Dual-mode Fluorescence Research Articles

Dual-mode fluorescence biosensor platform based on T-shaped duplex structure for detection of microRNA and folate receptor

In this work, a microfluidic paper-based fluorescent sensor device was constructed for quantitative detection of microRNA (miRNA) and determination of the expression of folate receptor (FR) on the cell surface. It is worth pointing out that simultaneous detection of two biomarkers in cancer was achieved through dynamic self-assembly of T-shaped duplex structure. T-shaped duplex structure can respond to specific triggers and convert to an output due to the conformation changes, it is meaningful to fabricate T-shaped duplex structure into powerful biosensors that can monitor chemical stimuli. Moreover, lamellar MnO2 nanosheets were synthesized, which exhibited excellent quenching ability via adsorbed fluorophore-labeled ssDNA, but the adsorption of the dsDNA was significantly lower than ssDNA because of the shielding of nucleobase pairs by the phosphate groups. This newly designed biosensor provided a sensitive detection of miR-21 from 0.01 to 5.0 fM with a relatively low detection limit of 0.0033 fM. Besides, the present sensing system has a detection of FR in the range from 2.0 to 30.0 ng/mL with the detection limit of 0.667 ng/mL. As biological markers for disease diagnosis, the detection of FR and miRNA will provide a new approach and therapeutic tool for early clinical diagnosis.

Preliminary Study of MR and Fluorescence Dual-mode Imaging: Combined Macrophage-Targeted and Superparamagnetic Polymeric Micelles.

Purpose: To establish small-sized superparamagnetic polymeric micelles for magnetic resonance and fluorescent dual-modal imaging, we investigated the feasibility of MR imaging (MRI) and macrophage-targeted in vitro.Methods: A new class of superparamagnetic iron oxide nanoparticles (SPIONs) and Nile red-co-loaded mPEG-Lys3-CA4-NR/SPION polymeric micelles was synthesized to label Raw264.7 cells. The physical characteristics of the polymeric micelles were assessed, the T2 relaxation rate was calculated, and the effect of labeling on the cell viability and cytotoxicity was also determined in vitro. In addition, further evaluation of the application potential of the micelles was conducted via in vitro MRI.Results: The diameter of the mPEG-Lys3-CA4-NR/SPION polymeric micelles was 33.8 ± 5.8 nm on average. Compared with the hydrophilic SPIO, mPEG-Lys3-CA4-NR/SPION micelles increased transversely (r2), leading to a notably high r2 from 1.908 µg/mL-1S-1 up to 5.032 µg/mL-1S-1, making the mPEG-Lys3-CA4-NR/SPION micelles a highly sensitive MRI T2 contrast agent, as further demonstrated by in vitro MRI. The results of Confocal Laser Scanning Microscopy (CLSM) and Prussian blue staining of Raw264.7 after incubation with micelle-containing medium indicated that the cellular uptake efficiency is high.Conclusion: We successfully synthesized dual-modal MR and fluorescence imaging mPEG-Lys3-CA4-NR/SPION polymeric micelles with an ultra-small size and high MRI sensitivity, which were effectively and quickly uptaken into Raw 264.7 cells. mPEG-Lys3-CA4-NR/SPION polymeric micelles might become a new MR lymphography contrast agent, with high effectiveness and high MRI sensitivity.

Magnetofluorescent Carbon Quantum Dot Decorated Multiwalled Carbon Nanotubes for Dual-Modal Targeted Imaging in Chemo-Photothermal Synergistic Therapy.

Magnetofluorescent nanoparticles with diagnostic and therapeutic functions show great promise in nanomedicine. Here, we report the magnetofluorescent carbon nanotubes (CNTs)/doxorubicin (DOX) nanocomposites and their functions act in synergetic chemo-photothermal synergistic therapy (Chemo/PTT) in cancer excision. Magnetofluorescent CNTs conjugated with a folic acid (FA-GdN@CQDs-MWCNTs) were targets for dual-modal fluorescence (FL)/magnetic resonance (MR) imaging. Experiments in vitro and in vivo identified FA-GdN@CQDs-MWCNTs with low toxicity, and good biocompatibility. Moreover, FA-GdN@CQDs-MWCNTs whose release can be fostered by pH and NIR light dual-stimuli had been proved to be available for loading DOX. Following nuclear translocations, FA-GdN@CQDs-MWCNTs were engineered to deliver DOX that targeted the nuclei. In vivo experiment indicates that the Chemo/PTT, as compared with the respective single treatment, can significantly control tumor growth. In addition, Chemo/PTT was not shown to render any appreciable toxicity. These findings suggest that the FA-GdN@CQDs-MWCNTs/DOX could function as a multifunctional platform for simultaneous FL/MR imaging, PTT therapy, and drug delivery.

In Vivo Dual-Modality Fluorescence and Magnetic Resonance Imaging-Guided Lymph Node Mapping with Good Biocompatibility Manganese Oxide Nanoparticles.

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T1 contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy7.5), which functions as a fluorescence imaging (FI) agent as well as a magnetic resonance imaging (MRI) imaging agent. The formed Mn3O4@PEG-Cy7.5 NPs with the size of ~10 nm exhibit good colloidal stability in different physiological media. Serial FI and MRI studies that non-invasively assessed the bio-distribution pattern and the feasibility for in vivo dual-modality imaging-guided lymph node mapping have been investigated. In addition, histological and biochemical analyses exhibited low toxicity even at a dose of 20 mg/kg in vivo. Since Mn3O4@PEG-Cy7.5 NPs exhibited desirable properties as imaging agents and good biocompatibility, this work offers a robust, safe, and accurate diagnostic platform based on manganese oxide NPs for tumor metastasis diagnosis.

Facile one-pot synthesis of hollow mesoporous fluorescent Gd2O3:Eu/calcium phosphate nanospheres for simultaneous dual-modal imaging and pH-responsive drug delivery

The hollow nanospheres (NSs) composed of lanthanides have become a hot topic owing to their uncommon magnetic and optical properties arising from the 4f electrons. However, only a few novel methods have been developed for effectively integrating small calcium phosphate (CaP) nanoparticles and rare earth oxide drug carriers into an individual hollow mesoporous nanosphere. Herein, we report a facile, reproducible, room-temperature solution method to prepare multifunctional fluorescent hollow mesoporous Gd2O3:Eu/CaP (designated as HM-Gd2O3:Eu/CaP) NSs by using polyacrylic acid calcium (PAA-Ca) as a template. The excellent luminescent property and obvious T1-enhancement effect as well as the HM structure endow the HM-Gd2O3:Eu/CaP NSs with the capacity of simultaneous dual-modal fluorescence, magnetic resonance (MR) imaging and drug delivery. The nanocontainer-functionality of the HM-Gd2O3:Eu/CaP NSs is further validated upon filling with the anti-cancerogenic agent doxorubicin (drug-loading capacity is 749 μg mg−1). In addition, the HM-Gd2O3:Eu/CaP NSs display excellent pH-responsive and sustained drug release property. In vitro cell cytotoxicity tests verify the HM-Gd2O3:Eu/CaP NSs have good biocompatibility when the concentration ≤25 mg mL−1. Taken together, the results suggested that the HM-Gd2O3:Eu/CaP NSs can be applied as fluorescence and MR dual-modal imaging contrast agents and drug delivery vehicles.

Spectroscopic study on the interaction of organic-inorganic hybrid perovskite nanoparticles with linear aliphatic alcohols

In this work, we studied the interactions between organic-inorganic hybrid perovskite and polar aliphatic alcohols based on the absorption and photoluminescence changes of highly fluorescent CH3NH3PbBr3 perovskite nanoparticles. Perovskite film gradually lost its yellow color and intense green emission in response to the aliphatic alcohol solvents. From the kinetic study of UV/Vis absorption changes and X-ray diffraction analysis, it was observed that optical properties of perovskite nanoparticles were linearly quenched by a polarity increase of aliphatic alcohols, concomitant with a conversion of crystalline structure. These results provide the insight into the origin of intrinsic instability of perovskites by polar molecules. Furthermore, sensitive response of perovskite nanoparticles to the polar molecules suggests a new practical strategy for colorimetric and fluorescent dual mode sensing of the molecule's polarity.

From Detection to Resection: Photoacoustic Tomography and Surgery Guidance with Indocyanine Green Loaded Gold Nanorod@liposome Core-Shell Nanoparticles in Liver Cancer.

Conventional imaging methods encounter challenges in diagnosing liver cancer that is less than 10 mm or without typical hypervascular features. With deep penetration and high spatial resolution imaging capability, the emerging photoacoustic tomography may offer better diagnostic efficacy for noninvasive liver cancer detection. Moreover, near-infrared fluorescence imaging-guided hepatectomy was proven to be able to identify nodules at the millimeter level. Thus, suitable photoacoustic and fluorescence dual-modality imaging probe may benefit patients in early diagnosis and complete resection. In this study, we fabricated indocyanine green loaded gold nanorod@liposome core-shell nanoparticles (Au@liposome-ICG) to integrate both imaging strategies. These nanoparticles exhibit superior biocompatibility, high stability, and enhanced dual-model imaging signals. Next, we explored their effectiveness of tumor detection and surgery guidance in orthotopic liver cancer mouse models. Histological analysis confirmed the accuracy of the probe in liver cancer detection and resection. This novel dual-modality nanoprobe holds promise for early diagnosis and better surgical outcome of liver cancer and has great potential for clinical translation.

Red Emission B, N, S-co-Doped Carbon Dots for Colorimetric and Fluorescent Dual Mode Detection of Fe3+ Ions in Complex Biological Fluids and Living Cells.

Colorimetric and fluorescent dual mode detection methods have gained much attention in recent years; however, it is still desirable to develop new colorimetric and fluorescent dual mode nanosensors with more simple preparation procedures, low cost, and excellent biocompatibility. Herein, a colorimetric and fluorescent nanosensor based on B, N, S-co-doped carbon dots (BNS-CDs) was synthesized by one-step hydrothermal treatment of 2,5-diaminobenzenesulfonic acid and 4-aminophenylboronic acid hydrochloride. Using this nanosensor, a highly sensitive assay of Fe3+ in the range of 0.3-546 μM with a detection limit of 90 nM was provided by quenching the red emission fluorescence. It is more attractive that Fe3+ can also be visualized by this nanosensor via evident color changes of the solution (from red to blue) under sunlight without the aid of an ultraviolet (UV) lamp. Furthermore, the designed nanosensor can be applied for efficient detection of intracellular Fe3+ with excellent biocompatibility and cellular imaging capability, and it holds great promise in biomedical applications.

Core-interlayer-shell Fe3O4@mSiO2@lipid-PEG-methotrexate nanoparticle for multimodal imaging and multistage targeted chemo-photodynamic therapy

Multimodal imaging-guided multistage targeted synergistic combination therapy possesses many advantages including increased tumoricidal effect, reduced toxicity, and retarded drug resistance. Herein, we have elaborately developed a core-interlayer-shell structure Fe3O4@mSiO2@lipid-PEG-methotrexatenanoparticle(FMLM), in which the Fe3O4 core could be used for magnet-stimulate-response drug release, magnetic resonance imaging, and early-phase magnet targeting ability; the mSiO2 layer could encapsulate anticancer drug doxorubicin (Dox) for chemotherapy; and the protective shell of lipid-PEG and lipid-PEG-methotrexate offered later-phase specific cellular targeting ability, good water dispersibility, and loading of photosensitizer zinc phthalocyanine (ZnPc) for simultaneous near-infrared fluorescence imaging and photodynamic therapy. Both in vitro and in vivo studies indicated that the both Dox and ZnPc-loaded FMLM (Dox/ZnPc-FMLM) exhibited the enhanced tumor accumulation, increased cellular uptake, improved anticancer activity, and weaked side effects compared with Dox/ZnPc-Fe3O4@mSiO2@lipid-PEG nanoparticle (Dox/ZnPc-FML) and free drug. For the first time, magnet targeting cooperative with methotrexate macromolecular prodrug targeting is successfully exploited to develop a promising versatile theranostic nanoplatform for dual-modal fluorescence and magnetic resonance imaging-guided combined chemo-photodynamic cancer therapy.

Dual-modal fluorescence and light-scattering sensor based on water-soluble carbon dots for silver ions detection

A facile fluorometric and light-scattering dual-modal nanosensor for silver(i) ions detection was established based on target-responsive aggregation of carbon dots/cysteine system.

A graphene quantum dot@Fe3O4@SiO2 based nanoprobe for drug delivery sensing and dual-modal fluorescence and MRI imaging in cancer cells

A novel graphene quantum dot (GQD)@Fe3O4@SiO2 based nanoprobe was reported for targeted drug delivery, sensing, dual-modal imaging and therapy. Carboxyl-terminated GQD (C-GQD) was firstly conjugated with Fe3O4@SiO2 and then functionalized with cancer targeting molecule folic acid (FA). DOX drug molecules were then loaded on GQD surface of Fe3O4@SiO2@GQD-FA nanoprobe via pi-pi stacking, which resulted in Fe3O4@SiO2@GQD-FA/DOX conjugates based on a FRET mechanism with GQD as donor molecules and DOX as acceptor molecules. Meanwhile, we successfully performed in vitro MRI and fluorescence imaging of living Hela cells and monitored intracellular drug release process using this Fe3O4@SiO2@GQD-FA/DOX nanoprobe. Cell viability study demonstrated the low cytotoxicity of Fe3O4@SiO2@GQD-FA nanocarrier and the enhanced therapeutic efficacy of Fe3O4@SiO2@GQD-FA/DOX nanoprobe for cancer cells. This luminomagnetic nanoprobe will be a potential platform for cancer accurate diagnosis and therapy.

GW27-e0892 In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles

GW27-e0892 In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles

Enhanced near-infrared photoacoustic imaging of silica-coated rare-earth doped nanoparticles

Near-infrared photoacoustic (PA) imaging is an emerging diagnostic technology that utilizes the tissue transparent window to achieve improved contrast and spatial resolution for deep tissue imaging. In this study, we investigated the enhancement effect of the SiO2 shell on the PA property of our core/shell rare-earth nanoparticles (REs) consisting of an active rare-earth doped core of NaYF4:Yb,Er (REDNPs) and an undoped NaYF4 shell. We observed that the PA signal amplitude increased with SiO2 shell thickness. Although the SiO2 shell caused an observed decrease in the integrated fluorescence intensity due to the dilution effect, fluorescence quenching of the rare earth emitting ions within the REDNPs cores was successfully prevented by the undoped NaYF4 shell. Therefore, our multilayer structure consisting of an active core with successive functional layers was demonstrated to be an effective design for dual-modal fluorescence and PA imaging probes with improved PA property. The result from this work addresses a critical need for the development of dual-modal contrast agent that advances deep tissue imaging with high resolution and signal-to-noise ratio.

Gadolinium-doped carbon dots with high quantum yield as an effective fluorescence and magnetic resonance bimodal imaging probe

It is highly desired to develop the dual-modality fluorescence and magnetic resonance imaging (MRI) probes in medical imaging because it can provide high-resolution macroscopical anatomical information and high-sensitivity microscopical optical signal simultaneously. In this study, harmless gadolinium-doped carbon dots (Gd-CDs) were prepared via a convenient one-pot hydrothermal approach for fluorescence/MR bimodal imaging. The derived Gd-CDs exhibit enhanced blue photoluminescence with a quantum yield as high as 69.86% and significantly improved longitudinal relaxivity (r1 = 14.33 mM−1 s−1, 0.5 T) in comparison with commercial Magnevist (Gd-DTPA, r1 = 4.5 mM−1 s−1, 0.5 T). Here Gd3+ ions are simply chelated onto CDs by carboxyl groups. Moreover, unlike the previous reports, Gd3+ chelation does not perturb core optical properties of CDs. Excellent water solubility, good cell-membrane permeability and negligible cytotoxicity make Gd-CDs an ideal dual-modal fluorescence/MR imaging nanoprobe, suggesting its potential and significance in practical biological and clinic applications in the future.

Fluorescence ON–OFF switching using micelle of stimuli-responsive double hydrophilic block copolymers: Nile Red fluorescence in micelles of poly(acrylic acid-b-N-isopropylacrylamide)

The dual-mode fluorescence ON–OFF switching of Nile Red (NR) by using stimuli-responsive polymeric micelle of poly(acrylic acid-b-N-isopropylacrylamide) (PAA-b-PNIPAM) has been studied. PAA-b-PNIPAM, one of double hydrophilic block copolymers, is known to form PNIPAM-core/PAA-corona micelles in aqueous solutions when the temperature of the solution is elevated up to the lower critical solution temperature (LCST) of PNIPAM block. It also forms PAA-core/PNIPAM-corona micelles when the anionic PAA block is charge-neutralized with cationic cetyltrimethylammonium ion. Fluorescence properties of NR in the micelles are elucidated by observing various fluorescence parameters such as intensity, polarization, and quantum yield. It is found that the fluorescence intensity is negligibly low (OFF-state) when PAA-b-PNIPAM exists as a form of unimer, whereas it is remarkably enhanced (ON-state) when the PNIPAM-core or PAA-core micelles are formed. These results demonstrate that a novel fluorescence ON–OFF switching system can be constructed by using PAA-b-PNIPAM micelles and NR.

Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging.

Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG)ylated, reduced nano-graphene oxide nanocomposite (rNGO-PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1288-x) contains supplementary material, which is available to authorized users.

Chitosan hybrid nanoparticles as a theranostic platform for targeted doxorubicin/VEGF shRNA co-delivery and dual-modality fluorescence imaging

Chitosan hybrid nanoparticles were fabricated as a targeted drug/gene co-delivery nanovector for potential cancer therapy and dual-modality fluorescence imaging.

In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles.

Aims: This study aims to explore non-invasive imaging of atherosclerotic plaque through magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) by using profilin-1 targeted magnetic iron oxide nanoparticles (PF1-Cy5.5-DMSA-Fe3O4-NPs, denoted as PC-NPs) as multimodality molecular imaging probe in murine model of atherosclerosis. Methods and Results: PC-NPs were constructed by conjugating polyclonal profilin-1 antibody and NHS-Cy5.5 fluorescent dye to the surface of DMSA-Fe3O4-nanoparticles via condensation reaction. Murine atherosclerosis model was induced in apoE-/- mice by high fat and cholesterol diet (HFD) for 16 weeks. The plaque areas in aortic artery were detected with Oil Red O staining. Immunofluorescent staining and Western blot analysis were applied respectively to investigate profilin-1 expression. CCK-8 assay and transwell migration experiment were performed to detect vascular smooth muscle cells (VSMCs) proliferation. In vivo MRI and NIRF imaging of atherosclerotic plaque were carried out before and 36 h after intravenous injection of PC-NPs. Oil Red O staining showed that the plaque area was significantly increased in HFD group (p<0.05). Immunofluorescence staining revealed that profilin-1 protein was highly abundant within plaque in HFD group and co-localized with α-smooth muscle actin. Profilin-1 siRNA intervention could inhibit VSMCs proliferation and migration elicited by ox-LDL (p<0.05). In vivo MRI and NIRF imaging revealed that PC-NPs accumulated in atherosclerotic plaque of carotid artery. There was a good correlation between the signals of MRI and ex vivo fluorescence intensities of NIRF imaging in animals with PC-NPs injection. Conclusion: PC-NPs is a promising dual modality imaging probe, which may improve molecular diagnosis of plaque characteristics and evaluation of pharmaceutical interventions for atherosclerosis.

Stimulus Response of Au-NPs@GMP-Tb Core-Shell Nanoparticles: Toward Colorimetric and Fluorescent Dual-Mode Sensing of Alkaline Phosphatase Activity in Algal Blooms of a Freshwater Lake.

In this study, we demonstrate a colorimetric and fluorescent dual-mode method for alkaline phosphatase activity (APA) sensing in freshwater lake with stimuli-responsive gold nanoparticles@terbium-guanosine monophosphate (Au-NPs@GMP-Tb) core-shell nanoparticles. Initially, the core-shell nanoparticles were fabricated based on Au-NPs decorated with a fluorescent GMP-Tb shell. Upon being excited at 290 nm, the as-formed Au-NPs@GMP-Tb core-shell nanoparticles emit green fluorescence, and the decorated GMP-Tb shell causes the aggregation of Au-NPs. However, the addition of ALP destroys GMP-Tb shell, resulting in the release of Au-NPs from the shell into the solvent. As a consequence, the aggregated Au-NPs solubilizes with the changes in the UV-vis spectrum of the dispersion, and in the meantime, the fluorescence of GMP-Tb shell turns off, which constitutes a new mechanism for colorimetric and fluorescent dual-mode sensing of APA. With the method developed here, we could monitor the dynamic change of APA during an algal bloom of a freshwater lake, both by the naked eye and further confirmed by fluorometric determination. This study not only offers a new method for on-site visible detection of APA but also provides a strategy for dual-mode sensing mechanisms by the rational design of the excellent optical properties of Au-NPs and the adaptive inclusion properties of the luminescent infinite coordination polymers.

In vivo molecular imaging of colorectal cancer using quantum dots targeted to vascular endothelial growth factor receptor 2 and optical coherence tomography/laser-induced fluorescence dual-modality imaging.

Optical coherence tomography/laser induced fluorescence (OCT/LIF) dual-modality imaging allows for minimally invasive, nondestructive endoscopic visualization of colorectal cancer in mice. This technology enables simultaneous longitudinal tracking of morphological (OCT) and biochemical (fluorescence) changes as colorectal cancer develops, compared to current methods of colorectal cancer screening in humans that rely on morphological changes alone. We have shown that QDot655 targeted to vascular endothelial growth factor receptor 2 (QD655-VEGFR2) can be applied to the colon of carcinogen-treated mice and provides significantly increased contrast between the diseased and undiseased tissue with high sensitivity and specificity ex vivo. QD655-VEGFR2 was used in a longitudinal in vivo study to investigate the ability to correlate fluorescence signal to tumor development. QD655-VEGFR2 was applied to the colon of azoxymethane (AOM-) or saline-treated control mice in vivo via lavage. OCT/LIF images of the distal colon were taken at five consecutive time points every three weeks after the final AOM injection. Difficulties in fully flushing unbound contrast agent from the colon led to variable background signal; however, a spatial correlation was found between tumors identified in OCT images, and high fluorescence intensity of the QD655 signal, demonstrating the ability to detect VEGFR2 expressing tumors in vivo.