H2S produced in small amounts by mammalian cells has been identified in mediating biological signaling functions. However, the in situ trapping of endogenous H2S generation is still handicapped by a lack of straightforward methods with high selectivity and fast response. Here, we encapsulate a semi-cyanine-BODIPY hybrid dye (BODInD-Cl) and its complementary energy donor (BODIPY1) into the hydrophobic interior of an amphiphilic copolymer (mPEG-DSPE), especially for building up a ratiometric fluorescent H2S nanoprobe with extraordinarily fast response. A remarkable red-shift in the absorption band with a gap of 200 nm in the H2S response can efficiently switch off the Förster resonance energy transfer (FRET) from BODIPY1 to BODInD-Cl, subsequently recovering the donor fluorescence. Impressively, both the interior hydrophobicity of supramolecular micelles and electron-withdrawing nature of indolium unit in BODInD-Cl can sharply increase aromatic nucleophilic substitution with H2S. The ratiometric strategy based on the unique self-assembled micellar aggregate NanoBODIPY achieves an extremely fast response, enabling in situ imaging of endogenous H2S production and mapping its physiological and pathological consequences. Moreover, the amphiphilic copolymer renders the micellar assembly biocompatible and soluble in aqueous solution. The established FRET-switchable macromolecular envelope around BODInD-Cl and BODIPY1 enables cellular uptake, and makes a breakthrough in the trapping of endogenous H2S generation within raw264.7 macrophages upon stimulation with fluvastatin. This study manifests that cystathione γ-lyase (CSE) upregulation contributes to endogenous H2S generation in fluvastatin-stimulated macrophages, along with a correlation between CSE/H2S and activating Akt signaling pathway.
γ-Glutamyltranspeptidase (GGT) is a tumor biomarker that selectively catalyzes the cleavage of glutamate overexpressed on the plasma membrane of tumor cells. Here, we developed two novel fluorescent in situ targeting (FIST) probes that specifically target GGT in tumor cells, which comprise 1) a GGT-specific substrate unit (GSH), and 2) a boron-dipyrromethene (BODIPY) moiety for fluorescent signalling. In the presence of GGT, sulfur-substituted BODIPY was converted to amino-substituted BODIPY, resulting in dramatic fluorescence variations. By exploiting this enzyme-triggered photophysical property, we employed these FIST probes to monitor the GGT activity in living cells, which showed remarkable differentiation between ovarian cancer cells and normal cells. These probes represent two first-generation chemodosimeters featuring enzyme-mediated rapid, irreversible aromatic hydrocarbon transfer between the sulfur and nitrogen atoms accompanied by switching of photophysical properties.
By employing a dual response approach, distinguishable fluorescence signals are initiated by GSH-mediated and Cys/Hcy-induced cascade reactions, thus allowing selective detection.
A fluorescent probe for fulfilling a lysosome targeting function in hypoxic tumor cells is reported, wherein azoreductase triggers a dramatic fluorescence enhancement and specific imaging of lysosomes in hypoxic cancer cells.
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