Dual-modality Probe Research Articles

Colorimetric/SERS dual-mode detection of mercury ion via SERS-Active peroxidase-like Au@AgPt NPs

The development of mercury ion (Hg2+) probes integrating the ability of facile preliminary evaluation and high-sensitive accurate assay with wide detection range is very important for water pollution prevention and human health. Herein, a novel colorimetric/SERS dual-mode detection of Hg2+ was proposed by using the SERS-active peroxidase-like Au@AgPt NPs. The Au@AgPt NP has hexoctahedral Au nanoparticle core with edges coating by Pt, which shows good SERS activity of Au and enhanced catalyst activity of Pt for designing colorimetric/SERS dual-mode probes. Basing on the colorimetric assay, 5 μM–1 mM Hg2+ can be facile observed by naked eye and a linear sensing (1 μM–100 μM) with limit of detection (LOD) of 0.52 μM was obtained by absorption analysis. Besides, a linear calibration curve from 1 nM to 10 μM was achieved by SERS with LOD of 0.28 nM. The proposed dual-mode probes with good selectivity and reliability integrate the advantages of facile detection by colorimetric analysis and high-sensitive trace assay by SERS, and possess relatively better performance on sensitivity and detection range in comparison to the previous probes/methods, which can be served as efficient probes for monitoring water quality.

Red aggregation-induced emission luminogen and Gd3+ codoped mesoporous silica nanoparticles as dual-mode probes for fluorescent and magnetic resonance imaging

Fluorescence imaging and magnetic resonance imaging have been research hotspots for adjuvant therapy and diagnosis. However, traditional fluorescent probes or contrast agents possess insurmountable weaknesses. In this work, we reported the preparation of dual-mode probes based on mesoporous silica nanomaterials (MSNs), which were doped with an aggregation-induced emission (AIE) dye and Gd3+ through a direct sol-gel method. In this system, the obtained materials emitted strong red fluorescence, in which the maximum emission wavelength was located at 669 nm, and could be applied as effective fluorescence probes for fluorescence microscopy imaging. Furthermore, the introduction of Gd3+ made the nanoparticles effective contrast agents when applied in contrast-enhanced magnetic resonance (MR) imaging because they could improve the contrast of MR imaging. The excellent biocompatibility of these nanoparticles, as demonstrated via a typical CCK-8 assay, and their performance in fluorescence cell imaging and MR imaging shows their potential for applications in biomedical imaging.

In Situ Fluorescent and Photoacoustic Imaging of Golgi pH to Elucidate the Function of Transmembrane Protein 165

Golgi pH homeostasis affects many different biological processes, including glycosylation. Recent studies have demonstrated that transmembrane protein 165 (TMEM165) deficiency leads to Golgi glycosylation abnormalities by disturbing Golgi pH homeostasis. However, due to the lack of specific tools to measure Golgi pH in situ, evidence for TMEM165 involvement in H+ transport in the Golgi apparatus is still absent. Herein, the photoacoustic and fluorescent dual-mode probe CPH was developed for ratiometric detection of Golgi pH. CPH was proved to accumulate in the Golgi apparatus and reversibly image Golgi pH in real-time with high sensitivity in cells. Furthermore, we found that the absence of TMEM165 influenced H+ equilibrium and caused Golgi apparatus acidification. Our work provides strong evidence that TMEM165 regulates Golgi pH homeostasis. Moreover, we believe that CPH has the potential to be a practical tool to monitor Golgi pH in various biological processes.

NIR Scaffold Bearing Three Handles for Biocompatible Sequential Click Installation of Multiple Functional Arms

Near-infrared (NIR) probes are ideal for fluorescence labeling and imaging of biological targets in living animals. However, the instability of common NIR dyes hampers the construction of NIR probes bearing multiple functional components such as biomolecules for specific targeting and imaging reagents for multimodality imaging. To overcome these limitations, we designed a novel NIR scaffold bearing two terminal alkynes as clickable handles and a chloride on the heptamethine backbone that allows nucleophilic substitution with an azide to generate the third clickable handle. This unique scaffold allows for facile installation of multiple functional arms for the construction of multifunctional NIR probes. Various biomacromolecules or imaging reagents can be introduced to the NIR scaffold by sequential one-pot click reactions under biocompatible conditions. The preclickable handle chloride on the NIR backbone does not interfere with the initial click reactions, and it can be easily transformed into an azide for a following click reaction. On the basis of this unique NIR scaffold, we developed a highly efficient method to construct diverse NIR probes containing multiple functional biomolecules including peptides, antibodies, nucleic acids, and NIR/PET (positron emission tomography) dual-modality imaging probes bearing tumor-targeting groups. NIR imaging or multimodality imaging using these probes was performed on live cells or tumor models on living mice.

Dual-modality probe based on black phosphorous and NiFe2O4 NTs for electrochemiluminescence and photothermal detection of ovarian cancer marker

An electrochemiluminescence and photothermal immunosensor based on a dual-modality integrated probe was proposed for sensitive and reliable detection of lipolysis stimulated lipoprotein receptor (LSR), a new biomarker of ovarian cancer. Black phosphorous quantum dots (BPQDs) possess fascinating electrochemical property and unique photothermal effect, which could not only enhance ECL signal of N-(4-aminobutyl)-N-ethylisoluminol (ABEI) through accelerating dissolved O2 evolution but also realize temperature signal output by converting laser energy into heat. Furthermore, NiFe2O4 nanotubes (NiFe2O4 NTs) have large specific surface area and favorable adsorption ability, which could increase the immobilized amount of ABEI and BPQDs, further strengthening ECL and temperature signal. As a result, a dual-mode immunosensor was constructed and realized ECL and temperature dual signal to detect LSR, making the results more reliable. This work provided a new thought for the development of sensitive and accurate sensors and was expected to employ for determination of other biomarkers.

Smart dual T1 MRI-optical imaging agent based on a rhodamine appended Fe(III)-catecholate complex.

A rhodamine appended Fe(iii)-catecholate complex Fe(RhoCat)3 is reported as a smart dual-modal T1 MRI-optical imaging probe. The high spin Fe(iii) coordination sphere and rhodamine unit act as MRI and optical reporters, respectively. The probe showed a r1-relaxivity of 4.37 mM-1 s-1 at 1.41 T via the interaction of second sphere water molecules to coordinated oxygen atoms. It produced an enhanced signal intensity of phantom images on the 7.0 T animal research MRI/MRS scanner at 25 °C and pH 7.3. The interaction of the probe with bovine serum albumin (BSA) significantly improved r1 relaxivity (7.09 mM-1 s-1). Moreover, the optical imaging reporter rhodamine moiety exhibited sensitivity towards biomolecule nitric oxide (NO) and acidic pH via the formation of a ring-opened tautomer of rhodamine, wherein the r1 relaxivity of the probe was enhanced to 5.19 mM-1 s-1 for NO and slightly decreased for acidic pH. Further, the probe visualized NO in adenocarcinoma gastric (AGS) cells via a turn-on fluorescence mechanism with 80% cell viability. Thus, Fe(RhoCat)3 is demonstrated as a potential dual "MRI-ON and Fluorescence-ON" molecular imaging probe to visualize the NO molecule and acidic pH in the tumour microenvironment.

Imaging of peroxynitrite in drug-induced acute kidney injury with a near-infrared fluorescence and photoacoustic dual-modal molecular probe.

A FRET-based probe for mapping the fluctuation of ONOO- in cisplatin-induced acute kidney injury was constructed. It exhibits ratiometric near infrared fluorescence and a dramatic decrease of its peak absorbance at 719 nm upon addition of ONOO- that is converted into remarkable signal changes in fluorescence and photoacoustic images respectively.

Hyaluronan-directed fabrication of co-doped hydroxyapatite as a dual-modal probe for tumor-specific bioimaging.

In recent years, nano-hydroxyapatite (nHAp) based dual-/multi-modal bioimaging systems have received significant attention due to their excellent bioactivity and biocompatibility. Specifically, co-doping two or more ions (such as Eu3+, Te3+, Gd3+ and Mn2+) into the lattice of nHAp can directly endow nHAp with multimodal imaging properties. However, the main strategy for the construction of co-doped nHAp nanocrystals depends on high temperature and techniques of post-modification, which could lead to inevitable nHAp crystal polymerization and increased particle size. Thus, the complexity of the preparation could further limit the clinical applications. Herein, based on the specific binding between hyaluronan and CD44 protein, a biomimetic synthesis method using hyaluronan as a template was explored for the construction of Eu/Ba co-doped and F-substituted nHAp (HA@nFAp:Eu/Ba) with recognition capability. The as-prepared HA@nFAp:Eu/Ba nanocrystals possessed uniform and spindle-like morphology with good monodispersity. Compared with co-doped nFAp that was synthesized under hyaluronan-free and high-temperature hydrothermal conditions, this one-step synthesized HA@nFAp:Eu/Ba presented improved doping efficiency and colloidal stability, realizing high sensitivity in both CT and fluorescence imaging. Besides, cytotoxicity studies indicated that the developed HA@nFAp:Eu/Ba nanocrystals exhibited good compatibility in both cells and mice. Meanwhile, the HA@nFAp:Eu/Ba nanocrystals also demonstrated tumor targeted stability in both cancer cells and living mice according to the favourable results from CT and fluorescence imaging. Therefore, this biomimetic synthesis strategy allowed multi-functionalization of nHAp in one pot under mild conditions.

Orange-emitting N-doped carbon dots as fluorescent and colorimetric dual-mode probes for nitrite detection and cellular imaging.

Novel orange-emitting N-doped carbon dots (N-CDs) were prepared as fluorescent and colorimetric dual-mode probes for sensing nitrite (NO2-). The obtained N-CDs possessed fantastic optical properties and specific responses to NO2-. NO2- could induce the fluorescence static quenching of N-CDs, and a linear relationship was obtained in the range from 2 to 60 μM with the detection limit of 0.35 μM. More interestingly, the N-CDs exhibited ratiometric absorption signals with visible color conversion (red-purple), which allowed the development of a simple colorimetric method for NO2- monitoring in the linear range of 2-80 μM with a detection limit down to 0.13 μM. Additionally, the N-CDs were capable of monitoring NO2- in the A549 cells, which indicated their great potential in biosensing.

A novel clickable MSAP agent for dual fluorescence/nuclear labeling of biovectors.

We herein describe the development of a novel dual-modality optical/radio-imaging agent for general and site-specific labeling of biovectors through a 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. The CBT-based multifunctional single-attachment-point (MSAP) agent enables a single-step synthesis of various dual-modality probes characterized by rapid conjugation, high labeling yields, metabolically stable products and applicability to orthogonal two-step labeling of sensitive biomolecules. In addition, the two-step radiolabeling protocol and click reaction were optimized by using CBT scavengers to improve the reaction rate and molar activity of the imaging probes. Our methodology allows for a simple and efficient synthetic route to produce a variety of dual-modality imaging agents for preoperative surgical planning and intraoperative surgical guidance.

Ultrasound/Optical Dual-Modality Imaging for Evaluation of Vulnerable Atherosclerotic Plaques with Osteopontin Targeted Nanoparticles.

Because of the high mortality of coronary atherosclerotic heart diseases, it is necessary to develop novel early detection methods for vulnerable atherosclerotic plaques. Phenotype transformation of vascular smooth muscle cells (VSMCs) plays a vital role in progressed atherosclerotic plaques. Osteopontin (OPN) is one of the biomarkers for phenotypic conversion of VSMCs. Significant higher OPN expression is found in foam cells along with the aggravating capacity of macrophage recruitment due to its arginine-glycine-aspartate sequence and interaction with CD44. Herein, a dual-modality imaging probe, OPN targeted nanoparticles (Cy5.5-anti-OPN-PEG-PLA-PFOB, denoted as COP-NPs), is constructed to identify the molecular characteristics of high-risk atherosclerosis by ultrasound and optical imaging. Characterization, biocompatibility, good binding sensibility, and specificity are evaluated in vitro. For in vivo study, apolipoprotein E deficien (ApoE-/- ) mice fed with high fat diet for 20-24 weeks are used as atherosclerotic model. Ultrasound and optical imaging reveal that the nanoparticles are accumulated in the vulnerable atherosclerotic plaques. OPN targeted nanoparticles are demonstrated to be a good contrast agent in molecular imaging of synthetic VSMCs and foam cells, which can be a promising tool to identify the vulnerable atherosclerotic plaques.

Polydopamine-coated downconversion nanoparticle as an efficient dual-modal near-infrared-II fluorescence and photoacoustic contrast agent for non-invasive visualization of gastrointestinal tract in vivo

Herein, a multifunctional dual-modal imaging probe is successfully developed to integrate the advantages of second near-infrared window (NIR-II, 1000–1700 nm) fluorescence imaging (FI) and photoacoustic imaging (PAI) with the ultimate goal of improving diseases diagnosis and management. Melanin-inspired polydopamine (PDA) polymer coated NaYF4:Yb3+,Er3+@NaYbF4@NaYF4:Nd3+ down conversion nanoparticles (DCNPs) is designed via water-in-oil microemulsion method, which comprises a DCNP core, acting as the NIR-II optical imaging agent, and a PDA shell, acting as the PA contrast agent. By taking the advantages of high spatial resolution and excellent temporal resolution, the dual-modal contrast agent is capable for high sensitivity real-time visualization of gastrointestinal tract, diagnosis of gastrointestinal peristalsis disorder and NIR-II FI-guided intestinal obstruction surgery. All of the above results demonstrate the great potential of DCNP@PDA NP as an efficient NIR-II/PAI dual-modal contrast agent for precision medicine.

Black phosphorus quantum dots functionalized MXenes as the enhanced dual-mode probe for exosomes sensing

Exosomes are nanoscale extracellular vesicles and have proven to be an effective biomarker for early cancer diagnosis. In this work, an ECL and photothermal dual-mode biosensor was fabricated for exosomes detection by utilizing emerging materials black phosphorous quantum dots (BPQDs) and MXenes as signal amplifier. To be specific, BPQDs can catalyze the oxidization of Ru(dcbpy)32+ and was for the first time used as coreactant, the prepared self-enhanced Ru(dcbpy)32+@BPQDs ECL system can produce a strong ECL signal by reducing energy loss and shortening electron transfer distance. MXenes possess large specific surface area and outstanding conductivity, which was employed as supporter to increase the immobilization amount of Ru(dcbpy)32+ and BPQDs, further enhanced ECL signal. Furthermore, BPQDs and MXenes both have excellent photothermal effect, which were dexterously used as thermal convertor device to develop photothermal biosensor for exosomes analysis. This work innovatively employed a dual-modality probe of MXenes-BPQDs to establish biosensor, which not only enriched the application of MXenes and BPQDs in biodetection but also provided an effective and reliable method for exosomes detection.

PH-regulated reversible photoluminescence and localized surface plasmon resonances arising from molybdenum oxide quantum dot

Localized surface plasmon resonances (LSPR) and photoluminescence are important for applications of transition-metal oxides. However, simultaneous control of these optical properties is challenging. Here, a facile strategy is presented that simultaneously tunes photoluminescence and visible LSPR of molybdenum oxide quantum dots (MoOx QDs) by controlling lattice vacancies. Specifically, N-doped MoOx QDs were prepared with a one-pot protocol. The introduction of N in MoOx QDs surfaces via ammonia (NH3) not only trapped oxygen molecules in the process of forming MoOx QDs, but also provided enough free electrons to enable tunable optical properties. Thus, a MoOx QD-based dual-modal fluorescence and LSPR assay was demonstrated via lattice vacancy concentration tuning. Upon introduction of H+ or OH−, pH-reversible tunability of the fluorescence and plasmonic resonance was observed. The dual-mode probe was used to detect extreme acidity in bacterial cells. Overall, tunable LSPR and photoluminescence within one nanostructure via pH-regulation should enable multi-modal signal-outputs for sensing platforms and photoelectric nanodevices.

Preparation of AS1411 Aptamer Modified Mn-MoS2 QDs for Targeted MR Imaging and Fluorescence Labelling of Renal Cell Carcinoma.

BackgroundEarly diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma.MethodsIn this work, Mn-MoS2 QDs were synthesized through a simple “bottom-up” one-step hydrothermal method. AS1411 aptamer was modified on the Mn-MoS2 QDs to improve the specificity to renal cell carcinoma. The characteristics of Mn-MoS2 QDs were confirmed by transmission electronic microscopy (TEM), atomic force microscope (AFM), X-ray photoelectron spectrometer (XPS), photoluminescence (PL) emission spectra, etc. Cellular fluorescence labelling was investigated using the Mn-MoS2 QDs and AS1411-Mn-MoS2 QDs. The T1-weighted MR imaging was assessed by the in vitro MR cell imaging and in vivo MR imaging. Finally, the long-term toxicity of Mn-MoS2 QDs was investigated by the hematology and histological analysis.ResultsThe prepared Mn-MoS2 QDs exhibited excellent aqueous property, intense fluorescence, low toxicity, high quantum yield of 41.45% and high T1 relaxivity of 16.95 mM−1s−1. After conjugated with AS1411 aptamer, the AS1411-Mn-MoS2 QDs could specifically fluorescently label the renal carcinoma cells and present a specific MRI signal enhancement in the tumor region of mice bearing renal carcinoma tumors. Furthermore, Mn-MoS2 QDs revealed low toxicity to the mice via hematology and histological analysis.ConclusionThese results demonstrated the potential of AS1411-Mn-MoS2 QD as a novel nanoprobe for targeted MR imaging and fluorescence labelling of renal cell carcinoma.

A dual-mode fluorescent probe for the separate detection of mercury(II) and hydrogen sulfide

A dual-mode fluorescent probe (Probe 1) was developed for the separate detection of Hg2+ and H2S. Probe 1 could detect Hg2+ and H2S through two different reaction sites, with the mechanism of Probe 1 for Hg2+ depending on the desulfurization reaction and for H2S depending on the nucleophilic addition reaction of an aldehyde with H2S. Separate detection of Hg2+ and H2S was achieved by determining the fluorescence emission wavelength of Probe 1-Hg2+ (443 nm, λab = 247 nm) and Probe 1-H2S (504 nm, λab = 256 nm). The fluorescence intensity of Probe 1 has a linear relationship with the concentration of Hg2+ in the range 0–7 μM and the LOD was 39.28 nM. And H2S in the range 0–110 μM, the LOD was 0.7449 μM. With increasing concentrations of Hg2+, test strips gradually became darker in color. The luminescence intensity of test strips gradually increased with increasing H2S concentration, and the initially colorless Probe 1 solution gradually changed to yellow under natural light with increasing H2S concentration. Probe 1 could be used for Hg2+ and H2S detection in real samples.

An Optical/Photoacoustic Dual-Modality Probe: Ratiometric in/ex Vivo Imaging for Stimulated H2S Upregulation in Mice.

Tracking signaling H2S in live mice demands responsive imaging with fine tissue imaging depth and low interferences from tissue scattering/autofluorescence and probe concentration. With complementary advantages of fluorescence and photoacoustic (PA) imaging, optical/PA dual-modality imaging was suggested for in/ex vivo H2S imaging. Therefore, a meso-benzoyloxyltricarboheptamethine cyanine, HS-CyBz, was prepared as the first ratiometric optical/PA dual-modality probe for H2S, profiting from a keto-enol transition sensing mechanism. Tail intravenous injection of this probe leads to probe accumulation in the liver of mice, and the endogenous H2S upregulation triggered by S-adenosyl-l-methionine has been verified by ratiometric optical/PA imaging, suggesting the promising potential of this ratiometric dual-modality imaging.

Small form factor, flexible, dual-modality handheld probe for smartphone-based, point-of-care oral and oropharyngeal cancer screening

.Oral cancer is a growing health issue in low- and middle-income countries due to betel quid, tobacco, and alcohol use and in younger populations of middle- and high-income communities due to the prevalence of human papillomavirus. The described point-of-care, smartphone-based intraoral probe enables autofluorescence imaging and polarized white light imaging in a compact geometry through the use of a USB-connected camera module. The small size and flexible imaging head improves on previous intraoral probe designs and allows imaging the cheek pockets, tonsils, and base of tongue, the areas of greatest risk for both causes of oral cancer. Cloud-based remote specialist and convolutional neural network clinical diagnosis allow for both remote community and home use. The device is characterized and preliminary field-testing data are shared.

A merocyanine-based dual-mode optical probe for detection of hydrazine and its bioimaging application invitro and vivo.

In this paper, a Merocyanine-based turn-on probe (McyA) has been developed for colorimetric and fluorescent dual-mode detection of N2H4 via an intra-molecular charge transfer (ICT) mechanism. In the presence of N2H4, the probe shows an obvious chromogenic response and fluorescent enhancement. Based on this feature, the synthesized McyA can be applied to quantify N2H4 concentration from 0.12 to 5.0 μM and 0.5-10 μM with a detection limit of 0.042 μM (1.3 ppb, S/N = 3) and 0.140 μM (4.5 ppb, S/N = 3), respectively. Moreover, McyA has also be successfully employed for imaging analysis of N2H4 distribution in different organs from the N2H4 ingested mice model, revealing the potential application of McyA as a powerful fluorescent sensor for tracking detection and risk assessment of hydrazine invivo.

Dual-Modal Imaging-Guided Precise Tracking of Bioorthogonally Labeled Mesenchymal Stem Cells in Mouse Brain Stroke.

Noninvasive and precise stem cell tracking after transplantation in living subject is very important to monitor both stem cell destinations and their in vivo fate, which is closely related to their therapeutic efficacy. Herein, we developed bicyclo[6.1.0]nonyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-NPs) as a delivery system of dual-modal stem cell imaging probes. Near-infrared fluorescent (NIRF) dye Cy5.5 was chemically conjugated to the BCN-NPs, and then oleic acid-coated superparamagnetic iron oxide nanoparticles (OA-Fe3O4 NPs) were encapsulated into BCN-NPs, resulting in Cy5.5-labeled and OA-Fe3O4 NP-encapsulated BCN-NPs (BCN-dual-NPs). For bioorthogonal labeling of human adipose-derived mesenchymal stem cells (hMSCs), first, hMSCs were treated with tetra-acetylated N-azidoacetyl-d-mannosamine (Ac4ManNAz) for generating azide (-N3) groups onto their surface via metabolic glycoengineering. Second, azide groups on the cell surface were successfully chemically labeled with BCN-dual-NPs via bioorthogonal click chemistry in vitro. This bioorthogonal labeling of hMSCs could greatly increase the cell labeling efficiency, safety, and imaging sensitivity, compared to only nanoparticle-derived labeling technology. The dual-modal imaging-guided precise tracking of bioorthogonally labeled hMSCs was tested in the photothrombotic stroke mouse model via intraparenchymal injection. Finally, BCN-dual-NPs-labeled hMSCs could be effectively tracked by their migration from the implanted site to the brain stroke lesion using NIRF/T2-weighted magnetic resonance (MR) dual-modal imaging for 14 days. Our observation would provide a potential application of bioorthogonally labeled stem cell imaging in regenerative medicine by providing safety and high labeling efficiency in vitro and in vivo.