Synthesis and characterization of fluorescent magneto polymeric nanoparticles (FMPNs) for bimodal imaging probes

Novel bifunctional fluorescent magneto polymeric nanoprobes (FMPNs) were synthesized to provide simultaneous diagnostic information via magnetic resonance imaging (MRI) and optical imaging. FMPNs consist of ultra-sensitive magnetic nanocrystals that function as MR probes combined with Nile Red, which functions as a fluorescent probe. FMPNs were encapsulated by a nano-emulsion method in polyvinyl alcohol (PVA, 87–89% hydrolyzed) through a matrix of polymethyl methacrylate (PMMA). FMPNs exhibited excellent colloidal stability and monodispersity. The production of MR and optical images demonstrated that FMPNs have potential as dual-mode imaging agents.     

Towards highly efficient,intelligent and bimodal imaging probes: Novel approaches provided by lanthanide coordination chemistry

Gd³⁺ complexes are widely used as contrast enhancing agents in medical magnetic resonance imaging (MRI). In recent years, new fields have emerged in their development. The general tendency of using higher magnetic fields in biomedical and clinical MRI for a better signal to noise ratio calls for new contrast agents specifically optimized for such high field applications. Molecular imaging, aiming at the non-invasive visualisation of expression and function of bioactive molecules, requires imaging probes that provide a specific magnetic response to a particular molecular event. Finally, bimodal imaging may allow for combining the excellent resolution of MRI with a good sensitivity of other imaging modalities, such as optical methods. It requires bimodal imaging probes that satisfy requirements for both modalities within a single molecule. Here we review our latest efforts to develop novel lanthanide-based contrast agents in these specific fields and demonstrate the possibilities offered by lanthanide coordination chemistry.     

Biomarker-targeted fluorescent probes for breast cancer imaging

This review summarized fluorescent probes for breast cancer imaging according to different biomarkers probes recognized.     

Reporter protein-targeted probes for magnetic resonance imaging

Contrast agents for magnetic resonance imaging are frequently employed as experimental and clinical probes. Drawbacks include low signal sensitivity, fast clearance, and nonspecificity that limit efficacy in experimental imaging. In order to create a bioresponsive MR contrast agent, a series of four Gd(III) complexes targeted to the HaloTag reporter were designed and synthesized. HaloTag is unique among reporter proteins for its specificity, versatility, and the covalent interaction between substrate and protein. In similar systems, these properties produce prolonged in vivo lifetimes and extended imaging opportunities for contrast agents, longer rotational correlation times, and increases in relaxivity (r(1)) upon binding to the HaloTag protein. In this work we report a new MR contrast probe, 2CHTGd, which forms a covalent bond with its target protein and results in a dramatic increase in sensitivity. A 6-fold increase in r(1), from 3.8 to 22 mM(-1) s(-1), is observed upon 2CHTGd binding to the target protein. This probe was designed for use with the HaloTag protein system which allows for a variety of substrates (specific for MRI, florescence, or protein purification applications) to be used with the same reporter.     

A heterobimetallic ruthenium-gadolinium complex as a potential agent for bimodal imaging

Trinuclear heterobimetallic Ln(III)-Ru(II) complexes (Ln = Eu, Gd) based on a 1,10-phenanthroline ligand bearing a diethylenetriaminepentaacetic acid (DTPA) core have been synthesized and fully characterized by a range of experimental techniques. The (17)O NMR and proton nuclear magnetic relaxation dispersion (NMRD) measurements of Gd(III)-Ru(II) show that, in comparison to the parent Gd-DTPA, this complex exhibits improved relaxivity, which is the result of an increase of the rotational correlation time. Relaxometry and ultrafiltration experiments indicate that the 1,10-phenanthroline ligand has a high affinity for noncovalent binding to human serum albumin, which results in a high relaxivity r(1) of 14.3 s(-1) mM(-1) at 20 MHz and 37 °C. Furthermore, the Ln(III)-Ru(II) complexes (Ln = Eu, Gd) show an intense light absorption in the visible spectral region due to metal-to-ligand charge transfer (MLCT) transitions. Upon excitation into the MLCT band at 440 nm, the complexes exhibit a bright-red luminescence centered at 610 nm, with a quantum yield of 4.7%. The luminescence lifetime equals 540 ns and is therefore long enough to exceed the fluorescent background. Monometallic lanthanide complexes have also been synthesized, and the Eu(III) analogue shows a characteristic red luminescence with a quantum yield of 0.8%. Taking into account the relaxometric and luminescent properties, the developed Gd(III)-Ru(II) complex can be considered as a potential in vitro bimodal imaging agent.     

Boronate-based fluorescent probes for imaging cellular hydrogen peroxide

The syntheses, properties, and biological applications of the Peroxysensor family, a new class of fluorescent probes for hydrogen peroxide, are presented. These reagents utilize a boronate deprotection mechanism to provide high selectivity and optical dynamic range for detecting H2O2 in aqueous solution over similar reactive oxygen species (ROS) including superoxide, nitric oxide, tert-butyl hydroperoxide, hypochlorite, singlet oxygen, ozone, and hydroxyl radical. Peroxyresorufin-1 (PR1), Peroxyfluor-1 (PF1), and Peroxyxanthone-1 (PX1) are first-generation probes that respond to H2O2 by an increase in red, green, and blue fluorescence, respectively. The boronate dyes are cell-permeable and can detect micromolar changes in H2O2 concentrations in living cells, including hippocampal neurons, using confocal microscopy and two-photon microscopy. The unique combination of ROS selectivity, membrane permeability, and a range of available excitation/emission colors establishes the potential value of PR1, PF1, PX1, and related probes for interrogating the physiology and pathology of cellular H2O2.     

AIEgen based light-up probes for live cell imaging

Fluorescent light-up probes comprising a tetraphenylethene unit with aggregation-induced emission (AIE) characteristics and a water-soluble peptide have been designed and synthesized which provide cell membrane and nuclear permeability to live cells. This strategy has offered new opportunities for the development of probes with light-up ability and good signal-to-noise ratio. The selectivity or targeting specificity is determined by the peptide sequence, i.e. a nuclear localization signal that leads to nucleus imaging and a cell biomarker targeting peptide that offers specific light-up imaging of HT-29 cells.     

Spectrally distinct near-infrared probes for multiplexed biomedical imaging

Our bodies contain a huge amount of anatomical,physiolo-gical,cellular or molecular information.The understanding of how these pieces of information are organiz...     

An aryl-phosphonate appended macrocyclic platform for lanthanide based bimodal imaging agents

Four ligand systems have been prepared whose characteristics are well suited to the design of bimodal MRI and luminescence probes. The lanthanide complexes display high relaxivities and luminescence quantum yields. These properties are retained at higher magnetic fields and in a range of competitive environments including model extracellular medium and cultured cells.     

Apoptosis imaging by radionuclide probes

Apoptosis has attracted more and more research interests due to the critical role it played in the human health. Also, it is often confused with other types of cell death. Thus, methods that enable sensitive detection and noninvasive visualized imaging of apoptosis will be of enormous benefit in the development of new diagnostics, therapies and patient management. During the past decades, with the development of apoptosis understanding and molecular imaging modalities, a large collection of imaging agents based on well-defined molecular markers and/or physiological features have been developed and tested in preclinical and clinical studies. In this review, we mainly discuss radionuclide imaging probes, ranging from simple attachments of reporter moieties to proteins and peptides, to rationally designed probes that allow multimodal imaging. Furthermore, we briefly outline the current status of clinical translation and attempt to give an outlook on the further study.     

分子影像探针

分子影像是近年出现并迅速发展的一个生物医学领域,在疾病的治疗与诊断中发挥着重要作用。同时它又是一门交叉学科,涉及化学、医学、生物、计算机科学、放射科学、材料科学等。分子影像的发展除了需要先进的成像设备外,最关键的是合成新型而高效的成像探针。目前,分子影像探针广泛应用于科学研究和临床,并且也取得了巨大进步。本文主要综述了5种常见的分子影像探针:超声成像探针、X-射线计算机断层成像探针、光学成像探针、核磁共振成像探针、正电子发射计算机断层扫描成像探针,并对分子影像探针的应用进行了概述,最后对分子影像探针的发展进行了展望。     

Luminescent probes for detection and imaging of hydrogen peroxide

The relevance of hydrogen peroxide (H₂O₂) in biological processes has been underestimated for a long time. In recent years, various reports showed that H₂O₂ not only acts as a cytotoxic compound appearing in the course of oxidative stress, but also functions as an important signaling molecule. Fluorescent probes (or indicators) and nanoparticles that respond selectively to hydrogen peroxide can be applied for intracellular measurements or in vivo imaging, and are superior to electrochemical methods, e.g. in terms of spatial resolution. In contrast to previous reviews that concentrated on the adoption of different probes for certain applications, this survey highlights the basic principles of different probes in terms of their chemical design, structures and functionalities. Thus, the probes are classified according to the underlying reaction mechanism: oxidation, hydrolysis, photoinduced electron transfer, and lanthanide complexation. Other assays are based on fluorescent proteins and nanoparticles, and chemi- or bioluminescent reagents. We confine this review to probes that display a more or less distinct selectivity to hydrogen peroxide. Indicators responding to reactive oxygen species (ROS) in general, or to particular other ROS, are not covered. Finally, we briefly discuss future trends and perspectives of these luminescent reporters in biomedical research and imaging.

Bodipy-diacrylate imaging probes for targeted proteins inside live cells

A bodipy probe was developed for site-specific labeling of tagged proteins inside live cells which displays a large spectral change upon covalent coupling to the designed peptide that contains two pairs of Arg-Cys.     

Recent development on peptide-based probes for multifunctional biomedical imaging

Peptide-based probes play prominent roles in biomedical research due to their promising properties such as high biocompatibility, fast excretion, favorable pharmacokinetics as well as easy and robust preparation. Considering the translation of imaging probes into clinical applications, peptide-based probes remain to be the most desirable and optimal candidates.     

Principles of responsive lanthanide-based luminescent probes for cellular imaging

The advent of chemical tools for cellular imaging—from organic dyes to green fluorescent proteins—has revolutionized the fields of molecular biology and biochemistry. Lanthanide-based probes are a new player in this area, as the last decade has seen the emergence of the first responsive luminescent lanthanide probes specifically intended for imaging cellular processes. The potential of these probes is still undervalued by the scientific community. Indeed, this class of probes offers several advantages over organic dyes and fluorescent proteins. Their very long luminescence lifetimes enable quantitative spatial determination of the intracellular concentration of an analyte through time-gating measurements. Their emission bands are very narrow and do not overlap, enabling the simultaneous use of multiple lanthanide probes to quantitatively detect several analytes without cross-interference. Herein we describe the principles behind the development of this class of probes. Sensors for a desired analyte can be designed by rationally manipulating the parameters that influence the luminescence of lanthanide complexes. We will discuss sensors based on varying the number of inner-sphere water molecules, the distance separating the antenna from the lanthanide ion, the energies of excited states of the antenna, and PeT switches.

Metabolic probes for imaging endosymbiotic bacteria within toxic dinoflagellates

Fluorescence microscopy offers an important tool for the study of complex biological phenomena such as symbiosis. Here we identify a strategy that adapts the unique differences between the secondary metabolism in host and guest symbiotic species to selectively image endosymbiotic organisms. The method is demonstrated by application to the complex symbiotic relationships in toxic marine dinoflagellates.