Abstract
Hydrogen sulfide (H2S) and human NAD(P)H:quinine oxidoreductase 1 (hNQO1) are potential cancer biomarkers and also vital participants in cellular redox homeostasis. Simultaneous detection of these two biomarkers would benefit the diagnostic precision of related cancers and could also help to investigate their crosstalk in response to oxidative stress. Despite this importance, fluorescent probes that can be activated by the dual action of H2S detection and hNQO1 activity have not been investigated. To this end, dual-biomarker-triggered fluorescent probes 1 and 2 were rationally constructed by installing two chemoselective triggering groups into one fluorophore. Probe 1 provides a small turn-on fluorescence response toward H2S but a much larger response to both H2S and hNQO1 in tandem. By contrast, fluorescence probe 2 is activated only in the presence of both H2S and hNQO1. Probe 2 exhibits a large fluorescence turn-on (>400 fold), high sensitivity, excellent selectivity as well as good biocompatibility, enabling the detection of both endogenous H2S and hNQO1 activity in living cells. Bioimaging results indicated that probe 2 could differentiate HT29 and HepG2 cancer cells from HCT116, FHC and HeLa cells owing to the existence of relatively high endogenous levels of both biomarkers. Expanded investigations using 2 revealed that cells could generate more endogenous H2S and hNQO1 upon exposure to exogenous hydrogen peroxide (H2O2), implying the synergistic antioxidant effects under conditions of cellular oxidative stress.
Highlights
Cancer, one of the most life-threating diseases, is characterized as uncontrolled growth and division of normal cells beyond their natural boundaries
Chang et al reported the dual-analyte detection of H2O2 and caspase 8 activity during acute in ammation in living mice.20a Similar strategies have been used for the successful dual-analyte detection of small molecules.20b–d we report the rational design and preparation of H2S and human NAD(P)H:quinine oxidoreductase 1 (hNQO1) dual-responsive uorescent probes 1 and 2, which were successfully utilized to differentiate cancer cells and reveal the synergistic antioxidant effects in response to the oxidative stress
Rational design of the dual-biomarker-triggered uorescence probes To enable the simultaneous detection of H2S and hNQO1, we installed two chemoselective trigger groups that respond to H2S and hNQO1, respectively, into one uorophore
Summary
One of the most life-threating diseases, is characterized as uncontrolled growth and division of normal cells beyond their natural boundaries. The mortality of cancer remains high, which is mainly due to metastasis of primary cancer tumors.[1] The early stages of cancer development carry the maximum potential for therapeutic interventions, and the survival rate of certain cancers can be signi cantly improved with early diagnosis and treatment.[2] Cancer biomarkers are endogenous molecules that are differentially expressed in cancer cells relative to their normal counterparts Altered levels of such biomarkers can be measured to establish a correlation with the disease process and are useful for cancer diagnosis and therapy.[3] the simultaneous detection of multiple biomarkers can signi cantly increase diagnostic accuracy.[4] Recent research has demonstrated that hydrogen sul de (H2S) and human NAD(P)H:quinine oxidoreductase 1
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