Search

A double 3D DNA walker nanomachine by DNAzyme self-driven positive feedback loop amplification for the detection of miRNA was constructed. This method uses two gold nanoparticles as the reaction core, and because of the spatial confinement effect the local concentration of the reactants increase the collision efficiency was greatly improved. Meanwhile, the introduction of positive feedback loop promotes the conversion efficiency. In presence of miRNA-21, a large amount of DNAzyme was released and hydrolyze the reporter probe, resulting the recovery of fluorescence signal. The linear range for miRNA-21 is 0.5–60 pmol/L, and the detection limit is 0.41 pmol/L (S/N = 3). This nanomachine has been successfully used for accurate detection of miRNA-21 expression levels in cell lysates. At the same time, it can enter cells for intracellular miRNA-21 fluorescence imaging, distinguishing tumor cells from normal cells. This combination of in vitro detection and imaging analysis of living cells can achieve the goal of jointly detecting cancer markers through multiple pathways, providing new ideas for early diagnosis and screening of diseases. A dual-core 3D DNA nanomachine based on DNAzyme positive feedback loop for highly sensitive MicroRNA imaging in living cells was constructed. [Display omitted] • A new double 3D DNA nanomachine uses the spatial confinement effect to improve the walking efficiency. • DNAzyme self-driven positive feedback loop amplification is introduced for sensitive analysis of miRNA. • This nanomachine was applied for the precise imaging of microRNA in living cells. [ABSTRACT FROM AUTHOR]

The in situ precise quantification and simultaneous imaging of low abundance microRNAs (miRNAs) within living cells is critical for cancer diagnosis, yet it remains a significant challenge. Leveraging the excellent sensitivity and spatiotemporal resolution of dark-field microscopy (DFM) and fluorescence imaging, we have successfully devised a novel detection approach using dual-signal reporter probes (DSRPs). These probes allow for highly sensitive detection of miRNA-21 in living cells via toehold-mediated strand displacement cascades. The DSRPs were constructed by Au nanoparticles and Ag nanoclusters core-satellite nanostructures. After the recognition of miRNA-21, the strand displacement cascades were triggered, inducing the disassembly of the Au/Ag core-satellite nanostructure with apparent scattering intensity decrease and peak wavelength shifts. Additionally, the fluorescence of Ag clusters could be recovered and further enhanced when in close proximity to specific guanine-rich strands. The dual-signal response capability enables the accurate detection of miRNA-21 from 1 fM to 1 nM, with a limit of detection reached 0.75 fM. DFM and fluorescent imaging of living cells efficiently confirms the applicable detection of miRNA-21 in complex detection media. The biosensor based on DSRPs represents a promising nanoplatform for visual monitoring and imaging of biomolecules in living cells, even at the single particle level. [Display omitted] • Dual-signal reporter probes was proposed based on core-satellite nanostructures. • Target microRNA triggered the strand displacement cascades on the probe surface. • The dual signals of LSPR shifts and fluorescence enhancement were induced. • Accurate detection and simultaneous imaging of intracellular microRNA were realized. [ABSTRACT FROM AUTHOR]

Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l -Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications. Tris-assisted one-step fabrication of functional F-CDs for specific folate receptor positive-expressed cancer cell imaging. [Display omitted] • F-CDs were fabricated via rich hydroxyl groups Tris to mediate hydrothermal process of FA and L-Arg. • Rich hydroxyl groups of Tris play a vital role in the optical properties and intrinsic targeting ability for FR positive-expressed cancer cell for labeling and tracking. • This study provides an efficient strategy to design fluorescent CDs for extensive applications. [ABSTRACT FROM AUTHOR]

Fluorescent sensors have been widely applied for biosensing, but probes for both multiple analytes sensing and photodynamic therapy (PDT) effect are less reported. In this article, we reported three AIE-based probes anchored with different mass-weight polyethylene glycol (PEG) tails, i.e., TPE-PEG160 , TPE-PEG350 , and TPE-PEG750 , for both adenosine-5′-triphosphate (ATP) and hydrogen sulfide (H 2 S) detection and also cancer cells photodynamic therapy. TPE-PEGn s (n = 160, 350 and 750) contain the tetraphenylethylene-based fluorophore core, the pyridinium and amide anion binding sites, the H 2 S cleavable disulfide bond, and the hydrophilic PEG chain. They exhibit a good amphiphilic property and can self-assemble nona-aggregation with a moderated red emission in an aqueous solution. Importantly, the size of aggregation, photophysical property, sensing ability and photosensitivity of these amphiphilic probes can be controlled by tuning the PEG chain length. Moreover, the selected probe TPE-PEG160 has been successfully used to detect environmental H 2 S and image ATP levels in living cells, and TPE-PEG750 has been used for photodynamic therapy of tumor cells under light irradiation. Three novel AIE-based probes TPE-PEGn s (n = 160, 350, 750) for both ATP and H 2 S detection and also cancer cells photodynamic therapy have been reported. [Display omitted] • Three novel AIE-based probes TPE-PEGn s (n = 160, 350, 750) were prepared. • TPE-PEGn s can detect ATP and H 2 S with a high sensitivity and selectivity. • Properties (size, optics, sensing) of TPE-PEGn s can be affected by PEG chain. • TPE-PEG160 can detect environmental H 2 S and image ATP in living cells. • TPE-PEG750 has been used for image-guided killing of cancer cells. [ABSTRACT FROM AUTHOR]

Determining the activity of lysosomal β-hexosaminidase in cells is of great importance for understanding the roles that these enzymes play in pathophysiological events. Herein, we designed the new fluorescent probe, βGalNAc-Rhod-CM(NEt 2), which consisted of a βGalNAc-linked rhodol unit serving as a β-hexosaminidase reactive fluorogenic moiety and a N,N′ -diethylaminocoumarin (CM(NEt 2)) group acting as a fluorescence marker for determining the degree of cell permeabilization. Treatment of βGalNAc-Rhod-CM(NEt 2) with β-hexosaminidase promoted generation of Rhod-CM(NEt 2), thereby leading to an increase in the intensity of fluorescence of Rhod. However, this probe did not respond to the functionally related glycosidase, O-GlcNAcase. The detection limit of βGalNAc-Rhod-CM(NEt 2) for β-hexosaminidase was determined to be 0.52 nM, indicating that it has high sensitivity for this enzyme. Furthermore, the probe functioned as an excellent fluorogenic substrate for β-hexosaminidase with k cat and K m values of 17 sec−1 and 22 μM, respectively. The results of cell studies using βGalNAc-Rhod-CM(NEt 2) showed that levels of β-hexosaminidase activity in cells can be determined by measuring the intensity of fluorescence arising from Rhod and that the intensity of fluorescence of CM(NEt 2) can be employed to determine the degree of cell permeabilization of the probe. Utilizing the new probe, we assessed β-hexosaminidase activities in several types of cells and evaluated the effect of glucose concentrations in culture media on the activity of this enzyme. [Display omitted] • Development of the sensitive and selective fluorescent probe for β-hexosaminidase. • Determination of levels of β-hexosaminidase activities in several types of cells. • Evaluation of effect of glucose concentrations in media on β-hexosaminidase activity. [ABSTRACT FROM AUTHOR]

This work presented a FRET-ICT based fluorescent probe (named NTC) composed of coumarin-benzothiazole as the acceptor and 4-nitrobenzo[ c ][1,2,5] oxadiazole (NBD) as the donor for the detection of SO 2 derivatives in NIR. Probe NTC possessed superior performance including selectivity, quickly response toward SO 3 2−/HSO 3 − and high energy transfer efficiency (94 %). The test strips provided a simple and effective tool in detecting the presence of bisulfite. Besides, NTC was applied to test the sulfur dioxide derivatives in food samples and cells. [Display omitted] • A NIR ratiometric fluorescent probe NTC was developed to detect sulfur dioxide derivatives. • NTC had a large Stokes shift of 150 nm and 94 % energy transfer efficiency. • NTC possessed good selectivity and sensitivity toward sulfur dioxide derivatives. • NTC was applied to detect sulfur dioxide derivatives in test strips, food samples and cell imaging. [ABSTRACT FROM AUTHOR]

Herein we developed a cascade detection mode for the detection of HS− and ClO− by the novel probe NM-Cl bearing a conjugating naphthalene-dicyanoisophorone unit. The probe displayed sensitive and remarkable fluorescent enhancement in response to HS−, but not to other analytes. The mixture of probe and HS− constructed a specific sensing system for ClO− by fluorescent quenching response. The mechanism studies indicated that the successive reacting of HS− substitution Cl atom in probe and then addition of ClO− facilitation a thiofuran ring-forming induced differentiated fluorescence emission. This study provides a novel mechanism for the detection of HS− and ClO−, the imaging of cell and living animal further indicating the good application prospects of the probe in biosensing and bioimaging. A highly specific and visible method for cascade detection HS− and ClO−. The substitution reaction of the Cl atom by SH group facilitates sensitive detection toward HS−. The responsiveness to ClO− is based on the thiofuran ring-forming reaction, which providing a brand-new mechanism for sensing ClO−. This cell and living animal imaging indicating the good application prospects of these probes in biosensing and bioimaging. [Display omitted] • A novel fluorescent probe for cascade detection of HS− and ClO− was developed. • The responsiveness to ClO− is based on the thiofuran ring-forming reaction, which provides a band-new mechanism for sensing ClO−. • The application of the probe in living cells and mice imaging reveal its potential for HS− and ClO− sensing. [ABSTRACT FROM AUTHOR]

The liver plays a crucial role in several important processes in the human body, including metabolism, detoxification, and immune function. When the liver experiences acute injury, it can cause significant harm and requires prompt detection. Traditional biomarkers lack specificity and cannot detect changes in real-time, making them unsuitable for monitoring pathological processes. Recent studies have shown that acute liver injury (ALI) is closely related to oxidative stress, with peroxynitrite (ONOO−) being a vital byproduct of liver metabolism and become a critical biomarker for detecting liver damage. As a result, this research developed an activatable near-infrared fluorescent probe W-3a that can be used to detect endogenous ONOO− in a mouse model of ALI induced by lipopolysaccharides (LPS). The probe has high selectivity and anti-interference ability, with a reaction time <10 min and a detection limit of 85 nM. It was successfully utilized in detecting endogenous ONOO− in cells and live imaging of ALI mice. This research developed an activatable near-infrared fluorescent probe W-3a that can be used to detect endogenous ONOO− in a mouse model of ALI induced by lipopolysaccharides (LPS). The probe has high selectivity and anti-interference ability, with a reaction time <10 min and a detection limit of 85 nM. It was successfully utilized in detecting endogenous ONOO− in cells and live imaging of ALI mice. [Display omitted] • Development of a near-infrared fluorescent probe W-3a. • W-3a has high sensitivity and selectivity for ONOO−. • Realized in vivo imaging of cells and liver-injured mice. [ABSTRACT FROM AUTHOR]

In most biophysiological processes, sulfur dioxide (SO 2) is an important intracellular signaling molecule that plays an important role. The change of SO 2 in cells are closely related to various diseases such as neurological disorders and lung cancer, so it is necessary to develop fluorescent probes with the ability to accurately detect SO 2 during physiological processes. In this work, we designed and synthesized a multifunctional fluorescent probe TIS. TIS has excellent properties such as near-infrared emission, large stokes shift, excellent SO 2 detection capabilities, low detection limit, high specificity and visualization of color change before and after reaction. Simultaneously, TIS has low cytotoxicity, good biocompatibility, clear cell imaging capability and mitochondrial targeting ability. In addition, the ability of TIS to be applied to different material surfaces for latent fingerprint fluorescence imaging was also explored. TIS provides an excellent method for the accurate detection of SO 2 derivatives and shows great potential applications in near-infrared cellular imaging and latent fingerprint fluorescence imaging. (a) TIS response mechanisms for HSO 3 −. (b) application of TIS. [Display omitted] • A NIR emission fluorescent probe with AIE characterization. • TIS has long emission wavelength (795 nm) and large Stokes shift (265 nm). • Dual detection channel for SO 2 derivatives accurate detection. • Superior colocalization effect on mitochondrial (0.86). • Clear three-level finger imaging capability. [ABSTRACT FROM AUTHOR]

Hypochlorite/hypochlorous acid (ClO−/HOCl) is a biologically crucial reactive oxygen species (ROS), produced in living organisms and has a critical role as an antimicrobial agent in the natural defense system. However, when ClO− is produced excessively, it can lead to the oxidative damage of biomolecules, resulting in organ damage and various diseases. Therefore, it is imperative to have a straightforward, quick and reliable method for over watching the minimum amount of ClO− in different environments. Herein, a new probe TTM , containing thienothiophene and malononitrile units, was developed for exceptionally selective and sensitive hypochlorite (ClO−) detection. TTM demonstrated a rapid "turn-on" fluorescence response (<30 s), naked-eye detection (colorimetric), voltammetric read-out with anodic scan, low detection limit (LOD = 0.58 μM and 1.43 μM for optical and electrochemical methods, respectively) and applicability in detecting ClO− in real water samples and living cells. This study represents one of the rare examples of a small thienothiophene-based molecule for both optical and electrochemical detections of ClO− in an aqueous medium. [Display omitted] [ABSTRACT FROM AUTHOR]

Logic gate-based fluorescent probes are powerful tools for the discriminative sensing of multiple signaling molecules that are expressed in concert during the progression of many diseases such as inflammation, cancer, aging, and other disorders. To achieve logical sensing, multiple functional groups are introduced to the different substitution sites of a single fluorescent dye, which increases the complexity of chemical synthesis. Herein, we report a simple strategy that incorporates just one responsive unit into a hemicyanine dye achieving the logic gate-based sensing of two independent analytes. We introduce boronic acid to hemicyanine to quench the fluorescence, and in the presence of hydrogen peroxide (H 2 O 2), the fluorescence is recovered due to removal of the boronate. Interestingly, the subsequent decrease in pH turned the red fluorescence of hemicyanine to green emissive because of protonation of the phenolic alcohol. This unique feature of the probe enables us to construct "INHIBIT" and "AND" logical gates for the accurate measuring of intracellular H 2 O 2 and acidic pH in tandem. This study offers insight into the simple construction of logic-gate based fluorescent probes for the tandem sensing of multiple analytes that are correlatively produced during disease progression. Logical probes HCyBA for tandem sensing of H 2 O 2 and pH by using of just one reactive unit and the construction of logic gates for diagnosis of H 2 O 2 and acid related pathological cells are reported. [Display omitted] • A general strategy to develop logic gate-based fluorescent probes for tandem sensing of H 2 O 2 and acidic pH. • Red fluorescence of the probe is activated in the presence of H 2 O 2 , and then turned green when pH decreases. • Construction of "INHIBIT" and "AND" logic gates for precise sensing of H 2 O 2 and acidic pH in cells. [ABSTRACT FROM AUTHOR]

Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet–triplet energy gap (ΔE ST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR with k cat / K m as 2.18 × 104 M−1 s−1. The detection limit was determined to be 53.6 ng/mL in 80 % PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity. In addition, the probe exhibited effective ROS generation ability and significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment. Schematic Representation of the NTR-responsive fluorescence turn-on photosensitizer for lysosomes imaging and photodynamic therapy. [Display omitted] • An NTR-responsive fluorescence turn-on probe M-TPE-P for lysosomes imaging was developed. • M-TPE-P showed high selectivity and sensitivity with a low detection limit toward NTR. • M-TPE-P displayed time-dependent behaviors, excellent lysosomes targeting and ROS generation ability in 4T1 cells. • The structure relationship between the probe M-TPE-P and NTR was demonstrated by DFT and docking calculations. [ABSTRACT FROM AUTHOR]

The abnormally elevated expression level of glutathione (GSH) has been observed in various human cancer cells and tissue. Thus, effective methods for glutathione detection are of great importance in early diagnosis of cancer. However, many fluorescent probes for GSH detection suffer from the interference of the abundantly existent nucleophilic biomolecules in biological environment. In this work, we propose a sequential activation strategy to overcome this problem by designing and synthesizing a series of 1,3,5-triazinyl resorufin turn-on fluorescent probe (Probes 1–3). As two electrophilic sites are presented in probes, GSH sequentially reacts with the resorufin and the triazine moiety, resulting in significant fluorescence augmentation (up to 165.0-fold). Designed probes possess low limit of detection as low as 1.8 μM). Cellular fluorescent imaging has been successfully applied to selectively detect GSH in several living cells. [Display omitted] • Novel sequential activation strategy allows the Probe 1–3 to detect GSH with high selectivity. • Designed fluorescent probes exhibited strong fluorescence intensity as response. • Designed probes realized GSH visualization in multiple cells with high fidelity. [ABSTRACT FROM AUTHOR]

Telomerase (TE) is a promising diagnostic and prognostic biomarker for many cancers. Quantification of TE activity in living cells is of great significance in biomedical and clinical research. Conventional fluorescence-based sensors for quantification of intracellular TE may suffer from problems of fast photobleaching and auto-fluorescence of some endogenous molecules, and hence are liable to produce false negative or positive results. To address this issue, a fluorescence-SERS dual-signal nano-system for real-time imaging of intracellular TE was designed by functionalizing a bimetallic Au@Ag nanostructure with 4- p -mercaptobenzoic acid (internal standard SERS tag) and a DNA hybrid complex consisted of a telomerase primer strand and its partially complimentary strand modified with Rhodamine 6G. The bimetallic Au@Ag nanostructure serves as an excellent SERS-enhancing and fluorescence-quenching substrate. Intracellular TE will trigger the extension of the primer strand and cause the shedding of Rhodamine 6G-modified complimentary strand from the nano-system through intramolecular DNA strand displacement, resulting in the recovery of the fluorescence of Rhodamine 6G and decrease in its SERS signal. Both the fluorescence of R6G and the ratio between the SERS signals of 4- p -mercaptobenzoic acid and Rhodamine 6G can be used for in situ imaging of intracellular TE. Experimental results showed that the proposed nano-system was featured with low background, excellent cell internalization efficiency, good biocompatibility, high sensitivity, good selectivity, and robustness to false positive results. It can be used to distinguish cancer cells from normal ones, identify different types of cancer cells, as well as perform absolute quantification of intracellular TE, which endows it with great potential in clinical diagnosis, target therapy and prognosis of cancer patients. [Display omitted] • A dual-signal nanosensor was developed for imaging of telomerase in living cells. • Au@Ag nanoparticles served as fluorescence quenching and SERS enhancing substrate. • The results of the fluorescence and SERS channels can provide mutual confirmation. • The SERS channel of the nanosensor can help identify false positive results. [ABSTRACT FROM AUTHOR]

Developing simple, rapid and specific mRNA imaging strategy plays an important role in the early diagnosis of cancer and the new drugs development. Herein, we have established a novel binary system based DNA tetrahedron and fluorogenic RNA aptamers for highly specific and label-free mRNA imaging in living cells. This developed system consisted of tetrahedron probe A (TPA) and tetrahedron probe B (TPB). TK1 mRNA was chosen as the study model. After TPA and TPB enter into the live cells, the TK1 mRNA induces TPA and TPB to approach and activate the fluorescent aptamer, resulting in enhanced fluorescent signal in the presence of small molecules of DFHBI-1T. By this design, the high specificity label-free detection of nucleic acids was achieved with a detection limit of 1.34 nM. Confocal fluorescence imaging experiments had proved that this strategy could effectively distinguish the TK1 mRNA expression level between normal cell and cancer cell. The developed method is expected to provide a new tool for early diagnosis of diseases and new drug development. Schematic representation of binary system based DNA tetrahedron and fluorogenic RNA aptamers for intracellular mRNA imaging. Confocal fluorescence imaging experiments had proved that this strategy could effectively distinguish the TK1 mRNA expression level between normal cell and cancer cell. [Display omitted] • This strategy demonstrated high efficiency of DNA transfusion and biostability in living cells. • Fluorogenic RNA aptamers as indicators achieved highly sensitive label-free imaging of intracellular TK1 mRNA. • The proposed binary system strategy is facile and practical. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) is a multifunctional gaseous signaling molecule that plays a vital role in several biological processes. In the present study, a BODIPY-based fluorescent probe called 8-[4-((1,4,7,10-tetraazacyclododecane)methyl)phenyl]-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a, 4a-diaza- s -indacene (BA–Cyclen)–Cu was designed and synthesized; this probe is a Cu(Ⅱ) complex that uses Cu(Ⅱ) decomplexation to achieve the sensitive and rapid detection of aqueous H 2 S via the "turn-on" mode. We observed that BA–Cyclen–Cu exhibited good membrane permeability, low toxicity, and lysosome-targeting ability, facilitating H 2 S detection in living cells. Furthermore, we demonstrated the potential biological applications of the probe by measuring exogenous H 2 S originating from Na 2 S and GYY4137, a slow-release donor, and endogenous H 2 S generated via the catalysis of cystathionine- β -synthase in both normal (H9c2) and cancerous (U87) cells. Moreover, BA–Cyclen–Cu was successfully used to detect exogenous H 2 S by the external standard method in fetal bovine serum, the serum of a healthy person, and the serum of a patient with liver cancer. [Display omitted] • BA-Cyclen-Cu displayed high selectivity, sensitivity and fast response toward H 2 S with "turn-on" mode. • BA-Cyclen-Cu have a good performance on exogenous/endogenous H 2 S sensing in cancer cells and normal cells. • BA-Cyclen-Cu was successfully used to detect H 2 S in serum samples. [ABSTRACT FROM AUTHOR]

Hydrogen polysulfide (H 2 S n , n > 1) is an important component of reactive sulfur species (RSS), which is an important substance for maintaining the redox balance in cells. However, limited recognition moieties are available for hydrogen polysulfide probe design. In this study, we have constructed a small library containing several organic molecules to explore a new specific recognition moiety for H 2 S n fluorescent probe design. To validate the discovery, two fluorescent probes, 7 and BCC, were further developed based on coumarin and its derivative. The probes exhibited desirable specificity for H 2 S n monitoring, which can be used for detecting H 2 S n in solution and cells. The new specific recognition moiety for H 2 S n fluorescent probe design discovered in this work has certain guiding significance for development of H 2 S n probes exploring biological roles in the future. [Display omitted] • Constructed a small library to explore recognition moiety for H 2 S n probe design. • Two fluorescent probes were further developed to validate the discovery. • Probe 7 and BCC exhibited desirable application in H 2 S n monitor and cells imaging. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) as one most abundant thiol, acts as important roles in regulating cellular redox activities, and various diseases are closely related with its abnormal levels. Thus, monitoring intracellular GSH levels is essential for understanding cellular metabolism of many related diseases. In this work, we firstly reported a new fluorescence turn-on sensor, which was capable of selectively, sensitively and rapid sensing GSH over other thiols, especially cysteine and homocysteine in solutions and living cells. A meso -aryltellurium boron dipyrromethene (BODIPY) was firstly designed and synthesized, which showed silenced emission due to an efficient photoinduced electron transfer (PET) process from electron-rich Te to BODIPY, and then upon exposure to GSH, the meso -Te-C bond could be rapidly cleaved by the thiol group of GSH, thus resulting in an obvious fluorescence "turn-on" phenomenon through inhibition of the PET effect. This probe exhibited excellent selectivity and sensitivity towards GSH with a short response time of 2 min, showing a remarkable fluorescence enhancement observed at 541 nm with a large fluorescence quantum yield increase from nearly 0 to 0.73 upon excitation at 500 nm in PBS/CH 3 CN (9/1, v/v). The detection limit towards GSH was further calculated to be 1.7 nM by the linear fluorescence change at 541 nm in the GSH-concentration ranging from 0 to 4 μM. Furthermore, its sensing mechanism was validated by using mass spectrometry, confirming the rapid cleavage of the Te–C bond by GSH. Finally, cell imaging experiments demonstrated that this probe could successfully detect GSH in living cells, highlighting its potential for rapid and sensitive detection of intracellular GSH level changes. Therefore, a new meso -aryltellurium-BODIPY fluorescence turn-on sensor was firstly developed, which could selectively, sensitively and fast detect cellular GSH over other thiols based on the rapid cleavage of the meso Te–C bond. Herein, we report for the first time a novel meso -aryltellurium-BODIPY-based fluorescent probe for selective, sensitive and fast detection of GSH over other thiols with an absolutely fluorescent "turn-on" phenomenon through the substitution reaction in solutions and living cells. [Display omitted] • A meso -aryltellurium boron dipyrromethene (BODIPY) was rationally designed and synthesized. • This probe could selectively, sensitively and fast detect GSH over other thiols with an absolute fluorescence turn-on effect. • It sensing mechanism was based on the rapid cleavage of the meso Te–C bond by GSH. • Cell imaging experiments confirmed its potential for sensitive and rapid detection of intracellular GSH level changes. [ABSTRACT FROM AUTHOR]

Apple ring rot caused by Botryosphaeria dothidea can cause fruit decay during the growth and storage stages of apple fruit. Understanding the infection process and cellular defense response at the cellular micro-level holds immense importance in the field of prevention and control. Consequently, there is a pressing need to develop suitable chemical imaging analysis methods. Here we proposed a label-free, high-throughput imaging method for cellular investigation of apple fruit ring rot infected by Botryosphaeria dothidea , based on confocal Raman microspectroscopic imaging technology combined with multivariate curve resolution-alternating least squares algorithm (MCR-ALS). We conducted Raman measurements on every apple fruit and obtain an image cube. This cube was then unfolded into an augmented matrix in a column-wise manner. We proceeded with simultaneous MCR-ALS analysis, resolving the single-substance spectrum and concentration profile from the mixed signals. Lastly, the accurate and pure molecular imaging of low methoxyl pectin, high methoxyl pectin, cellulose, lignin, and phenols were realized by refolding the resolved concentration data to construct the composition image. Thereafter, we realized the study of the spatial-temporal changes distribution of the above substances in the cuticle and cell wall of green and red apples at different stages of infection. The imaging method proposed in this paper is expected to provide a chemical imaging strategy for studying pathogen infection process and fruit defense response at the cellular level. In addition, by utilizing a fiber-optic probe near-infrared reflection spectrometer in conjunction with machine learning, we developed a rapid and non-destructive classification method. This method allows for the timely identification of apples exhibiting early infection by Botryosphaeria dothidea. Notably, both principal component analysis-quadratic discriminant analysis and support vector machine achieved a classification accuracy of 100%. [Display omitted] • A label-free and high-throughput cell imaging method is proposed for apple ring rot. • The method is based on confocal Raman imaging microscopy and chemometrics. • The spatial-temporal changes of five substances in cellular level are investigated. • A rapid near-infrared based machine learning method is proposed for apple ring rot. • Identification of apples with early infection by Botryosphaeria dothidea is achieved. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are important subcellular organelles that play a huge role in cell metabolism and growth. In this study, we synthesized two LDs fluorescent probes with benzothiadiazole (BTH) as electron acceptor and triphenylamine (TPA) as electron donor, which named as TPA-BTH1 and TPA-BTH2 , respectively. Meanwhile, we introduced long alkyl chain to the probe as a shielding group and LDs targeting enhancement group. The results showed that the two probes were too sensitive to solvents' polarity because of the D-A structures possessed twisted intramolecular charge-transfer (TICT) effect. Furthermore, we prepared the two probes into nanoprobes by nanoprecipitation, which named as TPA-BTH1-20 and TPA-BTH2-20 , respectively. The nanoprobes also had excellent fluorescence emission abilities and biocompatibility, as well as high photostability and accurately target LDs ability, which could be successfully applied in cell fluorescence imaging experiments. Two liquid fluorescent probes targeted LDs were named TPA-BTH1 and TPA-BTH2, which showed a response to polarity of solvent. Then we prepared them into FONs by wrapping with PLGA through nanoprecipitation, and the FONs all owned excellent fluorescence emission efficiency, photostability, good dispersion in water, and better stability in cells, including photostability and resistance to photobleaching. [Display omitted] • The fluorescent probes and their nanoprobes all had high luminescence efficiency • The nanoprobes possessed excellent continuous and stable luminescence capability • The nanoprobe had precisely targeting ability to LDs [ABSTRACT FROM AUTHOR]

Hydrazine (N 2 H 4) plays an important role in industrial production, but it is highly toxic, leaking or exposing it will pollute the environment and cause serious harm to human beings. Therefore, it is necessary to use a simple and effective method to detect N 2 H 4 in environmental systems and organisms. Herein, a novel water-soluble fluorescent probe based on coumarin fluorophore, 2-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)isoindoline-1,3-dione (C-Z1), is reported. The fluorescence intensity of the probe at 530 nm was enhanced gradually with the addition of N 2 H 4 , and the maximum enhancement was about 28 times. The probe has good selectivity and sensitivity, the detection limit of hydrazine hydrate is 1.48 × 10−7 M, and the response mechanism of the probe is proved by theoretical calculation and experiment. C-Z1 has been shown to detect N 2 H 4 in a variety of environmental samples, including water, soil, air, cells, zebrafish and plants. In addition, C-Z1 can be made into test strips for easy portability and used for rapid quantitative detection of N 2 H 4 in the field by its distinct change in fluorescence color. Thus, C-Z1 has great potential for the analysis and detection of environmental contaminants. In this paper, the deprotection of phthalimide is used as a strategy for the detection of hydrazine. We designed and synthesized a water-soluble probe C-Z1 for the detection of N 2 H 4. its absorption and emission spectra vary regularly with the concentration of the N 2 H 4 solution. C-Z1 can detect N 2 H 4 in environmental water samples, soil, and air. Portable paper test strips based on C-Z1 can be easily prepared and are well used for in situ detection of N 2 H 4. Most importantly, the successful application of the probe in cell imaging, zebrafish imaging, and Arabidopsis imaging demonstrates the potential application of the probe in biological and environmental aspects. [Display omitted] • C-Z1 is a novel probe for the detection of N 2 H 4 , which has not been reported in other literature. • The probe is a water-soluble fluorescent probe and has a maximum fluorescence intensity of 28-fold. • The probe possesses low toxicity and can be used for fluorescence imaging of cells, zebrafish and arabidopsis. • Accurate determination of hydrazine is realized in real environmental samples. • The probes are simple to prepare and can be made into test strips for physical environmental testing. [ABSTRACT FROM AUTHOR]

Improving the accuracy, sensitivity and speed of intracellular miRNA imaging is essential for early diagnosis of cancer. To achieve this goal, we herein present a strategy for imaging two distinct miRNAs by DNA tetrahedron-based catalytic hairpin assembly (DCHA). Two nanoprobes, DTH-13 and DTH-24, were prepared by one-pot synthesis. The resultant structures were DNA tetrahedrons functionalized with two sets of CHA hairpins, which respectively responded to miR-21 and miR-155. Using these structured DNA nanoparticles as the carriers, the probes could easily enter living cells. The presence of miR-21 or miR-155 could trigger CHA between DTH-13 and DTH-24, leading to independent fluorescence signals of FAM and Cy3. In this system, the sensitivity and kinetics were significantly enhanced owing to the strategy of DCHA. The sensing performance of our method was thoroughly investigated in buffers, fetal bovine serum (FBS) solutions, living cells, and clinical tissue samples. The results validated the potential of DTH nanoprobes as a diagnostic tool for early stages of cancer. [Display omitted] • DNA tetrahedron-based catalytic hairpin assembly was firstly employed for the imaging of two distinct miRNAs. • The system generates independent fluorescence signals in the presence of miR-21 or miR-155. • The system was applied for miRNA detection in the buffers, serum solutions, living cells, and clinical tissue samples. • The detection limit at the picomolar level was achieved in the buffers and serum solutions. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is a biomolecule that plays a critical part in the functioning of our brains by promoting motivation, maintaining focus, and altering mood. Excessive or low-level concentrations of DA in the human brain led to a dangerous neurological disorder. It is significantly important to trace the precise amount of DA to prevent such risky brain disease. Recently, heteroatoms-doped carbon dots (H-CDs) have attracted great attention for their capacity to detect biomolecules, metal ions, organic solvents, chemical dyes, etc. In this review, we have provided a comprehensive summary of the emerging trends in the heteroatom functional dopamine-doped carbon dots (DA-CDs), which are based on DA used as starting substances or functionalizing agents. Our analysis encompasses a detailed exploration of the synthetic methods, physical and chemical properties of carbon dots derived from dopamine, as well as their diverse range of applications. Additionally, we have also discussed the application of H-CDs in the dopmine detection by using various fluorescent, colorimetric, and electrochemical techniques. [Display omitted] • A comprehensive summary of heteroatoms-doped carbon dots based on dopamine as hybrid agents or detected substances. • The introduction of physicochemical properties and application for dopamine-synthesized or functionalized CDs.To discuss the application of heteroatoms-doped carbon dots (H-CDs) in dopamine detection. • To discuss the application of heteroatoms-doped carbon dots (H-CDs) in dopamine detection. [ABSTRACT FROM AUTHOR]

Fluorogenic substrates are used to visualize the activity of cancer-associated enzymes and to interpret biological events. Certain types of glutathione S-transferase (GST), such as Pi class GST (referred to as GSTP1), are more highly expressed in a wide variety of human cancer tissues compared to their corresponding normal tissues. Pi class GST is thus a cancer cell molecular marker and potential target for overcoming resistance to chemotherapy. Here, we report that 4-bromo-1,8-naphthalimide (BrNaph) is a practical fluorogenic GST substrate. We have found that HE-BrNaph , an N -hydroxyethyl derivative, shows remarkable fluorescence enhancement upon GST-catalyzed S N Ar replacement of the bromo group with a glutathionyl group. This substitution was highly selective and occurred only in the presence of GSH/GSTs; no non-enzymatic reaction was observed. We demonstrated that HE-BrNaph allows visualization of GST activity in living cells and enables to distinguish cancer cells from normal cells. Further, various N -substitutions in BrNaph retain susceptibility to enzymatic activity and isozyme selectivity, suggesting the applicability of BrNaph derivatives. Thus, BrNaph and its derivatives are GST substrates useful for fluorescence imaging and the intracellular detection of GSTP1 activity in living cells. Image 1 • HE-BrNaph shows a large fluorescence enhancement upon catalysis by GST. • HE-BrNaph was used for live cell imaging of GSTP1 activity. • Various N -substitutions in BrNaph were tolerated by the enzymatic reaction and maintained isozyme selectivity. [ABSTRACT FROM AUTHOR]

In this paper, a new strategy was presented for fluorescence labeling and imaging Al3+ in live cells with excess aluminum ions using thiolated fluorescence gold nanoclusters (Au NCs). The glutathione (GSH)-capped Au NCs were prepared via a green, facile one-pot method in aqueous solution and displayed excellent stability, ultrasmall size, monodispersity, and larger Stokes shift, which exhibits a relatively weak fluorescence at 650 nm Al3+-induced fluorescence enhancement of the GSH-Au NCs can be observed due to Al3+-triggered aggregation-induced emission (AIE) effect, which allows the role of GSH-Au NCs as a fluorescence light-up probe for detection of Al3+. Moreover, it was demonstrated that the fluorescence probe for Al3+ showed a wide detection range from 100 to 600 μM and good selectivity against other metal ions and common biomolecule. Furthermore, due to the advantages of excellent biocompatibility, low toxicity, red emission and high specificity, the proposed GSH-Au NCs fluorescence probes are suitable for the imaging of high concentrations of aluminum ions in cells, which can be applied to the diagnosis of cellular aluminum poisoning. Schematic illustration of the synthesis process of GSH-Au NCs and the fluorescence enhancement of GSH-Au NCs after adding Al ion due to the Al3+ triggered aggregation of the GSH-Au NCs. Image 1 • First report of the Al3+ rapid fluorescence detection in live cells with excess aluminum ions using thiolated Au NCs. • Al3+ as linkers can induce photoluminescence boost of thiolated Au NCs nearly 40-fold through AIE. • The biosensor is suitable for imaging of excess aluminum ions in cells due to their hypotoxicity, red emission of 650 nm. [ABSTRACT FROM AUTHOR]

Cys is one of the important biothiols and its abnormal concentration may pose a threat to human health. Therefore, the monitoring of Cys in organisms is of great significance. GSH and Hcy, as the other two biothiols, have similar chemical structures and active sites to Cys. Consequently, developing fluorescent probes to independently detect Cys has become a challenging problem. Keeping this in mind, α-β unsaturated ketone as a recognition group was integrated into the coumarin group skeleton to synthesize a fluorescent probe SC. After the nucleophilic addition reaction of Cys with SC , the conjugated system of SC was blocked and the fluorescent enhanced obviously. SC was able to detect Cys specifically under the same excitation with a low detection limit (11.1 nM). SC showed a rapid respond to Cys (120 s) and good fluorescent stability over a wide pH range. In addition, it achieved extracorporeal circulation in the presence of H 2 O 2 or NEM. In the end, SC could be applied to detecting endogenous and exogenous Cys under biological condition due to its slight cytotoxicity and good biocompatibility. This provided a powerful tool for studying the physiological function of Cys exclusively. Image 1 • The probe SC possessed a high specificity of Cys over Hcy and GSH under the same excitation and test system. • SC had satisfactory reversibility in the presence of NEM or H 2 O 2. • SC displayed a fast response to Cys (120 s). • Cytotoxicity test indicated that probe SC had very low cytotoxicity even at the concentration of 100 µM. • The probe SC could be used to monitor endogenous and exogenous Cys in living cells. [ABSTRACT FROM AUTHOR]

Hepatocarcinoma is the second leading cause of cancer-related death worldwide accompanied by the aberrant expression of many genes. Among of them, p53 and p21 genes played a vital role in the development of liver cancer. Thus, monitoring mRNA levels of the two markers is urgently needed for early diagnosis and understanding the molecular mechanism of hepatocarcinoma development. Herein, a functional nanosystem for in situ and real-time monitoring levels of p53 and p21 mRNA was constructed using reduced graphene oxide nanosheet assisted fluorescence probes. Comparing with traditional methods, the new method indicated high sensitivity and outstanding selectivity towards p53 and p21 mRNA assay in vitro. Moreover, the functional nanosystem was successfully used for monitoring dynamic change of mRNAs in HepG2 cells caused by cisplatin treatment, the reliability of which was confirmed by RT-PCR. In summary, this strategy provides a promising tool to reveal p53 and p21 mRNA regulatory process in cancer cells, which is practicable for drug screening and therapy evaluation on clinic. Image 1 • The synthetic rGONS displays outstanding fluorescence quenching efficiency, excellent biocompatibility, high cell uptake efficiency and strong anti-nuclease capability in living cells. • The nanosystem displays the ability of high sensitivity, strong specificity, and rapid detection of target mRNA in vitro. • The nanosystem enables dynamic monitoring of double mRNA levels in living cancer cell. [ABSTRACT FROM AUTHOR]

In this work, we designed a kind of novel fluorescent probes based on naphthalene-benzoindole conjugate derived for sensitively monitoring the pH fluctuation in environment and biological systems. In the spectral method, these two probes both show significant red shift, color change and fluorescence quenching due to the effect of intramolecular charge transfer (ICT) mechanism. Moreover, we found that the probe bearing with carboxyl group displayed a more hydrophilicity than the one bearing with hydrogen atom instead, and the former exhibits a faster response and higher fluorescence intensity. Besides, the probe bearing with carboxyl group shows lower cytotoxicity, evidences by the vitro study. It indicates that this probe has great potential in application in living cell imaging as well as pH-fluctuation monitoring. Image 1 • The pH-responsive of probes were realized via ICT mechanism. • L2 had better water solubility than L1 due to the existence of carboxyl. • The probes could detect quantitatively of pH value by a fluorescence method. • The probes could monitor the physiological pH fluctuations. [ABSTRACT FROM AUTHOR]

A fluorescence-enhanced and lysosome-targeted Al3+ probe (1) based on a pyrazole-containing hydrazone was developed in this work. The fluorescent probe 1 displays an OFF–ON fluorescence response to Al3+ in the lysosome pH environment. In addition, the resultant 1 –Al3+ complex could act as an ON–OFF fluorescence sensor for F−. Fluorescence imaging shows that 1 is suitable for visualization of Al3+ in lysosomes of HeLa cells. Image 1 • A quite simple hydrazone-based fluorescent probe for Al3+ has been developed. • The probe displayed an OFF-ON response toward Al3+ in aqueous solution. • The resultant Al3+ complex of the probe could act as an on-off fluorescent sensor for F−. • The probe has been used for imaging of Al3+ in lysosomes of HeLa cells. [ABSTRACT FROM AUTHOR]

Two kinds of carbon dots (CDs) with different solubility, aqueous soluble CDs (ACDs) and organic soluble CDs (OCDs), were produced at the same time by one step hydrothermal synthesis method using sorbic acid and proline as carbon precursor and nitrogen dopant, respectively. The synthesized CDs were characterized by means of UV, fluorescence, TEM, elemental analysis, IR and XPS et al. Based on the effective and proportional fluorescence quenching by Cr(VI), ACDs were successfully used as a high sensitive and selective probe for Cr(VI) detection. Internal filtration effect (IFE) played an important role in the quenching process. Under the optimal conditions, linear response for Cr(Ⅵ) was observed in the range of 0.5–100 μmol/L, and the calculated detection limit was 34 nmol/L. The method has been satisfactorily applied to detect Cr(VI) ions in real water samples of our campus. Then, the ACDs were further applied for cell imaging in B16F10 cells. Furthermore, OCDs were well dispersed into PMMA to fabricate OCDs/PMMA composites as fluorescent films. ACDs and OCDs were produced at the same time and their multi-functional applications were explored like Cr(Ⅵ) detection, bioimaging, and OCDs/PMMA films. Image 1 • Two kinds of CDs were simply synthesized by one-step hydrothermal method directly. • The fluorescence of ACDs can be selectively quenched by Cr(VI) and applied to detect Cr(VI) in real water samples. • The ACDs are successfully applied for cell imaging in B16F10 Cells. • The OCDs/PMMA composites have been fabricated as fluorescent films. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) was considered as an effective treatment. Whereas only PDT is not enough to achieve effective therapy on account of irradiation intensity decreases as depth increases as well as tumor hypoxia. Combination with gene therapy and photodynamic therapy have emerged as an effective strategy to improve therapeutic effectiveness. In the present study, a GSH responsive MnO 2 was employed to delivery TB and DNAzyme for cancer imaging and PDT-gene combination treatment. TB, a photosensiters with aggregation-induced emission characteristic, was employed for photodynamic therapy, while DNAzyme, acting as catalysts for the degradation of EGR-1 mRNA, was exploited for gene silencing. All of the results of tumor treatment in vitro have implied that MnO 2 -DNAzyme-TB nanocomposite (MDT) can internalize into cells. Subsequently, MDT could decrease the expression of EGR-1 by gene silencing that enabling inhibition of cell growth. In addition, the singlet oxygen which was generated by the aggregated TB were able to further suppress cell growth. Combination therapy of photodynamic as well as gene therapy greatly enhanced antitumor efficiencies. Furthermore, in vivo tumor treatment experiments demonstrated that MDT under illumination can effectively inhibit the tumor growth of MCF-7 tumor-bearing mice by photodynamic and gene silencing combination therapy. Image 1 • A GSH reponsive delivery system was successfully farbricated. • The MnO 2 -DNAzyme-TB nanocomposite provides the capability of cell imaging. • The delivery system exhibits effective inhibition toward tumor via combination therapy both photodynamic therapy and gene silencing. [ABSTRACT FROM AUTHOR]

In this study, we developed a new fluorescent probe (CMM) based on coumarin dye and malononitrile, for highly sensitive and selective detection of hypochlorite ion (ClO−). CMM showed a 45-fold fluorescence enhancement at 459 nm in the presence of ClO− and displayed an excellent selectivity over other competing species. The probe featured a fast response time (<15 s), which could be in favor of the real-time detection towards ClO−. Meanwhile, probe CMM could effectively monitor ClO− in physiological pH condition and the detection limit was estimated to be as low as 5.7 nM. Furthermore, its preeminent recognition properties made the successful application for monitoring ClO− in environmental water samples and labeling ClO− in living biological cells. Image 1 • A coumarin-based "turn-on" fluorescent probe for hypochlorite was developed. • The probe detect ClO− with high selectivity and low detection limit. • The probe is able to detect ClO− within 15 s. • The probe is successfully applied to detect ClO− in real water samples and living cells. [ABSTRACT FROM AUTHOR]

It is necessary to develop simple and highly sensitive methods for the detection of hypochlorous acid (HOCl)/hypochlorite (ClO−) to ravel its relationship with disease. In this paper, a novel bio-compatible fluorescent (Z)-8-(hydrazonomethyl)-7-hydroxy-4-methyl-2H-chromen-2-one (probe 1b) based on coumarin was synthesized and used for detecting ClO− in PBS buffer (pH = 7.2, 10 mM, 60% C 2 H 5 OH). Probe 1b showed a remarkable fluorescence change from yellow to blue with the limit of detection as low as 2.4 × 10−9 M−1 when ClO− was added. The coexisted anions, metal ions and reactive oxygen species (•OH, 1O 2 , H 2 O 2 , KO 2) showed any competitiveness towards ClO−. In response to ClO−, the fluorescence emission intensity of probe 1b was obviously enhanced within 20 s. The mechanism was confirmed by the ESI - MS and density functional theory calculations (DFT) to reveal that the coumarin lactone bonds C − O was cleavaged by oxidation of ClO − . What's more, probe 1b could be used in practical water samples and showed well recovery. Additionally, the cell imaging experiment was demonstrated that probe 1b could be effectively exploited to imaging exogenous ClO− in vitro. A new probe 1b was designed and synthesized for highly specific and sensitive detection of ClO− with fast response time in living cells. Image 1 • A novel fluorescent probe 1b based on coumarin was designed and synthesized. • The probe 1b could be used for highly specific and sensitive detection of ClO− with fast response time. • The probe 1b could quantitatively detect ClO− in real environmental water samples. • The probe 1b was successfully applied to monitor ClO− in living cells. • ESI-MS and DFT were further verified that the oxidation reaction between the C O of coumarin lactone and ClO−. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world, which can lead to considerably high mortality rate. It was reported that the prognosis is extremely poor and survival is often measured in months once CRC metastases become clinically evident. Therefore, the development of effective approach for metastatic CRC cells detection and imaging may potentially be significant and helpful for CRC prognosis and treatment. Therefore, we proposed a sensitive and specific approach for high-metastatic CRC LoVo cells detection and imaging by using terminal deoxynucleotidyl transferase (TdT)-initiated molecule beacons (MBs) arrayed fluorescent aptamer probes (denoted as TMAP). In this approach, the aptamer W3 targeting high-metastatic CRC LoVo cells was elongated to form W3-poly A at the 3′-hydroxyl terminus with repeated A bases in the presence of TdT and dATP. The MBs designed with poly T sequence in the loop were then hybridized with the poly A in the aptamer W3. The TMAP was easily constructed without the need of aptamer modification. It was demonstrated that this approach could specifically detect and image the high-metastatic CRC LoVo cells from the mixture of high-metastatic CRC LoVo cells and non-metastatic HCT-8 cells. Compared with 6-carboxyfluorescein (6-FAM) labeled aptamer W3, the TMAP was demonstrated to have a much stronger fluorescence signal on the target cells, realizing a 4-fold increase in signal-to-background ratio (SBR). Determination by flow cytometry allowed for detection of as low as 23 CRC LoVo cells in 200 μL cell culture medium. The high sensitivity and the capability for using in complicate biological samples imply that this approach holds considerable potential for metastatic CRC detection and therapy. Image 1 • TMAP was developed for specific detection and imaging of metastatic CRC cells. • TMAP could identify target LoVo cells with excellent binding affinity and specificity. • TMAP could specifically distinguish between the metastatic LoVo cells and non-metastatic HCT-8 cells in mixed cells samples. [ABSTRACT FROM AUTHOR]

Hypochloric acid (HOCl) plays vital roles in cell signaling and homeostasis which involved in many related diseases. Therefore, the accurate detected level of OCl− for discussing the complex contributions of OCl− to human health is of great significance. In this study, a novel mitochondrion-targeting fluorescent probe DMI bearing a carbon-carbon double bond as an OCl−-responsive site has been developed. Probe DMI exhibited specific fluorescence response toward OCl− with fast response (within 4 s) and high sensitivity (detection limit is 0.05 μM), where the obvious color changes could be observed by the naked eye. More importantly, DMI could be applied in the bioimaging of OCl− in living A549 cells successfully benefited from its good sensing properties and low toxicity. Fluorescence co-localization test was further carried out and confirmed mitochondria-targetable ability of DMI which can be used for investigating physiological function of HOCl at organelle levels. Image 1 • Probe DMI is a mitochondria-targeting visual fluorescence probe. • DMI could highly sensitive and selective detected of hypochlorite. • The mechanism of DMI has been proved to be via oxidation fracture of C C. • DMI can be used to imaging of OCl− in living A549 cells. [ABSTRACT FROM AUTHOR]

Two different colors of water-soluble core-shell quantum dots CdTe/CdS (green and orange red) have been synthesized and characterized in this paper. The formation of core-shell quantum dots not only improves the fluorescence quantum yield, but also reduces the biological toxicity of quantum dots, and improves the fluorescence lifetime. Two novel fluorescent bioprobes, CdTe/CdS (λ em = 545 nm)-5-Fu and Bio-CdTe/CdS (λ em = 600 nm)-TAM, have been synthesized via the interaction of these two core-shell quantum dots with anticancer drugs (5-Fu) and P-gp inhibitors (TAM), respectively. These two fluorescent probes have been simultaneously used in fluorescence imaging of human breast cancer cells MDA-MB-231/MDR. It can be observed that under the action of P-gp inhibitors distributed on the cell membrane, anticancer drugs can be retained in cancer cells. According to the color of quantum dots on the probe, the visualization results of the action of anticancer drugs and P-gp inhibitors can be obtained. This study shows that to prepare functional bioprobes using core-shell quantum dots CdTe/CdS has great potential in the field of biomedical research such as anticancer drugs. Image 1 • CdTe/CdS core-shell QDs has higher fluorescence quantum yield and lower biological toxicity. • Simultaneous imaging of two bioprobes (CdTe/CdS-5-Fu, Bio-CdTe/CdS-TAM) in cancer cells. • Surface functionalization of quantum dots by anticancer drugs 5-Fu and P-gp inhibitors TAM. • Two colors bioprobes visualize the Interaction between Anticancer Drugs and P-gp Inhibitors. [ABSTRACT FROM AUTHOR]

A novel ratiometric fluorescence probe for hypochlorous acid was constructed by coumarin and pyridinium fluorophore based on the Forster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) platform. In this ICT/FRET system, the energy transfer efficiency is high to 94.3%. Moreover, the probe could respond to hypochlorous acid with high selectivity and sensitivity, and exhibited a large Stokes shift. It was interesting to find that the probe could recognize hypochlorous acid via a new mechanism, in which the α-position of carbonyl group was oxidized to form a diketone derivative. More importantly, the probe was successfully applied to the ratiometric imaging of both exogenous and endogenous hypochlorous acid in living RAW 264.7 cells, with low toxicity and high photo-stability. Image 1 • A ratiometric fluorescent probe ZPAC for rapidly monitoring hypochlorous acid. • A new mechanism, α position of carbonyl group was oxidized to form a diketone derivative. • FRET-based ZPAC displayed larger gap between two emission spectrum. • ZPAC was applied to image exogenous and endogenous hypochlorous acid in living RAW264.7 cells. [ABSTRACT FROM AUTHOR]

An effective dithiourea-appended 1,8-naphthalimide fluorescent probe was designed and synthesized. This probe could recognize Hg2+ and Ag+ sensitively and selectively in neutral and alkaline conditions. Moreover, the probe detected Hg2+ alone at pH between 2 and 6. The sensing ability of the probe was explored by UV–vis, fluorescence, FTIR and 1H NMR spectroscopy. The probe was quenched by Hg2+ and Ag+ with 1:1 binding ratios in MeCN/H 2 O (4/1, v/v) mixed solution with binding constants of 3.76 × 104 L mol−1 and 2.47 × 104 L mol−1, respectively. The linear concentration ranges for Hg2+ and Ag+ were 0–17 μmol L−1 and 0–24 μmol L−1 with detection limits of 0.83 μmol L−1 and 1.20 μmol L−1, respectively, which allowed for the quantitative determination of Hg2+ and Ag+. The new probe, 3a, was successfully applied to the fluorescence imaging of Hg2+ and Ag+ in HepG2 cells, demonstrating its potential application in biological science. Moreover, 3a was used to measure Hg2+ and Ag+ in tap water, drinking water and ultrapure water samples. The recoveries of Hg2+ and Ag+ in water samples were 96–99% and 98–103%, respectively. Therefore, the proposed method showed promising perspectives for its application, aimed at detecting Hg2+ and Ag+ in fluorescence imaging and real water samples. fx1 • A new dithiourea-appended 1,8-naphthalimide probe for detecting Hg2+ and Ag+ has been developed. • The probe could be used to detect Hg2+ at pH 2 ~ 6 individually. • The probe was evaluated by the determination of spiked Hg2+ and Ag+ in real water samples. • The detection of Hg2+ and Ag+ in liver cancer cells using this probe had been achieved. [ABSTRACT FROM AUTHOR]

Tumor cell exosomes play a very important role in the process of tumor cell proliferation and metastasis. However, due to the nanoscale size and high heterogeneity of exosomes, in-depth understanding of their appearance and biological characteristics is still lacking. Expansion microscopy (ExM) is a method that embeds biological samples in a swellable gel to physically magnify the samples to improve the imaging resolution. Before the emergence of ExM, scientists had invented several super-resolution imaging techniques that could break the diffraction limit. Among them, single molecule localization microscopy (SMLM) usually has the best spatial resolution (20–50 nm). However, considering the small size of exosomes (30–150 nm), the resolution of SMLM is still not high enough for detailed imaging of exosomes. Hence, we propose a tumor cell exosomes imaging method that combines ExM and SMLM (i.e. Expansion SMLM, denoted as ExSMLM), which can realize the expansion and super-resolution imaging of tumor cell exosomes. In this technique, immunofluorescence was first performed to fluorescently label the protein markers on the exosomes, then the exosomes were polymerized into a swellable polyelectrolyte gel. The electrolytic nature of the gel made the fluorescently labeled exosomes undergo isotropic linear physical expansion. The expansion factor obtained in the experiment was about 4.6. Finally, SMLM imaging of the expanded exosomes was performed. Owing to the improved resolution of ExSMLM, nanoscale substructures of closely packed proteins were observed on single exosomes, which has never been achieved before. With such a high resolution, ExSMLM would have a great potential in detailed investigation of exosomes and exosome-related biological processes. [Display omitted] • An imaging method (denoted as ExSMLM) which can realize the expansion and super-resolution imaging of exosomes is proposed. • The expansion factor obtained in the experiment was about 4.6. • Nanoscale substructures of closely packed proteins were observed on single exosomes, which has never been achieved before. [ABSTRACT FROM AUTHOR]

Sensing Hg2+ is significant to protecting human health and environmental ecosystems, for its toxicity and genotoxicity. Here, highly stable fluorescent folic acid (FA)-protected Au nanoclusters (FA-AuNCs) were synthesized by optimizing the reactive parameters with high quantum yield of 34.7%. Main components of Au 4 L were confirmed by MALDI-TOF, and the electron-rich residues of FA shell enabled FA-AuNCs excellent photostability. FA-AuNCs exhibited sensitive response behavior to Hg2+ with a minimum detectability of 1.3 nM, and presented extreme effect to the detection of Hg2+ in real water. Notably, the cellular imaging and in-situ detection of Hg2+ in cells can be achieved visually. The high selectivity was attributed to the chemical bond formed between Au+ (4f145d10) and Hg2+ (4f145d10). And the internal filter effect and static quenching effect were proved triggering the quenching of FA-AuNCs. The ultra-stable FA-AuNCs provide a potential promising opportunity for the in-situ tracing Hg2+ from environmental and biological samples. [Display omitted] • Modulating synthesis of FA-AuNCs with superior photostability. • FA-AuNCs exhibit sensitive and selective detection for Hg2+ with limit of 1.3 nM. • The cellular imaging and detection for Hg2+ in cells can be achieved. • Satisfied recovery were obtained by detection of Hg2+ in real water samples. [ABSTRACT FROM AUTHOR]

Theranostic probe is becoming a powerful tool for diagnosis and treatment of cancer. Although some theranostic probes have been successfully developed, there is still a great room for improvement in sensitive diagnosis and efficient treatment. Herein, we developed a novel GSH-activable theranostic probe NC-G , which uses 1,8-naphthalimide-4-sulfonamide as a fluorescence imaging group and crizotinib as a highly toxic kinase inhibitor to tumor cells. The probe not only has high sensitivity (DL = 74 nM) and specificity, but also can detect GSH sensitively in cells and zebrafish. In addition, probe NC-G can not only show more obvious fluorescence in tumor cells to achieve sensitive diagnosis of tumor cells, but also release the inhibitor crizotinib to achieve high toxicity to tumor cells. It is worth noting that the consumption of GSH can cause oxidative stress response of cells and the release of SO 2 can induce cell apoptosis during the recognition process of the probe and GSH. Thus, the synergistic effect of crizotinib, GSH depletion, and SO 2 release provides a highly effective therapeutic feature for tumor cells. Therefore, probe NC-G can serve as an excellent theranostic probe for sensitive imaging and highly effective treatment of tumor cells. [Display omitted] • Probe can use the highly expressed GSH in tumor cells to screen tumor cells. • Probe can release the highly toxic crizotinib, a kinase inhibitor targeting c-met. • Synergistic toxicity is achieved by crizotinib release, GSH depletion and SO 2 release. • Probe can realize sensitive detection of GSH in tumor cells and zebrafish. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) is present in almost every cell in the body and plays various integral roles in many biological processes. The Golgi apparatus is a eukaryotic organelle for the biosynthesis, intracellular distribution, and secretion of various macromolecules; however, the mechanism of GSH in the Golgi apparatus has not been fully elucidated. Here, specific and sensitive sulfur-nitrogen co-doped carbon dots (SNCDs) with orange-red fluorescence was synthesized for the detection of GSH in the Golgi apparatus. The SNCDs have a Stokes shift of 147 nm and excellent fluorescence stability, and they exhibited excellent selectivity and high sensitivity to GSH. The linear response of the SNCDs to GSH was in the range of 10–460 μM (LOD = 0.25 μΜ). More importantly, we used SNCDs with excellent optical properties and low cytotoxicity as probes, and successfully realized golgi imaging in HeLa cells and GSH detection at the same time. [Display omitted] • SNCD shows excitation independent emission at 562 nm and has a large Stock shift. • SNCD has the outstanding selection, which can distinguish GSH from Cys and Hcy. • SNCDs could specifically target Golgi apparatus. • SNCDs can detect GSH while imaging Golgi apparatus. [ABSTRACT FROM AUTHOR]

The objective of the study is, for the first time, to construct a new near infrared (NIR) fluorophore, spectrophotometric, colorimetric, ratiometric, and turn-on probe (CSME) based on chromenylium cyanine platform decorated with methionine biomolecule to provide an efficient solution for critical shortcoming to be encountered for analysis of hazardous Hg2+ in environment and living cell. The CSME structure and its interaction with Hg2+ ion were evaluated by NMR, FTIR, MS, UV–Vis and fluorescence methods as well as Density Functional Theory (DFT) calculations. The none fluorescence CSME having spirolactam ring only interacted with Hg2+ in aqueous solution including competing ions. This interaction caused the fluorescence CSME with opened spirolactam form which exhibited spectral and colorimetric changes in the NIR region. The probe based on UV–Vis and fluorescence techniques respond in 90 s, has wide linear ranges (for UV–Vis: 6.29 × 10−8 – 1.86 × 10−4 M; for fluorescence: 9.49 × 10−9 – 1.13 × 10−5 M), and has a lower Limit of Detection (LOD) value (for fluorescence: 4.93 × 10−9 M, 0.99 ng/mL) than the value predicted by the US Environmental Protection Agency (EPA) organization. Hg2+ analysis was performed in drinking and tap water with low Relative Standard Deviation (RSD) values and high recovery. Smartphone and living cell applications were successfully performed for colorimetric sensing Hg2+ in real samples and 3T3 cells, respectively. [Display omitted] • A new Hg2+-probe based on a modified chromenylium cyanine platform was constructed. • It shows spectrophotometric, colorimetric, ratiometric and turn-on response in the NIR region. • Trace Hg2+ recognition was realized by the probe in the aqueous solution and living cells. • It offers a way out to common shortcomings encountered in Hg2+ sensing. • Smartphone and living cell applications for monitoring Hg2+ are simple and reliable. [ABSTRACT FROM AUTHOR]

Abstract In pure water system, the specific and rapid detection of cysteine (Cys) is very important and challenging. Herein, a new optical probe was developed for the purpose based on the complex of cupric ion (Cu2+) with a water-soluble conjugated polymer, poly[3-(3- N,N -diacetateaminopropoxy)-4-methyl thiophene disodium salts] (PTCO 2). The fluorescence of PTCO 2 in 100% aqueous solution can almost completely extinguished by Cu2+ ions due to its intrinsic paramagnetic properties. Among various amino acids, only Cys causes immediately the efficient recovery of the Cu2+-quenched fluorescence of PTCO 2 with ~31-folds fluorescence enhancement because of the stronger affinity of Cys to Cu2+ leading to the formation of Cu2+-Cys complex through Cu-S bond and separation of Cu2+ from weak-fluorescent PTCO 2 - Cu(II) ensemble and thereby restoring the free PTCO 2 fluorescence. In tris-HCl buffer solution (2 mM, pH 7.4), the intensity of the restored fluorescence is linear with the concentration of Cys, ranging from 0 to 120 μM and the estimated detection limit of Cys is 3.3 × 10−7 M with the correlation coefficient R = 0.9981. In addition, the PTCO 2 -Cu(II) ensemble probe exhibits low cytotoxicity and good membrane penetration, and its application in living cell imaging of Cys has also been explored. Graphical abstract Specific and fast detection of cysteine (Cys) in pure water was achieved based on a new fluorescent probe PTCO 2 -Cu(II) through replacement strategy. The probe also shows good pH-stability, membrane penetration and biocompatibility, and can be applied to cell imaging of Cys. fx1 Highlights • A specific probe for fast detection of Cys in 100% water was developed. • The probe showed good biocompatibility, and was suitable for cell imaging of Cys. • The sensing mechanism was demonstrated by DFT simulations and XPS study. [ABSTRACT FROM AUTHOR]

Abstract A new simple pyrene based schiff base chemosensor 1 (nicotinic acid pyren-1-ylmethylene-hydrazide) has been constructed and is prepared from 1-pyrenecarboxaldehyde and nicotinic hydrazide. Notably, the chemosensor 1 exhibited remarkable colour changes while in the presence of trivalent metal ions like Bi3+ & Al3+ ion in DMSO-H 2 O, (1:1 v/v, HEPES = 50 mM, pH = 7.4). The UV–Vis spectral investigation of chemosensor 1 showed that the maximum absorption peak appeared at 378 nm. In emission studies, chemosensor 1 develops weak fluorescence, while upon the addition of Bi3+ and Al3+ ions, it exhibits an enhancement of fluorescence intensity. Nevertheless, rest of metal ions have no changes in the emission spectra. The association constant of chemosensor 1 for binding to Bi3+ & Al3+ system had a value of 1.27 × 104 M−1 and 1.53 × 104 M−1. The detection limits were 0.12 µM for Bi3+ and 0.17 µM for Al3+ respectively. The overall results reveal that chemosensor 1 can act as a dual-channel, highly selective, and sensitive probe for Bi3+ and Al3+ ions. Moreover, the fluorescence imaging of chemosensor 1 was applied in RAW 264.7 cell line and cytotoxicity assay prove that this chemosensor 1 is non-toxic as well as highly biocompatible. Graphical abstract A new pyrene based schiff base derivative (chemosensor 1) was designed and synthesized for the detection of dual metal ions Bi3+ and Al3+ ions with live cell imaging. fx1 Highlights • A new simple pyrene based Schiff's base chemosensor 1 was designed and synthesized. • The chemosensor 1 has enhanced fluorescence intensity and dual response to Bi3+ and Al3+ ions. • The binding interaction was confirmed by Job's plot. • Chemosensor 1 utilized for fluorescence imaging of Bi3+ and Al3+ in RAW 264.7 cell line. [ABSTRACT FROM AUTHOR]

Abstract Nitric oxide (NO) plays vital roles in many physiological process and is closely related to many diseases. So far, a number of fluorescent probes have been constructed for the detection of NO successfully. However, the probes still suffer from long-time reaction and limited selectivity. Herein, a fluorescent probe named dRB-OPD is synthesized and used to recognize NO. The probe contains a deoxy-rhodamine B as fluorophore and o-phenylenediamino as reaction site. dRB-OPD shows fast response to NO within 40 s with 170-fold fluorescence enhancement. Moreover, the probe shows high selectivity towards NO over dehydroascorbic acid (DHA), ascorbic acid (AA), and methylglyoxal (MGO). Particularly, the probe can avoid the serious interference from cysteine (Cys) found in the rhodamine lactam-based fluorescent NO probes (RB-OPD). In addition, the probe is applied for the detection of exogenous and endogenous NO in the HepG2 and RAW 264.7 cells with satisfactory results. Graphical abstract fx1 Highlights • A fluorescent probe named dRB-OPD is synthesized and used to recognize NO. • The probe has fast response to NO within seconds (< 40 s). • The probe shows high selectivity towards NO over DHA, AA, and MGO. • dRB-OPD can avoid the serious interference from cysteine (Cys) found in RB-OPD. • The probe is used for monitoring exogenous and endogenous NO in living cells. [ABSTRACT FROM AUTHOR]

Abstract Hydrogen sulfide (H 2 S) has been considered to be involved in cytoprotective processes and redox signaling. It is very meaningful to track and analyze it in mitochondria. Herein, we report a novel "turn-on" mitochondria-targeting near-infrared fluorescent probe (Mito-NIR-SH) for detection of H 2 S in living cells, which was designed and synthesized by introducing 2,4-dinitrophenyl as fluorescence quenching group and H 2 S response moiety into Changsha near-infrared fluorophore (CS-OH). The structure of the fluorophore and the probe were characterized by 1H NMR, 13C NMR and mass spectrometry. Meanwhile, Mito-NIR-SH could quantitatively detect H 2 S at concentrations ranging from 0 to 30 μM with a detection limit as low as 89.3 nM, showing good chemical stability, fast "turn-on" response, selectively mitochondrial location, as well as high sensitivity and selectivity toward H 2 S. Based on this, it was successfully applied to imaging exogenous and endogenous H 2 S in living HeLa cells via confocal fluorescence microscopy. Graphical abstract fx1 Highlights • A novel chemically stable mitochondrial-targeting NIR probe has been synthesized. • Fast response to H 2 S with a large turn-on NIR fluorescence signal. • Located in mitochondria with high colocalization coefficient. • Image endogenous and exogenous H 2 S in live cells. [ABSTRACT FROM AUTHOR]

Abstract A new fluorescent probe was designed and synthesized according to the photo-induced electron transfer theory (PET) and the results of density functional theory calculation. The synthesized probe had a larger Stokes shift (130 nm) and double emission peak in response to highly toxic thiophenols, which could be applied in rapid and high sensitive detection of thiophenol in aqueous solution. A 25-fold fluorescence intensity enhancement was achieved and the fluorescent intensity at 460 nm had a linear relationship to the thiophenol in concentration range of 0–2.0 μM. Furthermore, a remarkable detection limit (6 nM) could be achieved. 50-fold other species have no interference to the detection. The practical utility of the probe was demonstrated by live HeLa cells imaging and thiophenol detection in real water samples. In linear range of 0–2.0 μM, the probe showed good recoveries (from 95% to 108%) for thiophenol detection in natural water samples. This method possesses high sensitivity, lower detection limit and fast response (i.e., 10 min, which is shorter than the average time response of other reported methods), indicating that the synthesized probe would be promising for real-time detection of thiophenols. Graphical abstract fx1 Highlights • DFT calculations were used to design a thiophenol sensor and understand the mechanism. • A novel double emission fluorescent probe BIN-T was synthesized and characterized. • BIN-T possesses high fluorescence quantum yield and fast response to thiophenol. • The probe can be applied in thiophenol assay in real water samples and bioimaging. [ABSTRACT FROM AUTHOR]

Abstract Anterior gradient protein 2 homolog (AGR) is a potential tumor biomarker and plays an important role in tissue development and regeneration. The intracellular detection of AGR is rarely reported. By conjugating the AGR aptamer with a cytosine base sequence as Ag cluster template, a highly fluorescent probe (MA@AgNCs) was synthesized for targeting intracellular AGR. The MA@AgNCs display a maximum fluorescence peak at 565 nm, and possess an excellent quantum yield (QY = 87.43%), small size, great biocompatibility, low toxicity, and good stability. Moreover, the as synthesized MA@AgNCs show high specificity on recognizing breast cancer cells. Graphical abstract Scheme 1 The sketch of synthesis process and fluorescence cell imaging. fx1 Highlights • The MA@AgNCs shows high quantum yield, excellent stability, and good thermostability with negligible cytotoxicity. • The MA@AgNCs imaged the AGR protein in MCF-7 cells with good selectivity between MCF-7 and Hela cells. [ABSTRACT FROM AUTHOR]

Abstract In this study, we have developed a facile, rapid one-pot strategy for synthesis of orange fluorescent gold nanoclusters (MBISA–AuNCs) at room temperature by using 2-Mercapto-5-benzimidazolesulfonic acid (MBISA) as both reducing and protecting reagent. The prepared AuNCs exhibited prominent advantages including high fluorescent quantum yield, good water solubility, excellent biocompatibility and low toxicity. Based on these superior properties, the AuNCs have been multi-talented applied in cell imaging, hydrogen sulfide detection and pH sensing. Confocal fluorescence imaging showed that the MBISA–AuNCs could enter living cells and distribute in the cytoplasm. Additionally, the obtained AuNCs could visualize H 2 S fluctuations in living cells without interference of autofluorescence based on their high sensitivity and selectivity detection for H 2 S with a linear range of 2.7 × 10–11–8.5 × 10−4 M and a detection limit of 0.024 nM. Most strikingly, the AuNCs exhibited strong pH dependent behavior and responded linearly, rapidly and reversibly to minor pH fluctuations within the range of 2.01–12.00. Therefore, the AuNCs could also image pH fluctuations in live cells with negligible autofluorescence and provided a new method of analysis to visualize monitoring wide pH range change in live cells. Graphical abstract The novel MBISA protected fluorescent gold nanoclusters have been successfully obtained by a facile, rapid one-pot synthesis method with a short time of 30 min. The AuNCs have been multi-talented applied in cell imaging, hydrogen sulfide detection and pH sensing. fx1 Highlights • A novel fluorescent gold nanoclusters were obtained by a facile, rapid one-pot synthesis method with short time of 30 min. • As-prepared AuNCs showed not only high fluorescence quantum yield but also low cytotoxicity and superior biocompatibility. • Novel fluorescent sensors have been successfully constructed for hydrogen sulfide detection and pH sensing. [ABSTRACT FROM AUTHOR]