Novel Near-infrared Research Articles

In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, λem: 858 nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P < 0.05). In vivo optical imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 ± 0.3 [MT1-hIC7L] vs 3.1 ± 0.2 [hIC7L] 48 h after administration, P < 0.05), while the probes showed similarly low fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors.

Efficient near-infrared down-conversion in KCaGd(PO_4)_2:Ce^3+,Yb^3+

Abstract: A novel near-infrared (NIR) quantum cutting KCaGd(PO4)2:Ce3+,Yb3+ phosphor was successfully developed. Due to the cooperative energy transfer from one Ce3+ to two Yb3+, an intense NIR emission around 1021 nm of Yb3+:2F5/2-2F7/2 transition was obtained under 324 nm excitation. Yb3+ concentration dependent quantum efficiency has been calculated and the theoretical maximum efficiency approaches up to 158.2%. Because the emission of Yb3+ around 1021 nm is matched with the band gap of crystalline Si, the phosphors could be a potential candidate for silicon-based solar cells.

Biomedical Imaging of Colorectal Cancer by Near Infrared Fluorescent Nanoparticles

In this paper we describe the preparation of novel Near Infrared (NIR) fluorescent nanoparticles for application in medical imaging of colorectal tumors. The nanoparticles are prepared by using only non-covalent binding processes of molecules which are approved for clinical use. The preparation process is based on the precipitation of a polycation, Eudragit-RS, followed by sequential adsorption of a blocking protein, sodium caseinate, NIR fluorescent dye, Indocyanine Green (ICG) and optionally, a targeting molecule, anti-CEA antibody. Fluorescence measurements have shown that these nanoparticles have higher resistance to photobleaching and higher quantum yield relatively to free ICG. Imaging experiments in orthotopic colorectal cancer mice models have shown that these fluorescent nanoparticles are capable of binding to LS174T human colon tumors in vivo with high specificity, even without the targeting molecule. These nanoparticles, composed of all FDA approved materials, open the way to clinical bioimaging and diagnostics of colon cancer.

A near-infrared turn-on fluorescent nanosensor for zinc(II) based on CuInS2 quantum dots modified with 8-aminoquinoline

We describe a novel near-infrared (NIR) “turn-on” fluorescent nanosensor for highly sensitive and selective detection of Zn(II) ion. It is based on the use of the fluorescent probe 8-aminoquinoline conjugate to CuInS2 quantum dots. Water-soluble CuInS2 QDs capped by mercaptopropionic acid (MPA) were synthesized in aqueous solution via a hydrothermal method, and the carboxy groups on the surface of the capped QDs were then covalently linked to the amino groups of the probe 8-aminoquinoline to form the conjugate acting as a nanosensor. The fluorescence of the modified QDs is almost completely quenched via a hole-transfer mechanism. If, however, Zn(II) is added, the lone pair electrons of the nitrogen atom of 8-aminoquinoline become involved into the mechanism of binding Zn(II), and hole-transfer quenching is suppressed which results in turn-on fluorescence. The nanoprobe enables Zn(II) to be determined by measurement of the increase in fluorescence intensity. Under optimized experimental conditions, the nanosensor displays a wide and fairly linear response in the 0.005 to 1 mM concentration range, with a 4.5 μM detection limit. The nanosensor reported here was successfully employed to the detection of Zn(II) in spiked tap water samples.

Synthesis and evaluation of new NIR-fluorescent probes for cathepsin B: ICT versus FRET as a turn-ON mode-of-action

Recent years have seen tremendous progress in the design and study of molecular imaging geared towards biological and biomedical applications. The expression or activity of specific enzymes including proteases can be monitored by cutting edge molecular imaging techniques. Cathepsin B plays key roles in tumor progression via controlled degradation of extracellular matrix. Consequently, this protease has been attracting significant attention in cancer research, and many imaging probes targeting its activity have been developed. Here, we describe the design, synthesis and evaluation of two novel near infrared (NIR) fluorescent probes for detection of cathepsin B activity with different turn-ON mechanisms. One probe is based on an ICT activation mechanism of a donor-two-acceptor π-electron dye system, while the other is based on the FRET mechanism obtained by a fluorescent dye and a quencher. The two probes exhibit significant fluorescent turn-ON response upon cleavage by cathepsin B. The NIR fluorescence of the ICT probe in its OFF state was significantly lower than that of the FRET-based probe. This effect results in a higher signal-to-noise ratio and consequently increased sensitivity and better image contrast.

Multiplicate sensitization of novel near-infrared luminescent linear copolymers based on Er, Nd and Yb-complexes

A series of novel near-infrared (NIR) luminescent linear copolymers (PCzLnQL2) covalently linked with Ln-complexes were synthesized and characterized. The copolymers show broadband sensitized and highly efficient NIR luminescence.

Observation of Atherosclerotic Plaque Phantoms through Saline or Blood Layers by Near-Infrared Hyperspectral Imaging

We observed atherosclerotic plaque phantoms using a novel near-infrared (NIR) hyperspectral imaging (HSI) technique. Data were obtained through saline or blood layers to simulate an angioscopic environment for the phantom. For the study, we developed a NIR-HSI system with an NIR supercontinuum light source and mercury-cadmium-telluride camera. Apparent spectral absorbance was obtained at wavelengths of 1150 - 2400 nm. Hyperspectral images of lipid were constructed using a spectral angle mapper algorithm. Bovine fat covered with saline or blood was observed using hyperspectral images at a wavelength around 1200 nm. Our results show that NIR-HSI is a promising angioscopic technique with the potential to identify lipid-rich plaques without clamping and saline injection.

Non-Invasive In Vivo Imaging of Near Infrared-labeled Transferrin in Breast Cancer Cells and Tumors Using Fluorescence Lifetime FRET

The conjugation of anti-cancer drugs to endogenous ligands has proven to be an effective strategy to enhance their pharmacological selectivity and delivery towards neoplasic tissues. Since cell proliferation has a strong requirement for iron, cancer cells express high levels of transferrin receptors (TfnR), making its ligand, transferrin (Tfn), of great interest as a delivery agent for therapeutics. However, a critical gap exists in the ability to non-invasively determine whether drugs conjugated to Tfn are internalized into target cells in vivo. Due to the enhanced permeability and retention (EPR) effect, it remains unknown whether these Tfn-conjugated drugs are specifically internalized into cancer cells or are localized non-specifically as a result of a generalized accumulation of macromolecules near tumors. By exploiting the dimeric nature of the TfnR that binds two molecules of Tfn in close proximity, we utilized a Förster Resonance Energy Transfer (FRET) based technique that can discriminate bound and internalized Tfn from free, soluble Tfn. In order to non-invasively visualize intracellular amounts of Tfn in tumors through live animal tissues, we developed a novel near infrared (NIR) fluorescence lifetime FRET imaging technique that uses an active wide-field time gated illumination platform. In summary, we report that the NIR fluorescence lifetime FRET technique is capable of non-invasively detecting bound and internalized forms of Tfn in cancer cells and tumors within a live small animal model, and that our results are quantitatively consistent when compared to well-established intensity-based FRET microscopy methods used in in vitro experiments.

Expanding Multimodal Microscopy by High Spectral Resolution Coherent Anti-Stokes Raman Scattering Imaging for Clinical Disease Diagnostics

Over the past years fast label-free nonlinear imaging modalities providing molecular contrast of endogenous disease markers with subcellular spatial resolution have been emerged. However, applications of these imaging modalities in clinical settings are still at the very beginning. This is because single nonlinear imaging modalities such as second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) have only limited value for diagnosing diseases due to the small number of endogenous markers. Coherent anti-Stokes Raman scattering (CARS) microscopy on the other hand can potentially be added to SHG and TPEF to visualize a much broader range of marker molecules. However, CARS requires a second synchronized laser source and the detection of a certain wavenumber range of the vibrational spectrum to differentiate multiple molecules, which results in increased experimental complexity and often inefficient excitation of SHG and TPEF signals. Here we report the application of a novel near-infrared (NIR) fiber laser of 1 MHz repetition rate, 65 ps pulse duration, and 1 cm(-1) spectral resolution to realize an efficient but experimentally simple SGH/TPEF/multiplex CARS multimodal imaging approach for a label-free characterization of composition of complex tissue samples. This is demonstrated for arterial tissue specimens demonstrating differentiation of elastic fibers, triglycerides, collagen, myelin, cellular cytoplasm, and lipid droplets by analyzing the CARS spectra within the C-H stretching region only. A novel image analysis approach for multispectral CARS data based on colocalization allows correlating spectrally distinct pixels to morphologic structures. Transfer of this highly precise but compact and simple to use imaging approach into clinical settings is expected in the near future.

Application of near infrared diffuse correlation spectroscopy in noninvasive monitoring of tumor photodynamic therapy

A novel near-infrared (NIR) diffuse correlation spectroscopy (DCS) has recently been developed for noninvasive monitoring of tumor blood flow during photodynamic therapy (PDT).DCS offers several attractive new features for tumor blood flow measurement such as noninvasiveness,portability,low cost,high temporal resolution and relatively large penetration depth.DCS technology has been utilized for continuous measurement of tumor blood flow before,during and after PDT in both animals and humans.The ultimate goal is to predict treatment outcomes from the measured tumor hemodynamic responses to PDT. Key words: Diffusion; Correlation; Spectroscopy; Blood flow; Cancer; Photodynamic therapy

Near-infrared downconversion in Eu2+ and Pr3+ co-doped KSrPO4 phosphor

A novel near-infrared (NIR) downconversion (DC) phosphor KSrPO4:Eu2+, Pr3+ is synthesized by the conventional high temperature solid-state reaction. The Eu2+ acts as an efficient sensitizer for Pr3+ in the KSrPO4 host. With broadband near-ultraviolet light excitation induced by the 4f→5d transition of Eu2+, the characteristic NIR emission of Pr3+, peaking at 974 nm and 1019 nm due to 3P0→1G4 and 1G4→3H4 transitions, is generated as a result of the energy transfer from Eu2+ to Pr3+. The luminescence spectra in both the visible and the NIR regions and the decay lifetime curves of Eu2+ prove the energy transfer from Eu2+ to Pr3+. This Eu2+ and Pr3+ co-doped KSrPO4 phosphor may be a promising candidate to modify the spectral mismatch behavior of crystalline solar cells and sunlight.

A novel near-infrared fluorescent probe for selectively sensing nitroreductase (NTR) in an aqueous medium

A novel near-infrared (NIR) fluorescent probe based on cyanine dyes was designed and synthesized to detect nitroreductase (NTR) activity. Upon reaction with NTR, the nitro-group of p-nitrobenzyl moiety was reduced to amino-group and therefore renews the π-electron conjugation of the dye, resulting in the intense NIR fluorescent emission (708 nm). This redox-induced NIR-fluorescence probe has been successfully applied to the detection of NTR activity under physiological conditions with high selectivity.

Near-infrared photocatalysis of β-NaYF4:Yb3+,Tm3+@ZnO composites

A novel near-infrared (NIR)-responsive photocatalyst, β-NaYF4:Yb(3+),Tm(3+)@ZnO composites, was prepared by a two-step high temperature thermolysis method. In the NIR-responsive photocatalysis, β-NaYF4:Yb,Tm served as a NIR-to-UV upconverter and provided "UV light" or "necessary energy" to the ZnO catalyst. The energy transfer in the composites and the mixtures of β-NaYF4:Yb,Tm and ZnO was studied by using steady-state and dynamic fluorescence spectroscopy. The NIR photocatalytic activities were investigated by the decomposition of Rhodamine B. It was found that the energy transfer processes dominated the overall photocatalytic activities, and the generation of hydroxyl radicals was the origin of organic pollutant decomposition under NIR irradiation.

Near-infrared photocatalyst of Er3+/Yb3+ codoped (CaF2@TiO2) nanoparticles with active-core/active-shell structure

A novel near-infrared (NIR) photocatalyst of Er3+/Yb3+-(CaF2@TiO2) was synthesized with optically active centers (Er3+/Yb3+) presented both in the CaF2 cores and TiO2 shells, and the corresponding upconversion luminescence properties increased greatly, which was helpful for the organic dye solution removal efficiency under NIR irradiation.

Preparation and characterization of phospholipid-conjugated indocyanine green as a near-infrared probe

We have rationally designed and synthesized a novel near-infrared (NIR) photoactivating probe, designated by iDOPE, in which an indocyanine green (ICG) fluorophore is covalently conjugated with a phospholipid moiety, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), to incorporate into liposome bilayers. NIR irradiation showed that iDOPE retained the optical and fluorescence properties of ICG and demonstrated photoactivator characteristics: fluorescence emission at around 820nm in a solvent, singlet oxygen production, and concentration-dependent heat generation. Additionally, iDOPE was incorporated into liposome bilayers and maintained stable liposomally formulated iDOPE (LP-iDOPE) over 1week under physiological conditions. We also observed the tumor-specific biodistribution of LP-iDOPE of in vivo xenografts. These findings suggest that LP-iDOPE might be a promising tool for NIR optical imaging, photodynamic therapy, and photothermal therapy.

New Trick for an Old Ligand! The Sensing of Zn(II) Using a Lanthanide Based Ternary Yb(III)-cyclen-8-hydroxyquinoline System As a Dual Emissive Probe for Displacement Assay

A novel near-infrared (NIR) emissive lanthanide-based zinc sensor was designed, based on the self-assembly in aqueous solution between the nonemissive coordinatively unsaturated Yb(III) cyclen complex 2·Yb and the sulfonated 8-hydroxyquinoline (8-HQS) chromophore, which was employed as a sensitizing antenna. The resulting ternary complex, 2·Yb·8-HQS, displayed metal-centered emission in the NIR range upon excitation of the antenna with high quantum yield of Q = 0.23 ± 0.03% in pH 7.4 buffered aqueous solution; demonstrating efficient sensitization from 8-HQS. The addition of zinc led to quenching of the NIR emission as a result of the dissociation of the luminescent ternary 2·Yb·8-HQS complex, where the 8-HQS antenna was displaced from the Yb(III) center in favor of the formation of more stable chelates with Zn(II). These newly formed Zn(II) complexes were shown to exhibit strong green fluorescence; allowing for the simultaneous sensing of Zn(II) both within the visible and the NIR regions at physiological pH in competitive media. Furthermore, 2·Yb·8-HQS was shown to be able to detect Zn(II) with good selectivity and in a reversible manner, even in the presence of competitive group (I) and (II) metal ions as well as in the presence of several biologically important d-metal ions.

Development of NIR Fluorescent Dyes Based on Si–rhodamine for in Vivo Imaging

We have developed a series of novel near-infrared (NIR) wavelength-excitable fluorescent dyes, SiR-NIRs, by modifying the Si-rhodamine scaffold to obtain emission in the range suitable for in vivo imaging. Among them, SiR680 and SiR700 showed sufficiently high quantum efficiency in aqueous media. Both antibody-bound and free dye exhibited high tolerance to photobleaching in aqueous solution. Subcutaneous xenograft tumors were successfully visualized in a mouse tumor model using SiR700-labeled anti-tenascin-C (TN-C) antibody, SiR700-RCB1. SiR-NIRs are expected to be useful as labeling agents for in vivo imaging studies including multicolor imaging, and also as scaffolds for NIR fluorescence probes.

2-Nitroimidazole-Tricarbocyanine Conjugate as a Near-Infrared Fluorescent Probe for in Vivo Imaging of Tumor Hypoxia

We developed a novel near-infrared (NIR) fluorescent probe, GPU-167, for in vivo imaging of tumor hypoxia. GPU-167 comprises a tricarbocyanine dye as an NIR fluorophore and two 2-nitroimidazole moieties as exogenous hypoxia markers that undergo bioreductive activation and then selective entrapment in hypoxic cells. After treatment with GPU-167, tumor cells contained significantly higher levels of fluorescence in hypoxia than in normoxia. In vivo fluorescence imaging specifically detected GPU-167 in tumors 24 h after administration. Ex vivo analysis revealed that fluorescence showed a strong correlation with hypoxia inducible factor (HIF)-1 active hypoxic regions. These data suggest that GPU-167 is a promising in vivo optical imaging probe for tumor hypoxia.

Novel near-infrared luminescent linear copolymer based on tris(8-hydroxyquinoline)erbium

A novel near-infrared (NIR) luminescent linear copolymer based on tris(8-hydroxyquinoline)erbium (ErQ3), PCzErQ3, was synthesized and characterized. The copolymer had appropriate molecular weight as well as good solubility in common organic solvents. The glass transition temperature (Tg) and the temperature of 5% weight loss (Td) for the copolymer were 200°C and 368°C respectively, indicating that the copolymer had excellent thermal stability. Absorption and photoluminescence (PL) spectra of the copolymer were recorded and PL decay analysis was measured. Excited at the absorption band of carbazole (235, 265 and 295nm) and metalloquinolate (390nm), the copolymer emitted the characteristic NIR-luminescence of ErIII ion. The result indicates that the energy absorbed by carbazole (light-harvesting group) was transferred to 8-hydroxyquinoline (coordination group), where it is finally transferred to ErIII ion. In addition, the full width at half maximum (FWHM) centered at 1525nm in the PL emission spectrum of the copolymer was 92nm, which enabled a wide gain bandwidth for optical amplification.

Design of NIR-Absorbing Simple Asymmetric Squaraine Dyes Carrying Indoline Moieties for Use in Dye-Sensitized Solar Cells with Pt-Free Electrodes

Novel near-infrared (NIR)-sensitizing (up to 800 nm) simple asymmetric squaraine dyes (Sq 31 and Sq 33) carrying indoline moieties that did not require the introduction of any linker groups were developed. DSSCs fabricated with Sq 33 exhibited remarkable characteristics in the long-wavelength visible and NIR region (up to 800 nm), such as a conversion efficiency of 3.75% (AM 1.5G) with an incident photon-to-current conversion efficiency of 63% (650 nm), a short-circuit photocurrent density of 13.64 mA, an open-circuit photovoltage of 0.48, and a fill factor of 0.57.