turn-on” and CD “turn-off” for Hg2+ (imine hydrolysis), and FL “self-threshold ratiometric” and CD “turn-off” for excess Cu2+ (lactone and imine hydrolysis), providing the first example of a fluorescence/CD dual-modality probe for multiple species with complimentary responses. Moreover, the bond-cleavage cascade reactions also lead to the formation of d-penicillamine heavy metal ion complexes for potential detoxification treatments.

Europium(III)-Modified Silver Nanoparticles as Ratiometric Colorimetric and Fluorescent Dual-Mode Probes for Selective Detection of Dipicolinic Acid in Bacterial Spores and Lake Waters

Europium(III)-Modified Silver Nanoparticles as Ratiometric Colorimetric and Fluorescent Dual-Mode Probes for Selective Detection of Dipicolinic Acid in Bacterial Spores and Lake Waters

SP-083 - Development of versatile dual-modality imaging probes based on a GRPR antagonist for preoperative imaging and image-guided surgery of prostate cancer

SP-083 - Development of versatile dual-modality imaging probes based on a GRPR antagonist for preoperative imaging and image-guided surgery of prostate cancer

Tetraphenylethylene-conjugated polycation covered iron oxide nanoparticles for magnetic resonance/optical dual-mode imaging.

Magnetic resonance (MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications. To avert aggregation-caused quenching of conventional fluorescence chromophores, an aggregation-induced emission molecule tetraphenylethylene (TPE)-conjugated amphiphilic polyethylenimine (PEI) covered superparamagnetic iron oxide (Alkyl-PEI-LAC-TPE/SPIO nanocomposites) was prepared as an MR/optical dual-mode probe. Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity (352 Fe mM−1s−1) than a commercial contrast agent Feridex (120 Fe mM−1s−1) at 1.5 T. The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE. Reducing alkane chain grafting ratio aggravated the stack of TPE, increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites. Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity. As an MR/optical imaging probe, Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.

Highly sensitive T 1–T 2 dual-mode MRI probe based on ultra-small gadolinium oxide-decorated iron oxide nanocrystals

Single-mode magnetic resonance imaging (MRI) contrast agents (CAs) in clinical settings are easily disturbed by calcification, bleeding, and adipose signals, which result in inaccurate diagnoses. In this study, we developed a highly efficient T 1–T 2 dual-mode MRI CA using an ultra-small gadolinium oxide-decorated magnetic iron oxide nanocrystal (GMIO). The gadolinium element could effectively alter the magnetic properties of the GMIO from soft-ferromagnetism to superparamagnetism. In addition, when the Gd/Fe ratio was 15% (designated as GMIO-2), the GMIO-2 possessed the best superparamagnetism and highest magnetism. Subsequently, T 1 and T 2 values of GMIO-2 were measured through a series of turbo spin-echo images and then multi-spin echo sequence, respectively. Based on this, T 1 and T 2 relaxivities of GMIO-2 were calculated and were the highest (r 1: 1.306 m M−1 s−1 and r 2: 234.5 m M−1 s−1) when compared to other groups. The cytotoxicity of GMIO-2 was negligible under a wide range of dosages, thus exhibiting excellent cell biocompatibility. Moreover, GMIO-2 could quickly diffuse into cells, leading to its effective accumulation. The systemic delivery of GMIO-2 resulted in an excellent T 1–T 2 dual-mode MRI contrast effect in kidneys, which is expected to improve the diagnosis of kidney lesions. Therefore, this work provides a promising candidate for the development of a T 1–T 2 dual-mode MRI CA.

Avant-grade magneto/fluorescent nanostructures for biomedical applications: Organized and comprehensive optical and magnetic evaluation

State-of-the-art core@shell multifunctional nanostructures were prepared that are capable to serve the need of magneto/fluorescent characteristics in a single unit. CdS quantum dots (QD’s) shell was successfully developed upon the SrFe 12O19 nanoparticles core surface and a clear add-on was observed from UV–visible spectroscopy, photoluminescence spectroscopy, VSM and FTIR, with high stability and intactness of core and shell. Optical studies provide in-depth information about development of any new phase at the interface and reject all the possibilities of defects or in core@shell structures. Stoner–Wohlfarth value manifests the single magnetic domain structures for the core@shell nanostructures. Uniaxial anisotropy was achieved with single easy direction. Using water for the synthesis augments the applications zone of these nanostructures specifically in the field of biology. This magnet inside semiconductor model fulfil the need of targeting and tracking at the same time and thus proved to be very useful tool in targeted drug delivery, administer as a dual-modal imaging probe for in vivo multi-photon cell-dynamics, MRI; and cell-sorting applications. Different sets of core/shell nanostructures were synthesized to optimize the best Strontium hexa ferrite (SHF) core loading and shell particle size to achieve finest composition with finest “magneto fluorescent” properties.

Enriched Au nanoclusters with mesoporous silica nanoparticles for improved fluorescence/computed tomography dual-modal imaging.

ObjectivesAu nanoclusters (AuNCs) have been used widely in fluorescence bio‐imaging because of their good fluorescence, small particle size and non‐cytotoxicity. AuNCs are also efficient in computed tomography (CT) imaging. Hence, a dual‐modal imaging probe can be constructed without any complicated modification processes by exploiting the excellent performance of AuNCs. In the present study, AuNCs were enriched with mesoporous silica nanoparticles (MSNs) to obtain enhanced fluorescence/CT dual‐modal imaging, which was capable of acquiring more imaging information for diseases compared with single‐mode imaging.Materials and methodsBiocompatible bovine serum albumin (BSA)‐capped AuNCs were prepared and loaded into amine‐functionalized MSNs to form MSN@AuNCs. BSA‐AuNCs, MSNs, and MSN@AuNCs were characterized by ultraviolet‐visible (UV‐vis) spectra, transmission electron microscopy (TEM), fluorescence spectra, and zeta potential. CT imaging was recorded using micro‐CT scanning. Fluorescence imaging was measured using confocal laser scanning microscopy and flow cytometry.ResultsThe prepared AuNCs and MSNs possessed good properties as previously reported. The fluorescence intensity and CT value of the AuNCs were enhanced after being enriched with MSNs. The nanoparticles were both non‐cytotoxic. Confocal laser scanning microscopy and flow cytometry indicated that MSN@AuNCs in CAL‐27 cells showed improved fluorescence imaging compared with simple AuNCs at the same concentration.ConclusionsThe results revealed that the strategy of enriching AuNCs with MSNs can obtain highly sensitive fluorescence/CT dual‐modal imaging, which indicated the potential of this nanoparticle in the diagnosis and treatment of disease.