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.     

A dual-modal probe for NIR fluorogenic and ratiometric photoacoustic imaging of Cys/Hcy in vivo

Biothiols, such as cysteine(Cys) and homocysteine(Hcy), play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems. Therefore, the in vivo detection of biothiols is of great importance for early diagnosis of diseases and assessment of disease progression. In this work, we developed a near-infrared(NIR) fluorescence and photoacoustic dual-modal molecular probe(NIR-S) that can be specifically activated by Cys or Hcy. The aryl-thioether substituted cyanine probe can undergo nucleophilic substitution and Smiles rearrangement reaction, resulting in specific turn-on NIR fluorescence and ratiometric photoacoustic responses for Hcy/Cys. Thus, NIR-S not only realizes the specific NIR fluorescence and photoacoustic dual mode imaging to detect Hcy/Cys in solution, but also can be applied to living cells and mice to detect Hcy/Cys. This work provided a practical tool to detect Hcy/Cys levels in vivo, which would be beneficial for the early diagnosis and progress of diseases.     

In vivo NIR imaging with CdTe/CdSe quantum dots entrapped in PLGA nanospheres

Luminescent near-infrared (NIR) CdTe/CdSe QDs were synthesized and encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanospheres to prepare stable and biocompatible QDs-loaded nanospheres for in vivo imaging. QDs were encapsulated with PLGA nanospheres by a solid dispersion method and optimized to have high fluorescence intensity for in vivo imaging detection. The resultant QDs-loaded PLGA nanospheres were characterized by various analytical techniques such as UV-Vis measurement, dynamic light scattering (DLS), fluorescence spectroscopy, and transmission electron microscopy (TEM). Finally, we evaluated toxicity and body distribution of QDs loaded in PLGA nanospheres in vitro and in vivo, respectively. From the results, the QDs loaded in PLGA nanospheres were spherical and showed a diameter range of 135.0-162.3 nm in size. The QD nanospheres increased their stability against photooxidation and photobleaching, which have the high potential for applications in biomedical imaging. We have also attained non-invasive in vivo imaging with light photons, representing an intriguing avenue for obtaining biological information by the use of NIR light.     

Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probes

The development of small-molecule inhibitors for perturbing enzyme function requires assays to confirm that the inhibitors interact with their enzymatic targets in vivo. Determining target engagement in vivo can be particularly challenging for poorly characterized enzymes that lack known biomarkers (e.g., endogenous substrates and products) to report on their inhibition. Here, we describe a competitive activity-based protein profiling (ABPP) method for measuring the binding of reversible inhibitors to enzymes in animal models. Key to the success of this approach is the use of activity-based probes that show tempered rates of reactivity with enzymes, such that competition for target engagement with reversible inhibitors can be measured in vivo. We apply the competitive ABPP strategy to evaluate a newly described class of piperazine amide reversible inhibitors for the serine hydrolases LYPLA1 and LYPLA2, two enzymes for which selective, in vivo active inhibitors are lacking. Competitive ABPP identified individual piperazine amides that selectively inhibit LYPLA1 or LYPLA2 in mice. In summary, competitive ABPP adapted to operate with moderately reactive probes can assess the target engagement of reversible inhibitors in animal models to facilitate the discovery of small-molecule probes for characterizing enzyme function in vivo.     

New directions for dehydrocyclodimerization of piperylene

Russian Chemical Bulletin -     

A nonpeptidic cathepsin S activity-based probe for noninvasive optical imaging of tumor-associated macrophages

Macrophage infiltration into tumors has been correlated with poor clinical outcome in multiple cancer types. Therefore, tools to image tumor-associated macrophages could be valuable for diagnosis and prognosis of cancer. Herein, we describe the synthesis and characterization of a cathepsin S-directed, quenched activity-based probe (qABP), BMV083. This probe makes use of an optimized nonpeptidic scaffold leading to enhanced in vivo properties relative to previously reported peptide-based probes. In a syngeneic breast cancer model, BMV083 provides high tumor-specific fluorescence that can be visualized using noninvasive optical imaging methods. Furthermore, analysis of probe-labeled cells demonstrates that the probe primarily targets macrophages with an M2 phenotype. Thus, BMV083 is a potential valuable in vivo reporter for tumor-associated macrophages that could greatly facilitate the future studies of macrophage function in the process of tumorigenesis.     

New directions in isotachophoresis

The great flexibility, reproducibility, accuracy and extremely low running costs of isotachophoresis make it an attractive alternative to HPLC for a number of applications. Recent developments in isotachophoresis equipment, detection systems and the advent of the microprocessor have enhanced the technique's capabilities.     

Two-photon Lysotrackers for in vivo imaging

We report two-photon Lysotrackers (CLT-blue and CLT-yellow) that can be excited by 750-840 nm femtosecond laser pulses and emit at 470 and 550 nm, respectively. They can be easily loaded into cells and tissue slices for visualization of lysosomes in live cells and tissues for a long period of time through two-photon microscopy. When combined with appropriate two-photon probes for other biological targets, these novel probes would greatly facilitate the two-photon microscopy colocalization experiments.     

Plasmonic nanoprobes for intracellular sensing and imaging

Recent advances in integrating nanotechnology and optical microscopy offer great potential in intracellular applications with improved molecular information and higher resolution. Continuous efforts in designing nanoparticles with strong and tunable plasmon resonance have led to new developments in biosensing and bioimaging, using surface-enhanced Raman scattering and two-photon photoluminescence. We provide an overview of the nanoprobe design updates, such as controlling the nanoparticle shape for optimal plasmon peak position; optical sensing and imaging strategies for intracellular nanoparticle detection; and addressing practical challenges in cellular applications of nanoprobes, including the use of targeting agents and control of nanoparticle aggregation.

Design of sodium lanthanide fluoride nanocrystals for NIR imaging and targeted therapy

Since the 18th century, rare-earth ions have been widely used as active dopants in inorganic lattices due to their unique optical properties. Rare-earth doping can control the crystal phase, morphology and size of nanomaterials, resulting in adjustable optical response of doped nanomaterials. The substrate of nanostructures can greatly affect the physical and chemical behavior of rare-earth ions. Therefore, it is also important to find suitable host materials. Among various new host materials, sodium lanthanide fluoride (NaLnF₄) nanoparticles are known for their photoluminescence properties and stability. This paper emphasizes the latest progress of NaLnF₄ and its derivatives nanoparticles and their related applications in various biological fields. This review covers the key criteria of NaLnF₄ and its derivatives, including basic electronic structure, lattice environment, doping strategy, surface functionalization and basic design principles for biological applications. At the same time, this paper also discusses the obstacles encountered in the development process and the research directions and challenges of future new applications.     

NIR imaging spectroscopy for quantification of constituents in polymers thin films loaded with paracetamol

Thin films loaded with the drug paracetamol were produced from polymer blends formed by hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyethyleneglycol (PEG), at various mass ratios of polymers and drug defined by a d-optimal experimental design. NIR hyperspectral images were obtained from each thin film formulation and the pixel-to-pixel quantification of the constituents were carried out by partial least square (PLS) and multivariate curve resolution–alternating least square (MCR-ALS) with three different calibration/validation strategies. These strategies differ in the way to construct the calibration and validation matrices and they had to be carried out to suppress the bias on the quantification of the constituents in the polymer blend. The errors of prediction in the models from MCR-ALS were influenced by the calibration/validation strategy employed, but they were similar to the ones from PLS model. Concentration distribution maps were built after pixel-to-pixel predictions and their characteristics were analyzed.     

New glowing dyes in vivo imaging with wavelengths beyond 1500 nm

<正>Near-infrared (NIR) fluorescence imaging in the second near-infrared region (NIR-II, 1000–1700 nm) is an important and attractive imaging method for biomedical research and clinical applications, and can achieve high spatial resolution,high signal-to-background ratio (SBR) and deeper tissue imaging owing to nearly zero auto-fluorescence background and tissue scattering [1,2]. Smaller optical sub-window such as NIR-IIb (1500–1700 nm) has provided significant im-     

New Polyfluorinated Cyanine Dyes for Selective NIR Staining of Mitochondria

In this communication, the synthesis of three unknown polyfluorinated cyanine dyes and their application as selective markers for mitochondria are presented. By incorporating fluorous side chains into cyanine dyes, their remarkable photophysical properties were enhanced. To investigate their biological application, several different cell lines were incubated with the synthesized cyanine dyes. It was discovered that the presented dyes can be utilized for selective near-infrared-light (NIR) staining of mitochondria, with very low cytotoxicity determined by MTT assay. This is the first time that polyfluorinated cyanine fluorophores are presented as selective markers for mitochondria. Due to the versatile applications of polyfluorinated fluorophores in bioimaging and materials science, it is expected that the presented fluorophores will be stimulating for the scientific community.     

Characteristics of several NIR tuneable diode lasers for spectroscopic based gas sensing: a comparison

Tuneable laser diodes were characterized and compared for use as tuneable sources in gas absorption spectroscopy. Specifically, the characteristics of monolithic widely tuneable single frequency lasers, such as sampled grating distributed Bragg reflector laser and modulated grating Y-branch laser diodes, recently developed for optical communications, with operating wavelengths in the 1,520 nm相似文献   

New directions of matrix ir-spectroscopy

By use of thermal molecular beam IR matrix spectroscopy and IR irradiation in selected frequency ranges the vibrational spectra of conformers of 1,2-difluoroethane and methylvinylether will be discussed. The former molecule affords a case, where by comparison of CO₂ laser and 3000 cm^?1 irradiation the barriers to interconversion gauche?trans may be estimated. Methylvinylether on the other hand is a molecule, whose conformers may be interconverted by a 1-photon process in the 3000 cm^?1 region, but not by photons with frequency lower than 1400 cm^?1.     

A capillary-PDMS hybrid chip for separations-based sensing of neurotransmitters in vivo

A chip fabricated by multilayer soft lithography of poly(dimethylsiloxane) was created for separations-based sensing of neurotransmitters in vivo. The chip incorporated a pneumatically actuated peristaltic pump and valving system to combine low-flow push-pull perfusion sampling, on-line derivatization, and flow-gated injection onto an embedded fused-silica capillary for high speed separation of amine neurotransmitters from the brain of living animals. Six 160 microm wide by 10 microm high control channels, actuated with an overlapping 60 degrees pulse sequence, simultaneously drove sample and buffers through fluidic channels of the same dimensions. Tunable sampling flow rates of 40 to 130 nL min(-1) and separation buffer flow rates of 380 to 850 nL min(-1) were achieved with actuation frequencies between 3 and 10 Hz. On-line sampling of amine neurotransmitters with separation efficiencies in excess of 250,000 plates, detection limits of approximately 40 nM, and relative standard deviations of 4% for glutamate and aspartate were achieved in vitro. Electropherograms with resolution of gamma-aminobutyric acid, glutamine, taurine, serine, glycine, o-phosphorylethanolamine, glutamate, and aspartate could be collected every 30 s for over 4 h in vivo. It was also shown that pharmacological agents could be delivered and subsequent changes in neurotransmitter profile could be measured when delivering either 70 mM K+ artificial cerebrospinal fluid or 200 microM l-trans-pyrrolidine-2,4-dicarboxilic acid with the chip. These results demonstrate the ability of this chip to sample and monitor chemicals in the complex environment of the central nervous system with high selectivity and sensitivity over extended periods.     

New directions in single polymer dynamics

Single polymer techniques are a powerful set of molecular-level tools that enable the direct observation of polymer chain dynamics under highly non-equilibrium conditions. In this way, single polymer methods have been used to uncover fundamentally new information regarding the static and dynamic properties of polymeric materials. However, to achieve the full potential of these new methods, single polymer techniques must be further advanced to enable the study of polymers with complex architectures, heterogeneous chemistries, flexible backbones, and intermolecular interactions in entangled solutions, which reaches far beyond the current state-of-the-art. In this article, we explore recent developments in the area of single polymer physics, including single molecule force spectroscopy and fluorescence microscopy, and we further highlight exciting new directions in the field. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013