Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A self-immobilizing near-infrared fluorogenic probe for sensitive imaging of extracellular enzyme activity in vivo.

ABSTRACT: Reported herein is a self-immobilizing near-infrared fluorogenic probe that can be used to image extracellular enzyme activity in vivo. Using a fluorophore as a quinone methide precursor, this probe covalently anchors at sites of activation and greatly enhances the fluorescence intensity at 710 nm upon enzymatic stimulus, significantly boosting detection sensitivity in a highly dynamic in vivo system.

SUBMITTER: Li Y

PROVIDER: S-EPMC7449546 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A self-immobilizing near-infrared fluorogenic probe for sensitive imaging of extracellular enzyme activity in vivo.

Li Yuyao Y Song Heng H Xue Chenghong C Fang Zhijun Z Xiong Liqin L Xie Hexin H

Chemical science 20200513 23

Reported herein is a self-immobilizing near-infrared fluorogenic probe that can be used to image extracellular enzyme activity in vivo. Using a fluorophore as a quinone methide precursor, this probe covalently anchors at sites of activation and greatly enhances the fluorescence intensity at 710 nm upon enzymatic stimulus, significantly boosting detection sensitivity in a highly dynamic in vivo system. ...[more]

PMID: 32874510

Similar Datasets

Enzyme-activated near-infrared fluorogenic probe with high-efficiency intrahepatic targeting ability for visualization of drug-induced liver injury.

Project description:Hepatotoxicity is a serious problem faced by thousands of clinical drugs, and drug-induced liver injury (DILI) caused by chronic administration or overdose has become a major biosafety issue. However, the near-infrared (NIR) fluorescent probes currently used for liver injury detection still suffer from poor liver targeting ability and low sensitivity. Enzyme-activated fluorogenic probes with powerful in situ targeting ability are the key to improving the imaging effect of liver injury. Herein, we rationally designed a leucine aminopeptidase (LAP) activated fluorogenic probe hCy-CA-LAP, which greatly improved the hepatocyte-targeting capability by introducing a cholic acid group. The probe hCy-CA-LAP is converted into a high-emission hCy-CA fluorophore in the presence of LAP, showing high selectivity, high sensitivity and low detection limit (0.0067 U mL-1) for LAP, and successfully realizes the sensitive detection of small fluctuations of LAP in living cells. Moreover, the probe can achieve effective in situ accumulation in the liver, thereby achieving precise imaging and evaluation of two different types of drug-induced hepatotoxicity in vivo. Therefore, the probe hCy-CA-LAP may be a potential tool for exploring the roles of LAP and evaluating the degree of DILI.

| S-EPMC8597858 | biostudies-literature

Rapid differentiation between bacterial infections and cancer using a near-infrared fluorogenic probe.

Project description:The reliable differentiation between bacterial infections and other pathologies is crucial for both diagnostics and therapeutic approaches. To accommodate such needs, we herein report the development of an activatable near-infrared fluorescent probe 1 that could be applied in the ultrafast, ultrasensitive and specific detection of nitroreductase (NTR) activity in bacterial pathogens both in vitro and in vivo. Upon reaction with NTR, the nitro-group of the para-nitro phenyl sulfonic moiety present in probe 1 was reduced to an amino-group, resulting in a near-infrared fluorescence turn-on of the latent cyanine 7 fluorophore. Probe 1 was capable of rapid and real-time quantitative detection of 0-150 ng mL-1 NTR with a limit of detection as low as 0.67 ng mL-1 in vitro. In addition, probe 1 exhibited an outstanding performance of ultrafast measurements and suitable selectivity toward NTR to accurately sense intracellular basal NTR in ESKAPE bacterial pathogens. Most remarkably, probe 1 was capable of noninvasively identifying bacterial infection sites without showing any significantly increased signal of tumour sites in the same animal within 30 min.

| S-EPMC8157330 | biostudies-literature

A Near-Infrared Fluorogenic Pyrrole-Imidazole Polyamide Probe for Live-Cell Imaging of Telomeres.

Project description:Telomeres are closely associated with cellular senescence and cancer. Although some techniques have been developed to label telomeres in living cells for study of telomere dynamics, few biocompatible near-infrared probes based on synthetic molecules have been reported. In this study, we developed a near-infrared fluorogenic pyrrole-imidazole polyamide probe (SiR-TTet59B) to visualize telomeres by conjugating a silicon-rhodamine (SiR) fluorophore with a tandem tetramer pyrrole-imidazole polyamide targeting 24 bp in the telomeric double-stranded (ds) DNA. SiR-TTet59B was almost nonfluorescent in water but increased its fluorescence dramatically on binding to telomeric dsDNA. Using a peptide-based delivery reagent, we demonstrated the specific and effective visualization of telomeres in living U2OS cells. Moreover, SiR-TTet59B could be used to observe the dynamic movements of telomeres during interphase and mitosis. This simple imaging method using a synthetic near-infrared probe could be a powerful tool for studies of telomeres and for diagnosis.

| S-EPMC7683039 | biostudies-literature

Norcyanine-Carbamates Are Versatile Near-Infrared Fluorogenic Probes.

Project description:Fluorogenic probes in the near-infrared (NIR) region have the potential to provide stimuli-dependent information in living organisms. Here, we describe a new class of fluorogenic probes based on the heptamethine cyanine scaffold, the most broadly used NIR chromophore. These compounds result from modification of heptamethine norcyanines with stimuli-responsive carbamate linkers. The resulting cyanine carbamates (CyBams) exhibit exceptional turn-ON ratios (∼170×) due to dual requirements for NIR emission: carbamate cleavage through 1,6-elimination and chromophore protonation. Illustrating their utility in complex in vivo settings, a γ-glutamate substituted CyBam was applied to imaging γ-glutamyl transpeptidase (GGT) activity in a metastatic model of ovarian cancer. Overall, CyBams have significant potential to extend the reach of fluorogenic strategies to intact tissue and live animal imaging applications.

| S-EPMC9310664 | biostudies-literature

Dual-functional, receptor-targeted fluorogenic probe for in vivo imaging of extracellular protease expressions.

Project description:Herein, we report a new type of in vivo fluorogenic probe that enables simultaneous and active targeting of overexpressed receptors, ?(V)?(3) integrins, and extracellular proteases, matrix metalloproteinases (MMPs), in the tumor regions. This c(RGDyK)-conjugated MMP fluorogenic probe efficiently targets the tumor regions with high retention time while maintaining receptor binding affinity and substrate activity. The probe minimizes nonspecific accumulation, thus demonstrating improved tumor-to-background signal ratio (T/N) in both ?(V)?(3) integrin- and MMP-overexpressing U87MG tumor-bearing mouse model. This strategy can be easily tuned for a wide array of applications targeting various receptors and extracellular proteases in vivo.

| S-EPMC3118575 | biostudies-literature

Imaging bacterial peptidoglycan with near-infrared fluorogenic azide probes.

Project description:Fluorescent probes designed for activation by bioorthogonal chemistry have enabled the visualization of biomolecules in living systems. Such activatable probes with near-infrared (NIR) emission would be ideal for in vivo imaging but have proven difficult to engineer. We present the development of NIR fluorogenic azide probes based on the Si-rhodamine scaffold that undergo a fluorescence enhancement of up to 48-fold upon reaction with terminal or strained alkynes. We used the probes for mammalian cell surface imaging and, in conjunction with a new class of cyclooctyne D-amino acids, for visualization of bacterial peptidoglycan without the need to wash away unreacted probe.

| S-EPMC3992625 | biostudies-literature

Near-Infrared Fluorescent Probe for Sensitive Detection of Pb(II) Ions in Living Cells.

Project description:A new near-infrared fluorescent probe (NIR-PbP) for sensitive detection of Pb(II) ions in solution and living cells has been rationally designed and synthesized. The NIR-PbP is inherently non-fluorescent and gains fluorescence in the presence Pb(II) ions. The ion detection is based on Pb(II)-induced unmasking the fluorophore through the opening of the spyrocycle, with more than 500-fold fluorescence for sub-micromolar Pb(II) concentration. The NIR-PbP has high sensitivity, good photo-stability, low detection limit, and reversible response to Pb(II) ions.

| S-EPMC6162053 | biostudies-literature

Non-invasive imaging of tumors by monitoring autotaxin activity using an enzyme-activated near-infrared fluorogenic substrate.

Project description:Autotaxin (ATX), an autocrine motility factor that is highly upregulated in metastatic cancer, is a lysophospholipase D enzyme that produces the lipid second messenger lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Dysregulation of the lysolipid signaling pathway is central to the pathophysiology of numerous cancers, idiopathic pulmonary fibrosis, rheumatoid arthritis, and other inflammatory diseases. Consequently, the ATX/LPA pathway has emerged as an important source of biomarkers and therapeutic targets. Herein we describe development and validation of a fluorogenic analog of LPC (AR-2) that enables visualization of ATX activity in vivo. AR-2 exhibits minimal fluorescence until it is activated by ATX, which substantially increases fluorescence in the near-infrared (NIR) region, the optimal spectral window for in vivo imaging. In mice with orthotopic ATX-expressing breast cancer tumors, ATX activated AR-2 fluorescence. Administration of AR-2 to tumor-bearing mice showed high fluorescence in the tumor and low fluorescence in most healthy tissues with tumor fluorescence correlated with ATX levels. Pretreatment of mice with an ATX inhibitor selectively decreased fluorescence in the tumor. Together these data suggest that fluorescence directly correlates with ATX activity and its tissue expression. The data show that AR-2 is a non-invasive and selective tool that enables visualization and quantitation of ATX-expressing tumors and monitoring ATX activity in vivo.

| S-EPMC3835791 | biostudies-literature

Optical imaging of ovarian cancer using a matrix metalloproteinase-3-sensitive near-infrared fluorescent probe.

Project description:Epithelial ovarian cancer (EOC) is the seventh most common cancer among women worldwide. The 5-year survival rate for women with EOC is only 30%-50%, which is largely due to the typically late diagnosis of this condition. EOC is difficult to detect in its early stage because of its asymptomatic nature. Recently, near-infrared fluorescent (NIRF) imaging has been developed as a potential tool for detecting EOC at the molecular level. In this study, a NIRF-sensitive probe was designed to detect matrix metalloproteinase (MMP) activity in ovarian cancer cells. A cyanine fluorochrome was conjugated to the amino terminus of a peptide substrate with enzymatic specificity for MMP-3. To analyze the novel MMP-3 probe, an in vivo EOC model was established by subcutaneously implanting SKOV3 cells, a serous-type EOC cell line, in mice. This novel MMP-3-sensitive probe specifically reacted with only the active MMP-3 enzyme, resulting in a significantly enhanced NIRF emission intensity. Histological analysis demonstrated that MMP-3 expression and activity were enhanced in the stromal cells surrounding the ovarian cancer cells. These studies establish a molecular imaging reporter for diagnosing early-stage EOC. Additional studies are required to confirm the early-stage activity of MMP-3 in EOC and its diagnostic and prognostic significance.

| S-EPMC5794152 | biostudies-literature

A novel near-infrared fluorescent probe for sensitive detection of β-galactosidase in living cells.

Project description:A novel near-infrared fluorescent probe for β-galactosidase has been developed based on a hemicyanine skeleton, which is conjugated with a d-galactose residue via a glycosidic bond. The probe serves as a substrate of β-galactosidase and displays rapid and sensitive turn-on fluorescent responses to β-galactosidase in aqueous solution. A 12.8-fold enhancement of fluorescence intensity at 703 nm was observed after incubation of 10 nM of β-galactosidase with 5 μM probe for 10 min. The probe can sensitively detect as little as 0.1 nM of β-galactosidase and shows linear responses to the enzyme concentration below 1.4 nM. The kinetic study showed that the probe has high binding affinity to β-galactosidase with Km = 3.6 μM. The probe was used to detect β-galactosidase in living cells by employing the premature cell senescence model. The probe exhibited strong fluorescent signals in senescent cells but not in normal cells, which demonstrates that the probe is able to detect the endogenous senescence-associated β-galactosidase in living cells.

| S-EPMC5455349 | biostudies-literature