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Hydrogen sulfide (H2S) plays a significant role in the onset and progression of cancer. It has led to increased interest in its potential as a diagnostic tool owing to its overexpression in cancer. However, research into the anti-cancer activity of H2S, particularly its ability to promote apoptosis, is hindered by the lack of effective detection tools. To gain a comprehensive understanding of the targeted efficacy of H2S in promoting cancer cell apoptosis, we designed and synthesized a self-immolative near-infrared fluorescent diagnostic probe, named YH-NO2. The activation of this self-immolative reaction is dependent on the presence of nitroreductase (NTR) overexpressed in tumor cells. The design of YH-NO2 involves releasing fluorophores through the activated self-immolative reaction for detection, while simultaneously releasing H2S-loaded self-immolative spacers to promote cancer cell apoptosis. Consequently, YH-NO2 achieves a seamless integration of recognizing and promoting cancer cell apoptosis through its self-immolative structure. This dual function allows YH-NO2 to recognize NTR activity in cells under varying hypoxia levels and differentiate between normal cells and cancer cells using imaging technology. Notably, YH-NO2 exhibits remarkable stability in cellular environments, providing controlled and selective H2S release, thereby targeting the elimination of cancer cells through the promotion of apoptosis. Furthermore, in vivo experiments have demonstrated that YH-NO2 can accurately identify tumor tissue and effectively reduce its size by utilizing its apoptosis-promoting properties. These findings not only provide further evidence for the anti-cancer activity of H2S but also offer valuable tools for understanding the complex relationship between H2S and cancer. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) poses a severe threat to public health. Endoplasmic reticulum (ER) stress contributes significantly to DILI pathogenesis, with peroxynitrite (ONOO−) identified as a pivotal indicator. However, the temporal and spatial fluctuations of ONOO− associated with ER stress in the pathogenesis of DILI remain unclear. Herein, a novel ER-specific near-infrared (NIR) probe (QM-ONOO) with aggregation-induced emission (AIE) features for monitoring ONOO− fluctuations in DILI was elaborately constructed. QM-ONOO exhibited excellent ER-targeting specificity, a large Stoke's shift, and a low detection limit (26.9 nM) toward ONOO−. QM-ONOO performed well in imaging both exogenous and endogenous ONOO− in HepG2 cells. Furthermore, molecular docking calculations validated the ER-targeting mechanism of QM-ONOO. Most importantly, using this probe allowed us to intuitively observe the dynamic fluctuations of ONOO− during the formation and remediation processes of DILI in the acetaminophen (APAP)-induced mouse model. Consequently, this work provides a promising tool for in-depth research of ONOO− associated pathological processes in DILI. [Display omitted] • An endoplasmic reticulum-targeted NIR fluorescent probe with aggregation-induced emission features was developed for ONOO−. • The multifunctional probe can detect ONOO− selectively and sensitively with fluorescence changes at 620 nm. • The fluorescence probe can image ER-associated ONOO− with low biotoxicity in cells. • The probe can monitor the fluctuations of ONOO− in the APAP-induced mouse model of DILI. [ABSTRACT FROM AUTHOR]

During biological detection, the toxicity caused by probes to living organisms is neglected. In this study, an analyte-compensated fluorescent probe (NP-SN3) was constructed for the detection of H2S. Through experiments with HepG2 cells and zebrafish embryos and larvae, the NP-SN3 probe showed no significant difference in imaging performance compared with the traditional probe (NP-N3) but exhibited lower detection-induced toxicity in the imaging of liver fibrosis in activated HSC-T6 cells. During the development of zebrafish embryos and continuous administration in rats, NP-SN3 showed a lower death rate, higher hatchability and lower malformation in zebrafish embryos and milder pathological symptoms in stained rat tissues. [ABSTRACT FROM AUTHOR]

Acid phosphatase has become a significant indicator of prognostic and medical diagnosis, and its dysfunction may lead to a series of diseases. A novel dual-signal fluorescence method for acid phosphatase detection based on europium polymer (europium-pyridine dicarboxylicacid-adenine) and pyridoxal phosphate (PLP) was proposed. PLP coordinated with europium polymer via Eu3+ and P–O bonds, and the fluorescence of europium polymer was quenched due to the photoinduced electron transfer (PET) effect between aldehyde and europium polymer. Upon addition of acid phosphatase, the PLP was transformed to phosphate (Pi) and pyridoxal (PL). The PL was released from the surface of europium polymer, and the blue emission was enhanced due to the formation of internal hemiacetal, while the fluorescence of europium polymer recovered. The blue (PL) and red emission (Eu3+) were positively correlated with acid phosphatase activity; thus the sensitive assay of acid phosphatase was effectively achieved. The two signals were applied to determine the acid phosphatase with limits of detection (LOD) of 0.04 mU/mL and 0.38 mU/mL, and the linear ranges were 0.13–5.00 mU/mL and 1.25–20.00 mU/mL, respectively. The probe can be used to trace the acid phosphatase in biological systems and holds promise for use in clinical diagnosis and early prevention. [ABSTRACT FROM AUTHOR]

As chloride ions (Cl−) play a vital role in maintaining normal physiological activity, detection of chloride ions is quite urgent. Hence, we developed chloride fluorescence probes to highly selectively and sensitively monitor chloride ions. The probe M2 with single emission has a high fluorescence quantum yield (Φ = 45%), and it is capable of quantitative detection of Cl− under physiological conditions (pH = 7.4) and pH = 5.0 with a linear range of 0.1-4.0 mM; nevertheless, it is of the switch-off type. We further synthesized a ratiometric fluorescent probe MY with M2 as raw material, which featured excellent selectivity and anti-interference, and large two-photon cross section (555 GM). The probe is conveniently used to detect Cl− in water samples and biological samples including human sweat, serum, and urine samples, indicating it holds great promise for chloride detection and biological application.ᅟ [ABSTRACT FROM AUTHOR]

We have prepared a near-infrared (NIR) turn-on fluorescent probe (NFC) based on chloroacetate modified naphthofluorescein for specific detection of cysteine (Cys) and homocysteine (Hcy) over glutathione (GSH) and other amino acids (AAs) with the detection limits of 0.30 μM and 0.42 μM, respectively. The fluorescence intensity of the naphthofluorescein (NF) chromophore is modulated by an internal charge transfer (ICT) process. The probe NFC is readily available and weakly fluorescent, but of observably enhanced fluorescence after reacting with Cys or Hcy. We assumed and then demonstrated that the fluorescence off–on process involves a conjugate nucleophilic substitution/cyclization sequence. Furthermore, the probe has been successfully applied for detecting the total content of Cys and Hcy in human plasma and imaging in living cells with low toxicity. [ABSTRACT FROM AUTHOR]

With increasing interest in optical in vivo imaging, there is a corresponding increase in demand for near-infrared (NIR) dyes. Such probes can be used, for example, to detect intracellular GSH, which would be helpful for understanding the mechanisms of diseases. In this work, we report a cyanine-based fluorescent probe that undergoes biothiol-promoted specific O-S cleavage and subsequent self-immolation through intramolecular 1,6-elimination. In addition, we investigated the cell viability of the system and successfully applied the probe to living cells, in vivo, and in various tissues. [ABSTRACT FROM AUTHOR]

This paper reported a facile method for fabricating a functionalized fluorescent graphene oxide (GO) by covalently grafting the amine-modified mesoporous silica nanoparticles (MSNs) containing poly(p-phenylenevinylene) (PPV) and lactam of Rhodamine 6G (SRh6G) inside the channel of MSNs. The resulted GO-PPV@MSN-NH 2 @SRh6G fluorescent hybrid nanoparticles had a good dispersion and strong green fluorescence in aqueous solution. This hybrid material can be used as a fluorescent ratiometric probe to detect Hg 2+ in the water through fluorescence resonance energy transfer (FRET). Upon the addition of only Hg 2+ ions, the mission corresponding to the ring-opened form of rhodamine appeared at 550 nm with a simultaneous emission quenching of PPV at 494 nm. This ratiometric fluorescence change indicated that an FRET from the PPV to rhodamine was triggered by Hg 2+ ions. The hybrid nanoparticles of GO-PPV@MSN-NH 2 @SRh6G could be used as a novel fluorescent probe to carry out the quantitative detection of Hg 2+ with a detection limit of 7.1 × 10 −8 M. [ABSTRACT FROM AUTHOR]

An uncontrolled increase of nitrite concentration in groundwater, rivers and lakes is a growing threat to public health and environment. It is important to monitor the nitrite levels in water and clinical diagnosis. Herein, we developed a switch-off fluorescence probe (PyI) for the sensitive detection of nitrite ions in the aqueous media. This probe selectively recognizes nitrite ions through a distinct visual color change from colorless to pink with a detection limit of 0.1 μM. This method has been successfully applied to the determination of nitrites in tap water, lake water and Yellow River water with recoveries in the range of 94.8%–105.4%. [ABSTRACT FROM AUTHOR]

The 4−N,N-dimethyl-1,8-naphthalimide based fluorescent probes have been explored for selective detection of Au 3+ . Both probes show a pronounced fluorescence enhancement response to Au 3+ . Hydroxy is introduced as ligand of Au 3+ for Probe 1 and the newly designed Probe 2 contains an alkyne moiety to recognize Au 3+ through an irreversible C≡C bond hydrolysis reaction. Probe 1 exhibits higher performance such as faster response, lower detection limit of 0.050 μM and the better responsive effect in 99.5% water system compared with most of probes published. The Probe 2 displays high stability to pH, suitable water solubility, wider linear range (0–100 μM) to Au 3+ , and live-cells imaging with low cytotoxicity. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) is a typical gas signal molecule that plays a vital role in various pathological courses. Despite having the accumulated knowledge on the physiological functions of H 2 S in many diseases, the process in the measurement of its level in mitochondria during oxidative stress is still far away from the expectation. In this regard, it is great significant to design a fluorescent probe for accurately monitoring the dynamics of H 2 S during oxidative stress. In this work, we firstly synthesized an oxidative stress activated fluorescence probe QM-RSH for tracking H 2 S level in mitochondria. It exhibited high selectivity and sensitivity for detecting H 2 S with lower limit of detection (LOD = 44.6 nM) in the presence of H 2 O 2. QM-RSH can be successfully applied to accurately monitor the fluctuation of H 2 S level during oxidative stress without interference from other physiological processes in living cells and zebrafish. Therefore, this multifunctional probe QM-RSH has great potential as an image tool in biological research. It also provides a novel strategy for designing fluorescent probe to investigate biomolecular information and signaling pathways under specific physiological conditions. [Display omitted] •A novel multifunction fluorescent probe QM-RSH was designed and synthesized. • QM-RSH can sequentially detect H 2 O 2 and H 2 S in two signal channels. • QM-RSH exhibited brighter NIR fluorescence and lower detection limit for H 2 O 2 (80.3 nM) and H 2 S (44.6 nM). • QM-RSH can be applied to accurately monitor H 2 S fluctuation during oxidative stress, avoiding interference from other physiological processes. • QM-RSH is used to investigate the main factors of H 2 S up-regulation during oxidative stress. [ABSTRACT FROM AUTHOR]

As a signal molecule involved in autophagy, hydrogen sulfide (H 2 S) is considered to be essential in the development and treatment of diseases. In order to clarify the complex role of H 2 S in organism and the participation of H 2 S in disease process, it is urgently needed to visualize the dynamics of H 2 S. In this contribution, a water-soluble near-infrared (695 nm emission) self-immolative fluorescent probe CySO 3 N 3 was constructed for H 2 S detection. The ability of self-immolative strategy to detect H 2 S was verified to increase the metabolic capacity and reduce the toxicity of probe. This probe can not only be used to detect H 2 S in living cell and mice, but also shows great potential in detecting H 2 S changes to monitor cell self-repair during inflammation and myocardial injury. [Display omitted] • A novel water-soluble near-infrared fluorescent probe CySO 3 N 3 was developed, which can detect H 2 S in PBS. • CySO 3 N 3 exhibits excellent biocompatibility, mitochondrial targeting ability and tissue penetration ability. • CySO 3 N 3 with a new self-immolative structure is less toxic. • CySO 3 N 3 is successfully applied to monitor the occurrence, self-repair and treatment of diseases in injury models. [ABSTRACT FROM AUTHOR]

N-quaternization of QOH could extend its emission from 555 nm to 720 nm and endow it mitochondrial targeting capabilities. The wavelength red-shift independent on the properties of substituent. QOH successfully be used to construct probe for detecting H 2 S (Q-SH) with "Turn-on" signal and H 2 O 2 (QM-R) with ratio fluorescence in vitro and in vivo. [Display omitted] • A novel fluorophore QOH was designed and synthesized. • N-quaternization of QOH could extend emission wavelength to NIR (720 nm) with a large Stokes shift (120 nm). • The wavelength red-shift independent on the properties of N-substituent. • –OH and N atom of QOH were used to construct probe for detecting H 2 S (Q-SH) and H 2 O 2 (QM-R) in vitro and in vivo. This is great significant to establish a method that extends the small molecules fluorescence emission wavelength to the near-infrared region (NIR) for in vivo imaging. Hence, we firstly reported a novel fluorogenic scaffold QOH that could extend its fluorescence wavelength from (λ em = 555 nm) to NIR (λ em = 720 nm) with a large Stokes shift (120 nm) by forming its N-quaternization product (QMOH). In addition, the effect of the introduction of substituent at different modification sites and the properties of substituent on the optical properties of QOH were fully discussed by theoretical calculation. To investigate the possibility of QOH as probe construction, the compound Q-SH and QM-R were synthesized and applied to detect H 2 S and H 2 O 2 in vitro and in vivo, respectively. This study provided an efficient strategy to extend fluorescence emission to NIR and design fluorescence probes with large ratio variation for accurately imaging biomarkers in biological system. [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HOCl), mainly generated in mitochondria, plays a critical role in various physiological processes. To better understand the role and function of HOCl in mitochondria, herein, we present the design and synthesis of a Mito-QL reporter for probing the HOCl within mitochondria without other interference generated in living cells. Through the combination of TICT/ICT mechanisms, probe Mito-QL , with large stokes shift (203 nm) and low background fluorescence, exhibited excellent sensitivity (900-fold fluorescence enhancement) and selectivity towards HOCl (LOD = 2.4 nM). The co-location experiments confirmed that probe Mito-QL can firstly localize in the mitochondria and then react with HOCl in mitochondria. Also, the probe is capable of imaging endogenous and exogenous HOCl even the generation of HOCl during the ferroptosis of cells, which is beneficial for more efficient application in biological imaging. [Display omitted] • The Mito-QL exhibited large Stokes shift (203 nm) and low detection limit (2.4 nM) for HOCl. • The Mito-QL could first target the mitochondria then accurately detect HOCl in mitochondria. • The Mito-QL was utilized to visualize the exogenous/endogenous HOCl in different cells, and the generation of HOCl during the ferroptosis of cells. [ABSTRACT FROM AUTHOR]

Understanding the complex relationship between active small molecules is of great significance in various physiological processes. Herein, we present the design and synthesis of a sequential responsive Lysosome-Naphthalene imide-Azido (lyso-NP-N 3) reporter for probing the H 2 S and HOBr within organelle (lysosome) in living cells. Probe lyso-NP-N 3 exhibited high selectivity and sensitivity towards H 2 S (LOD = 23.5 nM) and HOBr (LOD = 254 nM). Additionally, lyso-NP-N 3 possessed an excellent lysosome targeting ability and was utilized to visualize the exogenous/endogenous H 2 S and HOBr in RAW 264.7, Hela and HepG2 cells. Facilitated by this sequentially activated mechanism, the probe was successfully applied to confirm that the reported scavenger of HOBr, N-acetyl-L-cysteine (NAC) mainly relied on its metabolite H 2 S to eliminate excess HOBr, thereby playing the role of cell regulation and protection. These results establish the crosstalk between H 2 S and HOBr in lysosome and provide a promising tool to study metabolite interactions. [Display omitted] • A lysosome-targetable fluorescent probe lyso-NP-N 3 was developed for sensitive detection of H 2 S and HOBr sequentially. • The lyso-NP-N 3 was utilized to visualize the exogenous/endogenous H 2 S and HOBr in RAW 264.7, Hela and HepG2 cells. • It verified that N-acetyl-L-cysteine mainly relied on its metabolite H 2 S to eliminate excess HOBr. [ABSTRACT FROM AUTHOR]

Due to favourable efficiency and low cost, dual-response fluorescent probes play critical roles in the development of fluorescence assay system. Herein, a novel dual-response fluorescent probe (RDCN) was designed and synthesized for the detection of two environmental contaminants: hydrazine (N 2 H 4) and cyanide (CN−). Probe RDCN exhibited discriminative sensing behaviors to N 2 H 4 and CN− with different reaction mechanisms, allowing the high selectivity and sensitivity detection for N 2 H 4 and CN−. The probe itself displayed red-emitting fluorescence as a result of strong intramolecular charge transfer (ICT) between diethylamino and dicyano. After mixing with hydrazine, a new corresponding hydrazone came into being with an intense yellow fluorescence. While, the probe could also largely switch to blue fluorescence in response to CN−. Furthermore, the probe RDCN was successfully employed to determine N 2 H 4 and CN− in water samples with the detection limits of 0.08 μM and 0.33 μM, and to visualize N 2 H 4 and CN− in live cells by means of different fluorescence channels (blue and yellow channels), revealing that probe RDCN has potential applications for discriminative detection N 2 H 4 and CN− in biological environment. Image 1 • A dual-response fluorescent probe RDCN was developed for detection of hydrazine and cyanide. • Probe RDCN displayed significantly discriminative fluorescence signal towards hydrazine (red) and cyanide (yellow) based on different reaction mechanisms. • Probe RDCN could respectively and sensitively determine hydrazine (DL = 0.08 μM) and cyanide (DL = 0.33 μM). • The probe RDCN was successfully applied for imaging hydrazine and cyanide in living cells. [ABSTRACT FROM AUTHOR]