Abstract:Alkaline phosphatases are a group of enzymes that play important roles in regulating diverse cellular functions and disease pathogenesis. Hence, developing fluorescent probes for in vivo detection of alkaline phosphatase activity is highly desirable for studying the dynamic phosphorylation in living organisms. Here, we developed the very first reaction-based near-infrared (NIR) probe (DHXP) for sensitive detection of alkaline phosphatase activity both in vitro and in vivo. Our studies demonstrated that the pro… Show more
“…Forschungsartikel assessed in HeLa cells overproducing ALP. [19] Thec ells pretreated with or without sodium orthovanadate (Na 3 VO 4 ; ALP inhibitor [20] )w ere incubated with ALP PS for 30 minutes, followed by washing of the cells.Upon imaging,control cells pretreated with Na 3 VO 4 showed no detectable fluorescence, whereas the fluorescence of unpretreated cells was visible (see Figure S21). This observation should be ascribed to the endogenous ALP-triggered conversion of ALP PS into PS Se-I .…”
Activatable photosensitizers (aPSs) sensitive to specific stimuli hold potential for targeting multiple disease biomarkers and are desirable for photodynamic therapy (PDT). Presented herein is the design of aPSs that can be activated and fully recover from an inhibited state in the presence of specific biomarker. A designed long‐wavelength D‐π‐A photosensitizer, PSSe‐I, with highly efficient photosensitivity for generation of 1O2 was used. Caging of the phenolate donor of PSSe‐I with a biomarker‐sensitive group provided ALPPS, and the drastic activation of its photosensitivity was demonstrated intracellularly. To enhance the flexibility of the design strategy, a clickable azide group was introduced into the scaffold to allow integration of more functionality. Modularly derived mito‐PNPS, equipped with a mitochondria‐targeting group and a specific peroxynitrite‐reactive trigger, was synthesized and demonstrated superior performance in cells. This strategy could lead to customization of aPSs applicable to a specific PDT.
“…Forschungsartikel assessed in HeLa cells overproducing ALP. [19] Thec ells pretreated with or without sodium orthovanadate (Na 3 VO 4 ; ALP inhibitor [20] )w ere incubated with ALP PS for 30 minutes, followed by washing of the cells.Upon imaging,control cells pretreated with Na 3 VO 4 showed no detectable fluorescence, whereas the fluorescence of unpretreated cells was visible (see Figure S21). This observation should be ascribed to the endogenous ALP-triggered conversion of ALP PS into PS Se-I .…”
Activatable photosensitizers (aPSs) sensitive to specific stimuli hold potential for targeting multiple disease biomarkers and are desirable for photodynamic therapy (PDT). Presented herein is the design of aPSs that can be activated and fully recover from an inhibited state in the presence of specific biomarker. A designed long‐wavelength D‐π‐A photosensitizer, PSSe‐I, with highly efficient photosensitivity for generation of 1O2 was used. Caging of the phenolate donor of PSSe‐I with a biomarker‐sensitive group provided ALPPS, and the drastic activation of its photosensitivity was demonstrated intracellularly. To enhance the flexibility of the design strategy, a clickable azide group was introduced into the scaffold to allow integration of more functionality. Modularly derived mito‐PNPS, equipped with a mitochondria‐targeting group and a specific peroxynitrite‐reactive trigger, was synthesized and demonstrated superior performance in cells. This strategy could lead to customization of aPSs applicable to a specific PDT.
“…The fluorophore has demonstrated its suitability for fluorescence imaging of various biomolecules, such as the detection of β-Lactamase in Staphylococcus aureus 20 , the detection of nitroxyl (HNO) 21 and palladium 22 in live cells, the detection of nitroreductase 23 , γ-glutamyl transpeptidase 24 and tyrosinase 25 in zebrafish. More recently, the hemicyanine NIR dyes have been used for in vivo detection of cysteine 26,27 , alkaline phosphatase in tumor models 28–30 , superoxide radical anion 31 , hydrogen sulphide 32 , hydrogen polysulfides 33 and γ-glutamyl transpeptidase 34 in mice models.Figure 1Fluorescence detection of cellular senescence using the NIR-BG probe. λ ex = 680 nm; λ em = 708 nm.…”
Detection of cellular senescence is important not only in the study of senescence in various biological systems, but also in various practical applications such as image-guided surgical removal of senescent cells, as well as the monitoring of drug-responsiveness during cancer therapies. Due to the lack of suitable imaging probes for senescence detection, particularly in living subjects, we have developed an activatable near-infrared (NIR) molecular probe with far-red excitation, NIR emission, and high “turn-on” ratio upon senescence-associated β-galactosidase (SABG) activation. We present here the first successful demonstration of NIR imaging of DNA damage-induced senescence both in vitro and in human tumor xenograft models.
“…81 In contrast to the sedimentary nature of probe 36 , near-infrared probe 37 was designed for dynamic imaging of ALP in live mice. 14 Probe 38 , which targets PTP, is a two-photon acyloxymethyl ketone probe conjugated to cell-penetrating peptides to facilitate organelle-specific detection at tissue depths of up to 100 μm. 82 Far-red PTP probe 1 provides reduced phototoxicity and background autofluorescence along with enhanced cellular uptake compared to existing PTP probes.…”
Fluorogenic probes, small-molecule sensors that unmask brilliant fluorescence upon exposure to specific stimuli, are powerful tools for chemical biology. Those probes that respond to enzymatic catalysis illuminate the complex dynamics of biological processes at a level of spatiotemporal detail and sensitivity unmatched by other techniques. Here, we review recent advances in enzyme-activated fluorogenic probes for biological imaging. We organize our survey by enzyme classification, with emphasis on fluorophore masking strategies, modes of enzymatic activation, and the breadth of current and future applications. Key challenges such as probe selectivity and spectroscopic requirements are described alongside of therapeutic, diagnostic, and theranostic opportunities.
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