Probe For Selective Imaging Research Articles

Real-Time Imaging of Endocytosis and Intracellular Trafficking of Semiconducting Polymer Dots.

Semiconducting polymer dots (Pdots) have shown great promise in biomedical applications, including biosensing, drug delivery, and live imaging of cells and biomolecules. Insight into the mechanism and regulation of cellular uptake and intracellular metabolism of Pdots is important for the development of superior Pdots-based theranostic nanoconjugates. Herein, we performed real-time imaging of endocytosis and intracellular trafficking of a type of fluorescent Pdots that showed excellent biocompatibility in various types of cells. The endocytic routes and kinetics of Pdots were differently regulated in distinct cell types. Following endocytosis, Pdots were transported in vesicles along microtubule and destined for lysosomes. Furthermore, our results revealed exosome-mediated extracellular release of Pdots and have tracked the dynamic process at the single particle level. These results provide new insight into the design of more effective and selective imaging probes as well as drug carriers.

Hexaphenylbenzene appended AIEE active FRET based fluorescent probe for selective imaging of Hg2+ ions in MCF-7 cell lines

Hexaphenylbenzene (HPB) appended rhodamine derivative 4 has been synthesized which exhibits aggregation-induced emission enhancement (AIEE) characteristics and forms fluorescent aggregates in mixed aqueous media. These aggregates show remarkable fluorescence resonance energy transfer (FRET) in the presence of Hg2+ ions among various metal ions tested. Further these aggregates were also utilized for the ratiometric imaging of Hg2+ ions in MCF-7 cell lines.

In silico study and biological evaluation of 99mTc-tricabonyl oxiracetam as a selective imaging probe for AMPA receptors

The non-invasive quantification of AMPA receptors (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) could become a prognostic marker for brain disorders. 99mTc-tricarbonyl oxiracetam complex was prepared as a novel probe for AMPA receptor targeting with radiolabeling yield >98% and showed stability of 12 h. Molecular modeling and docking studies of 99mTc-tricarbonyl oxiracetam were performed. The results suggested that the complex act as very good positive allosteric modulators for AMPA receptor. The biodistribution studies revealed high brain uptake (7.5 ± 0.11% %ID/g) at 5 min post-I.V. injection that make 99mTc-tricarbonyl oxiracetam as a novel brain perfusion imaging radiotracer.

Carbazole-based two-photon fluorescent probe for selective imaging of mitochondrial hydrogen peroxide in living cells and tissues

The two-photon imaging in living cells and tissue demonstrated that the prepared probe possessed high specificity for mitochondrial H2O2.

A fluorescent switchable AIE probe for selective imaging of dipeptidyl peptidase-4 in vitro and in vivo and its application in screening DPP-4 inhibitors.

A novel fluorescent probe for in vitro and in vivo imaging of dipeptidyl peptidase-4 (DPP-4) was designed and synthesized. This probe is successfully utilized to screen DPP-4 inhibitors in living 3T3-L1 cells and zebrafish, which provides a novel approach for the discovery of anti-diabetes drugs.

Thrombin-mediated ratiometric two-photon fluorescent probe for selective imaging of endogenous ultratrace glutathione in platelet

Ultratrace change of reduced glutathione (GSH) can weaken coagulation function of platelet (PLT). Thus, rapid and sensitive imaging of GSH specific in PLT is beneficial for monitoring coagulation function of PLT. Many fluorescent probes for GSH have been reported, but ratio fluorescent probe with excellent two-photon property for screening PLT from peripheral blood and quantitative imaging of GSH are scarce. In this work, a thrombin-mediated two-photon GSH-specific fluorescent probe (IQDC-L) was reported. Sulfuric diamide, a key group as linker, was introduced into IQDC-L, which resulted in not only specific selectivity for GSH, but also FRET occurring in probe. When IQDC-L encountered GSH, “S–N” in sulfonamide group was cut off, and FRET was inhibited. Furthermore, fluorescence intensities at 520 and 595nm presented linear change on ratio mode in the range of GSH (2.0–65nM). The lowest detection for GSH was as low as 0.083nM. Intriguingly, IQDC-L under thrombin-mediated was able to screen PLT from peripheral blood without any interference. Thus, IQDC-L could be used to screen PLT from peripheral blood, and simultaneously, to in situ image ultratrace GSH.

99mTc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study

Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with 99mTc) with high in silico affinity. The novel prepared 99mTc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors. 99mTc-amitrole was radio-synthesized with a high radiochemical yield (89.7±3.25). It showed in vitro stability for up to 6h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60min post-injection. The data described previously could recommend 99mTc-amitrole as potential targeting scintigraphic probe for solid tumor imaging.

Water-soluble colorimetric and ratiometric fluorescent probe for selective imaging of palladium species in living cells.

A novel water-soluble colorimetric and ratiometric fluorescent probe was synthesized and applied to imaging palladium species under physiological conditions in phosphate buffered saline (PBS) containing less than 1% organic cosolvent without adding any additional reagents. Based on palladium triggered terminal propargyl ethers cleavage reaction, the probe exhibited a high selectivity and sensitivity for palladium species of all the typical oxidation states (0, +2, +4), with a low detection limit (25 nM, 2.7 μg/L) and an obvious color change. Furthermore, the probe was successfully used for ratiometric fluorescence imaging of palladium in living cells.

Shell‐Crosslinked Hyaluronic Acid Nanogels for Live Monitoring of Hyaluronidase Activity In Vivo

A hyaluronidase (HAdase) has been noticed as a potential drug target as well as prognostic marker because of its close associations with tumor invasion, metastasis, and angiogenesis. Accordingly, precise monitoring of HAdase activity in vivo seems to be crucial not only for the evaluation of HAdase activity but also for non-invasive molecular imaging. In our study, we propose a new organic, near-infrared fluorescence imaging probe, indocyanine green (ICG)-based stimuli-responsive fluorescence probe for selective imaging of HAdases with appreciable signal-to-noise (S/N) ratios in serum and in vivo. Shell-crosslinked hyaluronic acid (HA) nanogels (sc-nanogels) are generated via a reducible covalent linkage which incorporate ICG derivatives. The ICG-embeded HA nanogels via shell-crosslinking have preferable properties for ideal selective imaging and detection of HAdase activity in vivo. The sc-nanogels exhibit prominent chemical stability against external light, greatly control background signals in serum, and small size compared to use of self-assembled ICG-based carriers. Collapsed ICG in the hydrogel core is selectively disentangled by HAdase treatment for selective near-infrared imaging without unwanted background signal. The newly designed sc-nanogels may have great potential to serve as probes for improved selective imaging of HAdase-associated diseases in clinics as well as HAdase-activity screening in vivo.

Chemical Design of 99mTc-Labeled Probes for Targeting Osteogenic Bone Region

Radionuclide bone imaging using polynuclear (99m)Tc complexes of bisphosphonates is the most common clinical practice in nuclear medicine. However, the improvement in the contrast between normal and osteogenic bone regions has been required. Herein we reported a new (99m)Tc-labeled compound considering the increased vascular permeability of osteogenic region. We selected penta-d-Asp as both a targeting motif to hydroxyapatite (HA) and a molecular size modifier, and two penta-d-Asp molecules were conjugated with the two carboxylate residues of ethylene dicysteine (EC) selected as the (99m)Tc chelating moiety to prepare EC-[(d-Asp)5]2. The molecular size, HA binding, and pharmacokinetics of (99m)Tc-EC-[(d-Asp)5]2 in normal mice and model rats bearing osteogenic tumor were compared to those of (99m)Tc-MDP and (99m)Tc-EC with one (d-Asp)5 motif, (99m)Tc-EC-(d-Asp)5. The molecular size of (99m)Tc-EC-[(d-Asp)5]2 was higher than that of (99m)Tc-MDP and (99m)Tc-EC-(d-Asp)5 when determined by permeability of the (99m)Tc-compounds through a membrane filter (10 kDa). The HA binding of (99m)Tc-EC-[(d-Asp)5]2 was higher than and similar to that of (99m)Tc-EC-(d-Asp)5 and (99m)Tc-MDP. (99m)Tc-EC-[(d-Asp)5]2 exhibited significantly lower accumulation in normal bone of mice than did (99m)Tc-MDP. In osteogenic tumor bearing model rats, (99m)Tc-EC-[(d-Asp)5]2 accumulated in the osteogenic and normal bone region similar to and lower than (99m)Tc-MDP, respectively. Although further studies including the chain length of d-Asp are required, these findings indicated that the present chemical design of (99m)Tc-labeled probe would be applicable to develop (99m)Tc-labeled probes for selective imaging of osteogenic bone region as well as develop therapeutic agents using therapeutic radionuclides such as (90)Y, (177)Lu, (186)Re, or (188)Re and cytotoxic agents to osteogenic bone tumor region.

Folic Acid Functionalized Nanoprobes for Fluorescence‐, Dark‐Field‐, and Dual‐Imaging‐Based Selective Detection of Cancer Cells and Tissue

AbstractFolate‐functionalized quantum dots, gold/silver nanoparticles, and magnetic quantum dots have been synthesized and used as fluorescence, dark‐field, and dual‐imaging probes for the detection of cancer cells and tissues. A very efficient and generalized folate‐functionalization method has been developed for various amine‐terminated nanoparticles. The advantages of the presented approach are that it can be used to synthesize a wide range of folate‐functionalized nanoparticles and the number of folate molecules per nanoparticle can be controlled easily to tune their interaction with folate receptors present at the cell surface. These folate‐functionalized nanoparticles have been used as cellular and tissue‐imaging bioprobes. Results show that folate‐functionalized nanoparticles act as efficient and selective imaging probes in targeting cancer cells and tissues and labeled cells/tissues can be detected by using different imaging modalities.

A Reaction-Based Fluorescent Probe for Selective Imaging of Carbon Monoxide in Living Cells Using a Palladium-Mediated Carbonylation

Carbon monoxide is a member of the gasotransmitter family, which also includes NO and H(2)S, and has been implicated in a variety of pathological and physiological conditions. Whereas exogenous therapeutic additions of CO to tissues and whole animals have been well-studied, the real-time spatial and temporal tracking of CO at the cellular level remains an open challenge. Here we report a new type of turn-on fluorescent probe for selective CO detection based on palladium-mediated carbonylation reactivity. CO Probe 1 (COP-1) is capable of detecting CO both in aqueous buffer and in live cells with high selectivity over a range of biologically relevant reactive small molecules, providing a potentially powerful approach for interrogating its chemistry in biological systems.

Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque

Over the last several decades, basic cardiovascular research has significantly enhanced our understanding of pathobiological processes leading to formation, progression, and complications of atherosclerotic plaques. By harnessing these advances in cardiovascular biology, imaging has advanced beyond its traditional anatomical domains to a tool that permits probing of particular molecular structures to image cellular behaviour and metabolic pathways involved in atherosclerosis. From the nascent atherosclerotic plaque to the death of inflammatory cells, several potential molecular and micro-anatomical targets for imaging with particular selective imaging probes and with a variety of imaging modalities have emerged from preclinical and animal investigations. Yet, substantive barriers stand between experimental use and wide clinical application of these novel imaging strategies. Each of the imaging modalities described herein faces hurdles-for example, sensitivity, resolution, radiation exposure, reproducibility, availability, standardization, or costs. This review summarizes the published literature reporting on functional imaging of vascular inflammation in atherosclerotic plaques emphasizing those techniques that have the greatest and/or most immediate potential for broad application in clinical practice. The prospective evaluation of these techniques and standardization of protocols by multinational networks could serve to determine their added value in clinical practice and guide their development and deployment.

Reaction-Based Fluorescent Probes for Selective Imaging of Hydrogen Sulfide in Living Cells

Hydrogen sulfide (H(2)S) is emerging as an important mediator of human physiology and pathology but remains difficult to study, in large part because of the lack of methods for selective monitoring of this small signaling molecule in live biological specimens. We now report a pair of new reaction-based fluorescent probes for selective imaging of H(2)S in living cells that exploit the H(2)S-mediated reduction of azides to fluorescent amines. Sulfidefluor-1 (SF1) and Sulfidefluor-2 (SF2) respond to H(2)S by a turn-on fluorescence signal enhancement and display high selectivity for H(2)S over other biologically relevant reactive sulfur, oxygen, and nitrogen species. In addition, SF1 and SF2 can be used to detect H(2)S in both water and live cells, providing a potentially powerful approach for probing H(2)S chemistry in biological systems.