Dual-modal Nanoprobe Research Articles

Visualizing dynamic alterations of vitreous viscosity during elevated intraocular pressure in glaucoma with a Near-infrared/Magnetic resonance imaging dual-modal nanoprobe

Glaucoma is a chronic progressive disease leading to irreversible visual impairment and blindness. High intraocular pressure (IOP) resulting from abnormally high outflow resistance is a major risk factor for glaucoma development, however, it is unclear how IOP elevation influences the structure and function of the retina and the optic nerve via vitreous humor located between the lens and retina in the eye. To understand vitreous biomechanical and stimulus response toward IOP elevation, we developed a novel near-infrared (NIR)/MRI dual-modal nanoprobe, DTA/P-NCA/17F@Co, which is composed of N, N-dimethyl-4(thien-2-yl)-aniline group (DTA) as NIR fluorophore and the fluorine-based polyamino acid cobalt nanoparticles (P-NCA/17F@Co) as T2 contrast agent. These nanoprobes exhibit good biocompatibility, low surface energy characteristics, and viscosity-responsive NIR emission and T2 relaxation values. The intrinsic viscosity-sensitivemechanismof nanoprobes was ascribed to constrained molecular motion in high-viscosity vitreous chamber, which causes enhanced fluorescence emission and shortened T2 relaxation times. By using its ability for dual-modal visualization of viscosity, we achieved non-invasive in vivo monitoring the changes in vitreous viscosity during elevated IOP in a glaucoma rat model. In vivo experiments validated that vitreous viscosity is very strongly correlated with IOP elevation induced by glaucoma, much earlier than structural and functional change in the retina. Our findings revealed that IOP elevation induced the increase of vitreous viscosity, indicating that monitoring vitreous viscosity is key to the glaucoma model. This study not only provides versatile nanoprobes for dual-modal visualization of biomechanical properties of the vitreous humor in its native environment, but also shows great potential in the early diagnosis of glaucoma.

Development of in vitro and in vivo c-Met targeted dual-modal nanoprobes for NIR II fluorescent bioimaging and magnetic resonance imaging of breast carcinoma metastasis

Because of the conventional bioimaging methods, including ultrasound and X-ray examinations often lack accuracy and sensitivity in the early diagnosis, as a heterogeneous subtype of breast cancer, it remains an urgent need to develop efficaciously and sensitively diagnostic drivers of triple negative breast cancer (TNBC). The overexpression of c-mesenchymal epithelial transition-factor (c-Met) is associated with the basal subtype of breast carcinoma and linked with decreased survival rate of TNBC patients. Here, we have synthesized a dual-modal nanoprobe with luminescence imaging in the bio-window of near infrared II region (NIR II, 1000–1700) and magnetic resonance imaging (MRI) performances. After c-Met targeting binding protein decoration, this Fe3O4@mSiO2-ICG/cMBP had outstanding size stability and preeminent biocompatibility. Meaningfully, it presented effective TNBC cells recognition in vitro. Besides, after caudal-vein injection of this nanoprobe, both NIR II luminescence imaging and MRI demonstrated that it can more efficiently concentrated in metastatic TNBC tumors in comparison with Fe3O4@mSiO2-ICG and clinical used Gd-DTPA. Meanwhile, the core–shell nanoprobes also showed negligible toxicity in vivo. All results suggested that our cMBP modified nanocomposite could provide a fascinating and efficient non-invasive diagnostic tool for TNBC detection in clinic.

Dual-mode nanoprobe strategy integrating ultrasound and near-infrared light for targeted and synergistic arterial thrombolysis

Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis.Graphical

Gadolinium-doped carbon dots with long-wavelength emission for dual-modal imaging

Subject of study. This study is focused on luminescent carbon dots derived from o-phenylenediamine and gadolinium chloride or nitrate hexahydrate. Aim of study. The study aims to fabricate long-wavelength photoluminescent gadolinium-doped carbon dots that could function as contrast agents for magnetic resonance imaging. Additionally, the study investigates the impact of the precursor type used on the chemical composition and optical transitions of the resulting nanoparticles. Method. Carbon dots were synthesized using a one-step solvothermal method, and their composition and optical properties were analyzed using spectroscopy methods. Magnetic resonance imaging was conducted using a clinical magnetic resonance imaging scanner with a field strength of 1.5 T. Main results. In this study, two types of carbon dots were synthesized from o-phenylenediamine and gadolinium chloride or nitrate hexahydrate using the solvothermal method. Metal doping, at a concentration sufficient for further investigations, is achieved only when gadolinium chloride is used. Additionally, the presence of gadolinium chloride during the synthesis leads to the formation of luminescent centers within the carbon dots with emission at 600–720 nm and a photoluminescence quantum yield of 6.3%. In contrast, gadolinium nitrate increases the nitrogen content within the o-phenylenediamine-based carbon dots while inhibiting metal doping. The luminescent band with an emission maximum at 550 nm and a photoluminescence quantum yield of 7.4% originates from the o-phenylenediamine derivatives formed within such carbon dots. The study results also show that the gadolinium-doped carbon dots alter the relaxation times during magnetic resonance scanning, and the calculated relaxivity (r1 and r2) values are 6.4 and 38.6L⋅mmol−1⋅s−1, respectively. Thus, the synthesized carbon dots function as positive contrast agents during magnetic resonance scanning. Practical significance. Carbon dots with long-wavelength emission are promising nanoprobes for luminescence imaging. With gadolinium doping, these nanoparticles can also be used as contrast agents during magnetic resonance imaging. Consequently, carbon dots based on o-phenylenediamine and gadolinium chloride hexahydrate can be further utilized as dual-mode nanoprobes for bioimaging.

Luciferase-Decorated Gold Nanorods as Dual-Modal Contrast Agents for Tumor-Targeted High-Performance Bioluminescence/Photoacoustic Imaging.

Gold nanorods (AuNRs) have been considered highly compelling materials for early cancer diagnosis and have aroused a burgeoning fascination among the biomedical sectors. By leveraging the versatile tunable optical properties of AuNRs, herein, we have developed a novel tumor-targeted dual-modal nanoprobe (FFA) that exhibits excellent bioluminescence and photoacoustic imaging performance for early tumor diagnosis. FFA has been synthesized by anchoring the recombinant bioluminescent firefly luciferase protein (Fluc) on the folate-conjugated AuNRs via the PEG linker. TEM images and UV-vis studies confirm the nanorod morphology and successful conjugation of the biomolecules to AuNRs. The nanoprobe FFA relies on the ability of the folate module to target the folate receptor-positive tumor cells actively, and simultaneously, the Fluc module facilitates excellent bioluminescent properties in physiological conditions. The success of chemical engineering in the present study enables stronger bioluminescent signals in the folate receptor-positive cells (Skov3, Hela, and MCF-7) than in folate receptor-negative cells (A549, 293T, MCF-10A, and HepG2). Additionally, the AuNRs induced strong photoacoustic conversion performance, enhancing the resolution of tumor imaging. No apparent toxicity was detected at the cellular and mouse tissue levels, manifesting the biocompatibility nature of the nanoprobe. Prompted by the positive merits of FFA, the in vivo animal studies were performed, and a notable enhancement was observed in the bioluminescent/photoacoustic intensity of the nanoprobe in the tumor region compared to that in the folate-blocking region. Therefore, this synergistic dual-modal bioluminescent and photoacoustic imaging platform holds great potential as a tumor-targeted contrast agent for early tumor diagnosis with high-performance imaging information.

Surface-enhanced Raman scattering-fluorescence dual-mode probes for target imaging of tumors, organoids and cancerous cells

A dual-mode nanoprobe (DMNP) overcomes the limitations of single probes and offers superior performance by combining their advantages. Herein, we report a DMNP design that features a gold nanosphere core and two layers of silica wrapping. The gold core surface is coated with 4-mercaptobenzoic acid(4-MBA), which serves as a Raman reporter. After the initial silica encapsulation, fluorophores in the form of conjugated polymer nanoparticles (CPNs) are applied to the surface. Finally, the encapsulation process is completed by adding the second layer of silica. The probe has dual-mode capabilities, including surface-enhanced Raman scattering (SERS) with a Raman enhancement factor of 134.1, and metal-enhanced fluorescence (MEF) with a fluorescence enhancement factor of 1.42. When modified with glycoprotein-3 (GPC3) antibody, the DMNPs probe shows excellent performance in fluorescence and SERS imaging for HepG2 liver cancer cells. When DMNP is conjugated with the breast tumor-specific antibody CA153, the DMNPs-AbCA153 probe enables imaging and induces apoptosis of breast cancer cells. These probes can serve as a platform for visualizing the distribution of cancer cell surface markers by modifying antibodies to recognize the cell surface. They have also shown significant potential as probes for oncology diagnosis and treatment monitoring.

Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging

BackgroundThe general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape.ResultsIn this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments.ConclusionsWe believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.Graphical

Lanthanide-grafted covalent organic framework as a colorimetric and luminescence dual-mode nanoprobe for tetracycline detection

Tetracyclines (TCs) are a group of antibiotics commonly using for infection treatment, however, the leftovers in potable water and food which are derived from the abuse of TCs lead to the adverse human health and environmental impacts. Herein, we developed a lanthanide-grafted covalent organic framework (COF) as a colorimetric and luminescence dual-mode nanoprobe to realize precise, sensitive, rapid, real-time TC determination. Ce3+, Eu3+ ions were chosen to functionalize COFs due to their particular corresponding catalytic and luminescent characteristic for bimodal sensing. COF-Ce-Eu can work as an enzyme mimic to catalytically oxidize the substrate of 3,3′,5,5′-tetramethylbenzidine (TMB) with existence of H2O2, besides, the addition of TC is conducive to promote the pristine catalytic activity as the formation of complexation of COF-Ce-Eu with TC. The catalytic activity and the absorbance of COF-Ce-Eu directly correlate to TC concentration. The ratiometric luminescence response was established on the intensity ratio of the broad band centered at 512 nm originated from the matrix COF and the sharp peak at 616 nm originated from Eu3+. The decrease in luminescence intensity of the peak at 512 nm and the increase at 616 nm depended on TC concentration. This colorimetric and luminescence dual-mode platform exhibits excellent selectivity and sensitivity towards TC, with a wide linear range of 0–50 μM, and low detection limits of 24 nM and 3.4 nM, respectively. The designed bimodal sensing strategy provide a promising double assurance for the accurate trace of TC in food and water samples.

Analyte-perturbed balance between reducibility and fluorescence of Ti3C2 MXene quantum dots for label-free, dual-mode detection of silver ions

BackgroundAs an emerging and attractive low-dimensional functional materials, Ti3C2 MXene quantum dots (QDs) enlarge the toolbox of fluorescence sensing. However, monochromatic fluorescence, which only provide one single signal, is often beset by challenges such as false-positive readouts and limitations in selectivity. Consequently, to improve the sensing accuracy by means of cross-verified dual-signal authentication, the endeavor to engineer dual-mode nanoprobes based on Ti3C2 QDs, incorporating both the capability of fluorescence and an alternative sensing mechanism, emerges as a compelling avenue. ResultsHere, based on the alterations in colorimetric and fluorescent signals of Ti3C2 QDs with the addition of Ag+, we propose a dual-mode sensor obviating the necessity for nanoprobe labeling. Owing to the decent reducibility of Ti3C2 QDs, Ag+ is adsorbed and reduced, resulting in the generation of plasmonic Ag nanoparticles (NPs), which simultaneously trigger colorimetric responses of the solution and enhance the fluorescent emission of Ti3C2 QDs. The confluence of colorimetry and fluorometry within this strategy optimally harnesses the modulating role of the acquired Ag NPs on the reducing capability and fluorescence characteristics of Ti3C2 QDs. The equilibrium imparts versatility and promising prospects to this analyte-triggered label-free method, which enables a remarkable specificity and an excellent detecting limit (0.45 μM) for Ag+. SignificanceThe balance between reducibility and fluorescence of Ti3C2 QDs for dual-mode detection is inventively demonstrated. With the exemplification of a direct influence of both features of the nanoprobe via the introduction of analytes, this study opens the feasibility of the analyte-perturbed felicitous equilibrium, which endows label-free methods with versatility and promising prospects. This design may evoke more biosensing strategies with the function of double-signal mutual verification.

Lighting up endogenous H2O2 in the tumor microenvironment using a dual-mode nanoprobe for long afterglow and MR bioimaging.

Persistent luminescent nanoparticles (PLNPs) are excellent luminescent materials, and near-infrared PLNPs are efficiently applied for biosensing and bioimaging due to their advantages of no excitation, excellent light stability and long afterglow. However, due to interference from the complex environment within organisms, single-mode imaging methods often face limitations in selectivity, sensitivity, and accuracy. Therefore, it is desirable to construct a dual-mode imaging probe strategy with higher specificity and sensitivity for bioimaging. Magnetic resonance imaging (MRI) has been widely used in the field of bioimaging due to its advantages of high resolution, non-radiation and non-invasiveness. Here, by combining near-infrared PLNPs and manganese dioxide (MnO2) nanosheets, a sensitive and convenient dual-mode "turn on" bioimaging nanoprobe ZGC@MnO2 has been developed for long afterglow imaging and MRI of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment (TME). The monitoring of H2O2 has garnered significant attention due to its crucial role in human pathologies. For the dual-mode "turn on" bioimaging nanoprobe, the near-infrared PLNPs of quasi-spherical ZnGa2O4:Cr (ZGC) nanoparticles were synthesized as luminophores, and MnO2 nanosheets were utilized as a fluorescence quencher, carrier and H2O2 recognizer. H2O2 in the TME could reduce MnO2 nanosheets to Mn2+ for MRI, and ZGC nanoparticles were released for long afterglow imaging. Finally, the ZGC@MnO2 nanoprobe exhibited a rapid response, an excellent signal-to-noise ratio and a limit of detection of 3.67 nM for endogenous H2O2 in the TME. This dual-mode approach enhances the detection sensitivity for endogenous H2O2, thereby facilitating the research of endogenous H2O2-associated diseases and clinical diagnostics.

Dual-Mode Nanoprobes Based on Lanthanide Doped Fluoride Nanoparticles Functionalized by Aryl Diazonium Salts for Fluorescence and SERS Bioimaging.

The design of dual-mode fluorescence and Raman tags stimulates a growing interest in biomedical imaging and sensing applications as they offer the possibility to synergistically combine the versatility and velocity of fluorescence imaging with the specificity of Raman spectroscopy. Although lanthanide-doped fluoride nanoparticles (NPs) are among the most studied fluorescent nanoprobes, their use for the development of bimodal fluorescent-Raman probes has never been reported yet, to the best of the authors knowledge, probably due to the difficulty to functionalize them with Raman reporter groups. This gap is filled herein by proposing a fast and straightforward approach based on aryl diazonium salt chemistry to functionalize Eu3+ or Tb3+ doped CaF2 and LaF3 NPs by Raman scatters. The resulting surface-enhanced Raman spectroscopy (SERS)-encoded lanthanide-doped fluoride NPs retain their fluorescence labeling capacity and display efficient SERS activity for cell bioimaging. The potential of this new generation of bimodal nanoprobes is assessed through cell viability assays and intracellular fluorescence and Raman imaging, opening up unprecedented opportunities for biomedical applications.

Dual-Mode Gold Nanocluster-Based Nanoprobe Platform for Two-Photon Fluorescence Imaging and Fluorescence Lifetime Imaging of Intracellular Endogenous miRNA.

Bioimaging is widely used in various fields of modern medicine. Fluorescence imaging has the advantages of high sensitivity, high selectivity, noninvasiveness, in situ imaging, and so on. However, one-photon (OP) fluorescence imaging has problems, such as low tissue penetration depth and low spatiotemporal resolution. These disadvantages can be solved by two-photon (TP) fluorescence imaging. However, TP imaging still uses fluorescence intensity as a signal. The complexity of organisms will inevitably affect the change of fluorescence intensity, cause false-positive signals, and affect the accuracy of the results obtained. Fluorescence lifetime imaging (FLIM) is different from other kinds of fluorescence imaging, which is an intrinsic property of the material and independent of the material concentration and fluorescence intensity. FLIM can effectively avoid the fluctuation of TP imaging based on fluorescence intensity and the interference of autofluorescence. Therefore, based on silica-coated gold nanoclusters (AuNCs@SiO2) combined with nucleic acid probes, the dual-mode nanoprobe platform was constructed for TP and FLIM imaging of intracellular endogenous miRNA-21 for the first time. First, the dual-mode nanoprobe used a dual fluorescence quencher of BHQ2 and graphene oxide (GO), which has a high signal-to-noise ratio and anti-interference. Second, the dual-mode nanoprobe can detect miR-21 with high sensitivity and selectivity in vitro, with a detection limit of 0.91 nM. Finally, the dual-mode nanoprobes performed satisfactory TP fluorescence imaging (330.0 μm penetration depth) and FLIM (τave = 50.0 ns) of endogenous miR-21 in living cells and tissues. The dual-mode platforms have promising applications in miRNA-based early detection and therapy and hold much promise for improving clinical efficacy.

Heteroatom-Doped Carbon Quantum Dots and Polymer Composite as Dual-Mode Nanoprobe for Fluorometric and Colorimetric Determination of Picric Acid.

Oxygen- and nitrogen-heteroatom-doped, water-dispersible, and bright blue-fluorescent carbon dots (ON-CDs) were prepared for the selective and sensitive determination of 2,4,6-trinitrophenol (picric acid, PA). ON-CDs with 49.7% quantum yield were one-pot manufactured by the reflux method using citric acid, d-glucose, and ethylenediamine precursors. The surface morphology of ON-CDs was determined by scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering, Raman, infrared, and X-ray photoelectron spectroscopy techniques, and their photophysical properties were estimated by fluorescence spectroscopy, UV-vis spectroscopy, fluorescence lifetime measurement, and 3D-fluorescence excitation-emission matrix analysis. ON-CDs at an average particle size of 3.0 nm had excitation/emission wavelengths of 355 and 455 nm, respectively. With the dominant inner-filter effect- and hydrogen-bonding interaction-based static fluorescence quenching phenomena supported by ground-state charge-transfer complexation (CTC), the fluorescence of ON-CDs was selectively quenched with PA in the presence of various types of explosives (i.e., 2,4,6-trinitrotoluene, tetryl, 1,3,5-trinitroperhydro-1,3,5-triazine, 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane, pentaerythritol tetranitrate, 3-nitro-1,2,4-triazole-5-one, and TATP-hydrolyzed H2O2). The analytical results showed that the emission intensity varied linearly with a correlation coefficient of 0.9987 over a PA concentration range from 1.0 × 10-9 to 11.0 × 10-9 M. As a result of ground-state interaction (H-bonding and CTC) of ON-CDs with PA, an orange-colored complex was formed different from the characteristic yellow color of PA in an aqueous medium, allowing naked-eye detection of PA. The detection limits for PA with ON-CDs were 12.5 × 10-12 M (12.5 pM) by emission measurement and 9.0 × 10-10 M (0.9 nM) by absorption measurement. In the presence of synthetic explosive mixtures, common soil cations/anions, and camouflage materials, PA was recovered in the range of 95.2 and 102.5%. The developed method was statistically validated against a reference liquid chromatography coupled to tandem mass spectrometry method applied to PA-contaminated soil. In addition, a poly(vinyl alcohol)-based polymer composite film {PF(ON-CDs)} was prepared by incorporating ON-CDs, enabling the smartphone-assisted fluorometric detection of PA.

A dual-mode nanoprobe based on silicon nanoparticles and Fe(II)-phenanthroline for the colorimetric and fluorescence determination of nitrite

A dual-mode nanoprobe based on silicon nanoparticles and Fe(II)-phenanthroline for the colorimetric and fluorescence determination of nitrite

A Smart Responsive Fluorescence-MR Nanoprobe for Monitoring Tumor Response to Immunotherapy.

Accurately evaluating tumor responses to immunotherapyis clinically relevant. However, non-invasive, real-time visualization techniques to evaluate tumor immunotherapy are still lacking. Herein, a smart responsive fluorescence-MR dual-modal nanoprobe, QM(GP)-MZF(CP), is reported that can be targeted for cleavage by the cytotoxic T cell activation marker granzyme B and the apoptosis-related marker cysteine-aspartic acid-specific protease 3 (Caspase-3). The probe uses quinoline-malononitrile (QM), an aggregation-induced emission luminogen, and Mn-Zn ferrite magnetic nanoparticles (MZF-MNPs), a T2-weighted imaging (T2WI) contrast agent, as imaging molecules that are linked with the substrate peptides specific to granzyme B and Caspase-3. Therefore, both granzyme B and Caspase-3 can target and cleave the substrate peptides in QM(GP)-MZF(CP). Via aggregation-induced fluorescence imaging of QM and the aggregation-induced T2WI-enhanced imaging effect of MZF-MNPs, the status of T cells after tumor immunotherapy and the subsequent triggering of tumor cell apoptosis can be determined to identify tumor responsiveness to immunotherapy and thereby evaluate the effectiveness of this therapy in the early stages of treatment.

Dual-mode nanoprobe for selective detection of arsenite based on yellow fluorescent carbon dots

Arsenic is a toxic heavy metal element and widely distributed in nature, however, long-term exposure to low doses of arsenite (As3+) is harmful to human health. Therefore, it is particularly important to establish a quick and sensitive detection method for As3+ in the environment. Yellow fluorescent carbon dots were prepared by hydrothermal method with rhodamine B and citrate as precursors. The RbB-CDs were purified by thin layer chromatography and chromatographic column. The good line ranges of 0–5 μg/L and 10–50 μg/L As3+ were obtained with low detection limits of 0.75 μg/L and 5.00 μg/L based on fluorescence, respectively, while a good line range of 0–50 μg/L was obtained with a low detection limit of 3.03 μg/L based on UV absorbance. Furthermore, static quenching was verified to work in the quenching process of As3+ towards RbB-CDs fluorescence. In addition, the yellow fluorescent nanoprobe was employed to determine the As3+ content in tap water, lake water, and river water samples. It showed good potential to detect As3+ in the environment.

SERS-fluorescence dual-mode nanoprobe for the detection and imaging of Bax mRNA during apoptosis.

Adual-mode nanoprobe was constructed to detect Bax messenger RNA (mRNA), consisting of gold nanotriangles (AuNTs), a Cy5-modified recognition sequence, and a thiol-modified DNA sequence. Bax mRNA is one of the key pro-apoptotic factors in the apoptosis pathway. Raman enhancement and fluorescence quenching of the signal group Cy5 were performed using AuNTs as substrates. The thiol-modified nucleic acid chain is partially complementary to the Cy5-modified nucleic acid chain to form a double strand and is linked to the AuNTs by the Au-S bond. When Bax mRNA is present, the Cy5-modified strand specifically binds to it to form a more stable duplex, making Cy5 far away from AuNTs, and SERS signal is weakened while fluorescence signal is enhanced. The nanoprobe can be used for the quantitative detection of Bax mRNA in vitro. Combined with the high sensitivity of SERS and the visualization of fluorescence, this method has good specificity and can be used for in situ imaging and dynamic monitoring of Bax mRNA during deoxynivalenol (DON) toxin-induced apoptosis of HepG2 cells. DON plays a pathogenic role mainly by inducing cell apoptosis. Theresults confirmed that the proposed dual-mode nanoprobe has good versatility in various human cell lines.

A SERS/fluorescence dual-mode immuno-nanoprobe for investigating two anti-diabetic drugs on EGFR expressions.

A surface-enhanced Raman scattering (SERS)/fluorescence dual-mode nanoprobe was proposed to assess anti-diabetic drug actions from the expression level of the epidermal growth factor receptor (EGFR), which is a significant biomarker of breast cancers. The nanoprobe has a raspberry shape, prepared by coating a dye-doped silica nanosphere with a mass of SERS tags, which gives high gains in fluorescence imaging and SERS measurement. The in situ detection of EGFR on the cell membrane surfaces after drug actions was achieved by using this nanoprobe, and the detection results agree with the enzyme-linked immunosorbent assay (ELISA) kit. Our study suggests that rosiglitazone hydrochloride (RH) may be a potential drug for diabetic patients with breast cancer, while the anti-cancer effect of metformin hydrochloride (MH) is debatable since MH slightly promotes the EGFR expression of MCF-7 cells in this study. This sensing platform endows more feasibility for highly sensitive and accurate feedback of pesticide effects at the membrane protein level.

A ratiometric near-infrared fluorescence/photoacoustic dual-modal probe with strong donor dithienopyrrole for in vivo nitric oxide detection

Integrating the imaging techniques of near-infrared fluorescence (NIRF) and photoacoustic (PA) can make up for each other and provide more useful medical information. Ratiometric imaging activated by disease-associated biomarkers can further augment imaging specificity. However, very few studies have employed the NIRF/PA dual-modal ratiometric imaging to improve the accuracy and specificity of disease diagnosis to date. In this paper, we present the synthesis of a nitric oxide (NO)-activated ratiometric NIRF/PA dual-modal nanoprobe RAPNP for in vivo NO imaging. The ratiometric imaging function was achieved jointly by a NO/acidity-responsive molecule DTP-BTDA and a nonresponsive fluorophore DTP-BBTD. In these fluorophores, the dithienopyrrole (DTP) moiety had strong electron-donating ability and imparted strong intramolecular charge transfer and relatively long emission wavelengths. The BTDA moiety in DTP-BTDA could be rapidly oxidized by NO under weak acidic environments, achieving the NIRF and PA signal activation. By using RAPNP as a contrast agent, we achieved the ratiometric detection of the endogenous NO in inflammatory bowel disease by NIRF/PA dual-modal imaging. This work provides the first case of the NIRF/PA dual-signal ratiometric probe for the real-time detection of NO in vivo.

A clinically translatable kit for MRI/NMI dual-modality nanoprobes based on anchoring group-mediated radiolabeling.

Magnetic resonance imaging (MRI)/nuclear medicine imaging (NMI) dual-modality imaging based on radiolabeled nanoparticles has been increasingly exploited for accurate diagnosis of tumor and cardiovascular diseases by virtue of high spatial resolution and high sensitivity. However, significant challenges exist in pursuing truly clinical applications, including massive preparation and rapid radiolabeling of nanoparticles. Herein, we report a clinically translatable kit for the convenient construction of MRI/NMI nanoprobes relying on the flow-synthesis and anchoring group-mediated radiolabeling (LAGMERAL) of iron oxide nanoparticles. First, homogeneous iron oxide nanoparticles with excellent performance were successfully obtained on a large scale by flow synthesis, followed by the surface anchoring of diphosphonate-polyethylene glycol (DP-PEG) to simultaneously render the underlying nanoparticles biocompatible and competent in robust labeling of radioactive metal ions. Moreover, to enable convenient and safe usage in clinics, the DP-PEG modified nanoparticle solution was freeze-dried and sterilized to make a radiolabeling kit followed by careful evaluations of its in vitro and in vivo performance and applicability. The results showed that 99mTc labeled nanoprobes are effectively obtained with a labeling yield of over 95% in 30 minutes after simply injecting Na[99mTcO4] solution into the kit. In addition, the Fe3O4 nanoparticles sealed in the kit can well stand long-term storage even for 300 days without deteriorating the colloidal stability and radiolabeling yield. Upon intravenous injection of the as-prepared radiolabeled nanoprobes, high-resolution vascular images of mice were obtained by vascular SPECT imaging and magnetic resonance angiography, demonstrating the promising clinical translational value of our radiolabeling kit.