Co-reporter:Longwei He, Xueling Yang, Kaixin Xu, and Weiying Lin
Analytical Chemistry September 5, 2017 Volume 89(Issue 17) pp:9567-9567
Publication Date(Web):August 9, 2017
DOI:10.1021/acs.analchem.7b02649
Biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play a crucial role in many physiological processes. Cys production and metabolism is closely connected with Hcy and GSH; meanwhile, the dynamic antioxidant defenses network by Cys is independent of the GSH system, and Cys can serve as a more effective biomarker of oxidative stress. Hence, it is significant and urgent to develop an efficient method for specific detection of Cys over other biothiols (Hcy/GSH). However, most of the present Cys-specific fluorescent probes distinguished Cys from Hcy through response time, which would suffer from an unavoidable interference from Hcy in long-time detection. In this work, in order to improve the selectivity, we employed an improved aromatic substitution–rearrangement strategy to develop a ratiometric Cys-specific fluorescent probe (Cou–SBD-Cl) based on a new fluorescence resonance energy transfer (FRET) coumarin–sulfonyl benzoxadiazole (Cou–SBD) platform for discrimination of Hcy and GSH. Response of Cou–SBD-Cl to Cys would switch FRET on and generate a new yellow fluorescence emission with a 56.1-fold enhancement of ratio signal and a 99 nm emission shift. The desirable dual-color ratiometric imaging was achieved in living cells and normal zebrafish. In addition, probe Cou–SBD-Cl was also applied to real-time monitor Cys fluctuation in lipopolysaccharide-mediated oxidative stress in zebrafish.
Co-reporter:Xuezhen Song;Baoli Dong;Xiuqi Kong;Chao Wang;Nan Zhang
Analytical Methods (2009-Present) 2017 vol. 9(Issue 12) pp:1891-1896
Publication Date(Web):2017/03/22
DOI:10.1039/C7AY00155J
Cysteine (Cys) is one of the important semi-essential amino acids, which often participates in many enzymatic reactions and has lots of biological functions. Herein, we present a sensitive and selective red fluorescent probe (RCys) for detecting Cys in living cells and animals. RCys utilized a rhodamine derivative as the fluorescent platform, and employed acrylate as the response site for Cys. When RCys responded to Cys, a significant turn-on red fluorescence at 638 nm was observed. RCys displayed obvious fluorescence response to Cys in a short time, and exhibited favorable selectivity to Cys over other thiols including GSH and Hcy. The biological applications demonstrated that RCys can be applied for the imaging of Cys in living cells and animals.
Co-reporter:Hua Chen;Yonghe Tang;Huiming Shang;Xiuqi Kong;Rui Guo
Journal of Materials Chemistry B 2017 vol. 5(Issue 13) pp:2436-2444
Publication Date(Web):2017/03/29
DOI:10.1039/C7TB00174F
Full-color fluorescence imaging, which utilizes multiple fluorescent imaging agents with emission covering the whole visible spectrum in the same specimen, is a powerful approach to study molecular processes in living systems. To achieve two-photon full-color bioimaging, two-photon full-color-tunable fluorescent materials (with emission from the blue to near-infrared region) are highly desirable. Herein, in this work, we outline the rational design, synthesis, optical property studies, and biological imaging studies of a unique family of two-photon full-color-tunable functional fluorescent materials. Based on the proposed “hybridization” strategy, we judiciously engineered the first family of two-photon full-color-tunable functional fluorescent materials (TPFC) and their lysosome-targetable derivatives (TPFC-Lyso). The novel TPFC dyes display two-photon full-color-tunable fluorescence emission from the blue to near-infrared region in solutions. By exploiting their unprecedented two-photon full-color-tunable properties, the new TPFC dyes were successfully applied for two-photon full-color imaging in living cells, and in particular, in living tissues at different penetration depths for the first time. In addition, as representative cases, we have described the first report of two-photon full-color fluorescence imaging in subcellular organelles, lysosomes, using the novel lysosome-targetable TPFC-Lyso dyes.
Co-reporter:Yong Liu;Fangfang Meng;Jing Nie;Jie Niu;Xiaoqiang Yu
Journal of Materials Chemistry B 2017 vol. 5(Issue 24) pp:4725-4731
Publication Date(Web):2017/06/22
DOI:10.1039/C7TB00979H
The cell membranal liquid-ordered (Lo) phase can control the structure and function of cell membranes. In this study, we have engineered a novel two-photon (TP) fluorescent probe, TP-HVC18, which remarkably displayed two different fluorescence emission profiles in the aggregate and solution states in distinct polar environments. In accordance with its aggregate fluorescence, TP-HVC18 also can emit a red fluorescence signal in Lo phase vesicles. Taking advantage of this unique feature, we have demonstrated that the new TP probe TP-HVC18 is suitable for imaging membranal Lo phase by an aggregate fluorescence method. Furthermore, the robust probe also exhibited uncontinuous red fluorescence distribution in the cell membranal Lo phase. Based on this intriguing character, we also successfully showed that the novel probe can be employed to exhibit uncontinuous distribution of cell membranal Lo phase by a 3D imaging technique. We expect that this aggregation-based fluorescent platform may be extended for the development of a wide variety of TP fluorescent probes for detecting several biological species.
Co-reporter:Mingguang RenBeibei Deng, Kai Zhou, Xiuqi Kong, Jian-Yong Wang, Weiying Lin
Analytical Chemistry 2017 Volume 89(Issue 1) pp:
Publication Date(Web):December 7, 2016
DOI:10.1021/acs.analchem.6b04385
Mitochondria, as essential and interesting organelles within the eukaryotic cells, play key roles in a variety of pathologies, and its abnormalities are closely associated with Alzheimer’s disease (AD) and other diseases. Studies have shown that the abnormal of viscosity and concentration of hydrogen peroxide in mitochondria were all associated with AD. Accordingly, the detection of viscosity and hydrogen peroxide in mitochondria has attracted great attention. However, it remains a great challenge to explore a single probe, which can dual-detect the viscosity and H2O2 in mitochondria. Herein, in two ways to prevent the twisted internal charge transfer (TICT) process, we designed and sythesized the first dual-detection fluorescent probe Mito-VH that can visualize viscosity and H2O2 in mitochondria with different fluorescence signals in living cells.
Co-reporter:Dr. Keyin Liu;Dr. Xiuqi Kong;Yanyan Ma; Weiying Lin
Angewandte Chemie 2017 Volume 129(Issue 43) pp:13674-13677
Publication Date(Web):2017/10/16
DOI:10.1002/ange.201707518
AbstractCarbon monoxide (CO) is one of the most important gaseous signal molecules in biological systems. However, the investigation of the functions of CO in living organisms is restricted by the lack of functional molecular tools. To address this critical challenge, we present herein the rational design, synthesis, and in vivo imaging studies of a powerful two-photon excited near-infrared fluorescent probe (1-Ac) for endogenous CO monitoring. The advantageous features of the new probe include high stability, low background fluorescence, large fluorescence enhancement, high sensitivity, and two-photon excitation with emission in the near-infrared region. Significantly, these merits of the probe enable the tracking of endogenous CO in zebrafish embryos and mouse tissues for the first time.
Co-reporter:Fangfang Meng, Yong Liu, Jie Niu, Weiying Lin
Tetrahedron Letters 2017 Volume 58, Issue 33(Issue 33) pp:
Publication Date(Web):16 August 2017
DOI:10.1016/j.tetlet.2017.07.030
Fluorescent dyes with large Stokes shift play a key role in avoiding self-quenching and scattered light of dyes in the process of biological imaging. In this work, a novel mitochondria-targetable fluorescent dye (PI-C2) with large Stokes shift (e. g. Maximum value is 219 nm in DMSO) have been developed. Compared to the commercial mitochondria probes MTR and MTG (Less than 30 nm in various solution), the newly constructed PI-C2 has a much larger Stokes shift in various solutions (169–219 nm in various solutions). Furthermore, the probe can successfully be applied for sensing mitochondria, and exhibited excellent photostability in different living cell lines. The novel fluorescent platform with the large Stokes may be extended to construct powerful fluorescent probes with large Stokes shift for detecting a wide variety of biomolecules in mitochondria.In this work, we developed a novel mitochondria-targetable fluorescent probe (PI-C2) with large Stokes shift. The newly constructed PI-C2 has a much larger Stokes shift in various solutions than the commercial mitochondria probes MTR and MTG.Download high-res image (89KB)Download full-size image
Co-reporter:Xiuqi Kong, Baoli Dong, Nan Zhang, Chao Wang, Xuezhen Song, Weiying Lin
Talanta 2017 Volume 174(Volume 174) pp:
Publication Date(Web):1 November 2017
DOI:10.1016/j.talanta.2017.06.023
•A red-emitting two-photon and tumor-specific fluorescent probe has been constructed.•The probe exhibits remarkable tumor-specificity with red emission.•The high-definition 3D imaging has been achieved in living tumor tissues.Tumor-specific imaging can provide an attractive approach for the early detection and prognosis of cancer, as well as the precise image-guided tumor-removal surgery. Herein, we describe a unique red-emitting two-photon fluorescent probe (N-BN) for tumor-specific imaging. N-BN utilized Nile Red as the red-emitting two-photon fluorophore and employed biotin as the tumor-specific ligand. In the presence of a variety of biomolecules or in different pH buffers, the fluorescence intensity of N-BN at 655 nm showed no noticeable change. N-BN exhibited the remarkable two-photon absorption cross sections of 15.4 g under excitation at 800 nm. Under the guidance of biotin, N-BN can be applied for the imaging of biotin-receptor positive cancer cells over biotin-negative cells under red-emitting one- and two-photon manners. Assisted by high-definition three-dimensional imaging, the living tumor tissues loaded with N-BN could display strong red two-photon fluorescence with a penetration depth of about 90 µm. Moreover, the in vivo and ex vivo imaging studies intuitively revealed that N-BN could track the tumor with highly tumor-specific property by a near-infrared manner.Download high-res image (202KB)Download full-size image
Co-reporter:Beibei Deng, Mingguang Ren, Jian-Yong Wang, Kai Zhou, Weiying Lin
Sensors and Actuators B: Chemical 2017 Volume 248(Volume 248) pp:
Publication Date(Web):1 September 2017
DOI:10.1016/j.snb.2017.03.135
•Fast response to H2S with a large turn-on fluorescence signal.•Image exogenous and endogenous H2S in living cells.•Localized in Mitochondria with a high colocalization coefficient.•Imaging H2S in living tissues with deep tissue penetration.Hydrogen sulfide (H2S), as signaling molecule, plays a crucial role in many biological processes in living organisms. At the organelle level, we need to study tools to explain the complexity of physiological H2S in mitochondria. Toward this goal, we have developed a new example of a fast responsive and mitochondrial-targeted two-photon fluorescent H2S probe (MT-HS) with a large turn-on fluorescence signal (40-fold fluorescence enhancement). The addition of H2S to MT-HS results a dramatic fluorescence enhancement around 540 nm. The probe could image exogenous and endogenous H2S in living cells and the probe was located in mitochondria with high colocalization coefficient compared with Mitochondrial-Tracker. The large fluorescence enhancement of the two-photon probe MT-HS renders it attractive for imaging H2S in living tissues with deep tissue penetration.Download high-res image (131KB)Download full-size image
Co-reporter:Jing Nie, Yong Liu, Jie Niu, Zhonghai Ni, Weiying Lin
Journal of Photochemistry and Photobiology A: Chemistry 2017 Volume 348(Volume 348) pp:
Publication Date(Web):1 November 2017
DOI:10.1016/j.jphotochem.2017.08.008
•Pyrene-based fluorophore as a novel fluorescent dye for developing a fluorescent probe Py-Boe with large Stokes shift in various solutions.•The probe Py-Boe is capable of concurrently high sensitive and selective detecting H2O2 in aqueous solution.•The probe Py-Boe is capable of detecting exogenous and endogenous H2O2 in mitochondria of living RAW 264.7 cellsHydrogen peroxide (H2O2) plays an important role in signal transduction and therapy of serious diseases. In this work, we have developed a new pyrene-based fluorescent probe Py-Boe, which possesses large Stokes shift and achieves detection of H2O2 in aqueous solution. The probe Py-Boe exhibits excellent photostability, high sensitive and selectivity. Taking advantage of these properties, the probe Py-Boe achieves succussfully imaging of exogenous and endogenous H2O2 in living RAW 264.7 cells. We expect that this dye with large Stokes shift may open an avenue to construct novel fluorescent probe with large Stokes shift for biological application.Herein, we have developed a new pyrene-based fluorescent probe Py-Boe with large Stokes shift and achieved high sensitive detection of H2O2 in aqueous solution. Furthermore, the probe Py-Boe is suitable for detecting exogenous and endogenous H2O2 in living RAW 264.7 cells.Download high-res image (131KB)Download full-size image
Co-reporter:Xi Dai, Xiuqi Kong, Weiying Lin
Dyes and Pigments 2017 Volume 142(Volume 142) pp:
Publication Date(Web):1 July 2017
DOI:10.1016/j.dyepig.2017.03.045
•The probe could determinate Cys in PBS buffer solution within 5 min.•Stokes shift of the probe reached 130 nm.•The probe has been applied for thiols in tissue imaging by two-photon excitation.Cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), the small molecule biological thiols, play essential roles in maintaining human biological systems. Research of quantitative determination of biothiols is always significant. We have designed and synthesized a fluorescent probe ANBI based on a naphthalene-benzo[g]indol-1-ium scaffold, quick respond to biothiols in water. The probe exhibits high stability, high selectivity, good water solubility and biocompatibility. Upon addition of biothiols, notably, probe ANBI showed an intense fluorescence within 5 min and displayed a large Stokes shift of 130 nm (Ex = 460 nm, Em = 590 nm). From the linear relationship of absorbance and intensity vs concentrations of Cys, it was determined that the limits of detection are 2.3 μM and 0.35 μM. Therefore, ANBI can qualitatively and quantitatively detect Cys by spectrometry in biological samples. Successfully, probe ANBI has been applied for biothiols in living HeLa cells by one- and two-photon excitation. Furthermore, we obtain the two-photon excited fluorescence images of ANBI in liver tissues and tumor tissues.Download high-res image (159KB)Download full-size image
Co-reporter:Xueling Yang, Longwei He, Kaixin Xu, Weiying Lin
Analytica Chimica Acta 2017 Volume 981(Volume 981) pp:
Publication Date(Web):15 August 2017
DOI:10.1016/j.aca.2017.05.016
•A fluorescent dyad (CS-NBD) was developed for efficiently discriminating Cys/Hcy from GSH and H2S.•Probe CS-NBD generates two different sets of fluorescence signal in two emission bands responding to Cys/Hcy and GSH/H2S.•Probe CS-NBD was employed to distinguish Cys and Hcy in living cells by dual-color fluorescence imaging.Biothiols, as reactive sulfur species (RSS), play important roles in human physiology, and they have a close connection of generation and metabolism pathways among of them. It is challenging to discriminate biothiols from each other due to the similar chemical structures and properties of them. Herein, we develop a fluorescent hybrid dyad (CS-NBD) for efficiently discriminating cysteine (Cys)/homocysteine (Hcy) from glutathione (GSH) and hydrogen sulfide (H2S) by a dual-channel detection method. CS-NBD performs inherently no fluorescence in ranging from visible to near infrared region. However, upon addition of Cys (2–150 μM)/Hcy (2–200 μM), CS-NBD generates significant fluorescence enhancement in two distinct emission bands (Green-Red), while encounter of GSH (2–100 μM) or H2S (2–70 μM) induces the fluorescence increase only in the red channel. The detection limit was determined to be 0.021 μM for Cys, 0.037 μM for Hcy, 0.028 μM for GSH, and 0.015 μM for H2S, respectively (S/N = 3). The interval distance between two emission bands is up to 163 nm, which is favourable to acquire the accurate data in measurement due to the reducing of crosstalk signals. CS-NBD is also successfully applied to distinguish Cys/Hcy in cellular context by dual-color fluorescence imaging.Download high-res image (199KB)Download full-size image
Co-reporter:Fangfang Meng;Yong Liu;Jie Niu
RSC Advances (2011-Present) 2017 vol. 7(Issue 26) pp:16087-16091
Publication Date(Web):2017/03/09
DOI:10.1039/C7RA00661F
Fluorescent dyes with large Stokes shifts play a key role in developing multi-purpose fluorescent probes for a wide variety of targets. In this study, we developed two novel alkyl chain-based fluorescent probes (CA-C12 and CA-C2) with large Stokes shifts. The alkyl chain length of the probes affect the membrane permeability, and hence both probes can be successfully applied for sensing the cell membrane and mitochondria in different living cell lines. Furthermore, the probes CA-C12 and CA-C2 exhibited large Stokes shifts and excellent photostability in the different cell lines. The fluorescent dyes with large Stokes shifts were expected to have broader applications for developing various fluorescent probes with excellent optical properties.
Co-reporter:Xuezhen Song;Baoli Dong;Xiuqi Kong;Chao Wang;Nan Zhang
RSC Advances (2011-Present) 2017 vol. 7(Issue 26) pp:15817-15822
Publication Date(Web):2017/03/09
DOI:10.1039/C7RA01479A
Hydrogen sulfide (H2S) could induce the proliferation of cancer cells in a concentration-dependent manner, and has close relation with the tumor growth. Monitoring the H2S level in real-time is of great important for understanding its roles in the cancer cell proliferation and the diagnosis of the tumor. Herein, a novel cancer cell-specific two-photon fluorescent probe BN-H2S for detecting H2S in cancer cells was designed and synthesized. Biotin was selected as the cancer cell-specific group and the azide group was employed as the response site for H2S. When BN-H2S responded to H2S, a turn-on fluorescence at 544 nm was observed clearly. BN-H2S exhibited high selectivity for H2S over other relative species. Under the guidance of the biotin group, BN-H2S can be successfully used for the two-photon imaging of H2S in cancer cells, while BN-H2S showed relatively weak response for H2S in normal cells. We expect that this design concept can be further developed for selectively detecting other biomolecules in living cancer cells.
Co-reporter:Kai Zhou;Mingguang Ren;Beibei Deng
New Journal of Chemistry (1998-Present) 2017 vol. 41(Issue 20) pp:11507-11511
Publication Date(Web):2017/10/09
DOI:10.1039/C7NJ02270K
Using hemicyanine and carbazole as an acceptor and a donor, respectively, we designed and synthesized two new mitochondrial-targeted fluorescent viscosity probes (MHC-V1 and MHC-V2). The new probes were membrane-permeable and suitable for visualization of the changes of viscosity within the mitochondria of living cells.
Co-reporter:Yong Liu;Jie Niu;Jing Nie;Fangfang Meng
New Journal of Chemistry (1998-Present) 2017 vol. 41(Issue 9) pp:3320-3325
Publication Date(Web):2017/05/02
DOI:10.1039/C7NJ00107J
Fluorescent probes with large Stokes shifts play a key role in maintaining the accuracy of biological imaging and minimizing the self-quenching effect. In this work, we have developed a novel fluorescent probe CAI, which possessed a large Stokes shift in various solutions. We found that CAI was capable of detecting hydrogen peroxide (H2O2) in aqueous solution. Furthermore, probe CAI can sense exogenous and endogenous H2O2 in the mitochondria of living RAW 264.7 cells. In addition, probe CAI exhibited ideal properties such as excellent photostability, high sensitivity and selectivity. This fluorescent dye with a large Stokes shift was expected to have a more broad range of applications for developing various fluorescent probes with large Stokes shifts.
Co-reporter:Mingguang Ren;Jing Nie;Beibei Deng;Kai Zhou;Jian-Yong Wang
New Journal of Chemistry (1998-Present) 2017 vol. 41(Issue 13) pp:5259-5262
Publication Date(Web):2017/06/26
DOI:10.1039/C7NJ00949F
We have developed a new lysosome-targeting ratiometric fluorescent probe (FL-HA) for specific determination of HOCl in living cells. The developed probe exhibits accurate lysosome-targeting ability, good signal resolution, and high selectivity. Moreover, fluorescence imaging shows that FL-HA could be used as a probe for ratiometric visualization of exogenous and endogenous HOCl in lysosomes with a high colocalization coefficient compared with a commercial lysosomal location dye.
Co-reporter:Baoli Dong;Xuezhen Song;Xiuqi Kong;Chao Wang;Nan Zhang
Journal of Materials Chemistry B 2017 vol. 5(Issue 5) pp:988-995
Publication Date(Web):2017/02/01
DOI:10.1039/C6TB02957D
Lysosomal pH is closely related to the metastasis and apoptosis of cancer cells. Detecting lysosomal pH changes in cancer cells could be helpful for analyzing tumor progressions and in-depth study of the roles of lysosomes in tumor invasion and metastasis. Herein, we describe a novel tumor-targeting and lysosome-specific two-photon fluorescent probe (BN-lys) for imaging pH changes for the first time. Biotin was employed as the tumor-targeting module, and morpholine was selected as the lysosome-specific group and the pH site to control the fluorescence by photoinduced electron transfer (PET) mechanism. With a pKa value of 5.36, BN-lys showed a fast and reversible fluorescence response to pH. Under the guidance of the biotin group, BN-lys displayed strong one-photon and two-photon fluorescence responses to lysosomal pH in cancer cells, while it displayed weak fluorescence in normal cells. Furthermore, BN-lys could be applied for the imaging of chloroquine-stimulated lysosomal pH changes in living cells. These features demonstrate that this probe could have practical applications in biological research.
Co-reporter:Baoli Dong;Xuezhen Song;Xiuqi Kong;Chao Wang;Nan Zhang
Journal of Materials Chemistry B 2017 vol. 5(Issue 26) pp:5218-5224
Publication Date(Web):2017/07/04
DOI:10.1039/C7TB00703E
Nitroxyl (HNO) plays important roles in the regulation of many physiological and pathological processes, and can serve as a potential therapeutic agent for cardiovascular disease. The development of HNO detection in living systems is greatly important for in-depth studies of its biosynthesis and activities. Herein, we describe a novel two-photon red-emissive fluorescence probe (RP) for imaging HNO in living cells and tissues. RP was based on a red-emissive dye, Rho, and showed no fluorescence. When responding to HNO, RP can emit red fluorescence with the emission wavelength at 638 nm. RP exhibited a sensitive and selective response to HNO. Theoretical calculations demonstrated that the overlaps between the HOMO and LUMO were large for Rho and tiny for RP, consistent with the absorption and fluorescence properties of Rho and RP. Assisted by three-dimensional (3D) imaging, the two-photon imaging of HNO with red emission color in living tissues was successfully performed.
Co-reporter:Jian-Yong Wang;Zhan-Rong Liu;Mingguang Ren;Xiuqi Kong
Journal of Materials Chemistry B 2017 vol. 5(Issue 1) pp:134-138
Publication Date(Web):2016/12/21
DOI:10.1039/C6TB02610A
Cysteine (Cys), a small-molecule aminothiol, plays important roles in various physiological processes in connection with various diseases, such as skin lesions, edema, hair depigmentation and liver damage. We developed a novel two-photon fluorescent probe for sensing Cys in presence of GSH and Hcy in vivo. The two-photon fluorescent probe exhibited favorable properties, including fast response (about 20 min), good selectivity, and low cytotoxicity. Furthermore, it was successfully applied for imaging Cys in living cells and tissues.
Co-reporter:Mingguang Ren;Beibei Deng;Kai Zhou;Jian-Yong Wang;Xiuqi Kong
Journal of Materials Chemistry B 2017 vol. 5(Issue 10) pp:1954-1961
Publication Date(Web):2017/03/08
DOI:10.1039/C6TB03388A
Nitroxyl plays crucial roles in many biological pathways and can serve as a potent therapeutic agent for the treatment of heart failure. Recent studies suggest that HNO may be produced in mitochondria and the HNO formed might have functional consequences for mitochondrial activity. However, in order to study the function of HNO in mitochondria, a suitable research method is needed. Herein, through rational design, we synthesized a new mitochondria-targeted fluorescent nitroxyl probe (Mito-HNO). The developed probe was highly selective toward HNO over other reactive nitrogen species and reducing species. In addition, the probe Mito-HNO was rapidly responsive and suitable for visualization of HNO in mitochondria in living cells. The probe is expected to be employed in further revealing the biological function of HNO in subcellular mitochondria.
Co-reporter:Keyin Liu;Huiming Shang;Xiuqi Kong
Journal of Materials Chemistry B 2017 vol. 5(Issue 21) pp:3836-3841
Publication Date(Web):2017/05/31
DOI:10.1039/C7TB00187H
Biothiols such as cysteine (Cys) and glutathione (GSH) are important reductive species that are widely spread in the liver, heart, brain and so on, and are essential for maintaining the fundamental roles of these organs. Fluorescence detection of biothiols in living organisms is of great importance for exploring the metabolic pathways and physiological function in living organisms. Most of the near-infrared probes for biothiols have small Stokes shifts, usually less than 50 nm, which greatly hamper their applications in biological imaging; herein, a novel fluorescent CS-thiol probe based on a Changsha (CS) near-infrared dye analogue with a large Stokes shift was developed and applied for live animal imaging. In the presence of biothiols, such as Cys, CS-thiols show a broad fluorescence emission at 660 nm and exhibit high selectivity toward biothiols among other amino acids and reactive species. CS-Thiols exhibited little toxicity to HeLa cells and were successfully applied to image biothiols in living cells and living animals.
Co-reporter:Yong Liu;Jie Niu;Weishan Wang;Baoli Dong
Journal of Materials Chemistry B 2017 vol. 5(Issue 38) pp:7801-7808
Publication Date(Web):2017/10/04
DOI:10.1039/C7TB02148H
Very recently, aggregation-induced emission (AIE) and two-photon (TP) emission materials have attracted great attention owing to their widespread applications. Herein, interestingly, we described a unique single fluorophore core with different substituents that can show either outstanding AIE or TP fluorescence properties. The introduction of an electron donating unit such as a tertiary amine group on the phenanthrenequinone imidazole core afforded a novel AIE-based fluorescent material PIN. The optical studies of PIN revealed that appropriate structural modifications on the phenanthrenequinone imidazole core could result in AIE character. On the other hand, modification of an electron-withdrawing moiety such as an indolium moiety on the same phenanthrenequinone imidazole-core provided a new material PID, which exhibited favorable TP emission, indicating that phenanthrenequinone imidazole derivatives could be exploited as TP materials. Furthermore, we have demonstrated that the novel AIE or TP materials constructed herein can be successfully applied for sensing targets of interest in aqueous and biological settings owing to their highly desirable emission profiles. The intriguing finding that careful modification of the phenanthrenequinone imidazole scaffold could afford excellent AIE or TP materials may open a new avenue to engineer robust materials with diverse properties based on a versatile core for various applications.
Co-reporter:Longwei He;Xueling Yang;Kaixin Xu
Chemical Communications 2017 vol. 53(Issue 29) pp:4080-4083
Publication Date(Web):2017/04/06
DOI:10.1039/C7CC00512A
The mitochondria-targeted turn-on fluorescent probe (Mito-FMP) based on a benzoxadiazole platform was developed for detection of malondialdehyde (MDA). Mito-FMP performed with large enhancement of the optical signal (774-fold) in response to MDA in an aqueous system and has the capability of monitoring endogenous MDA in HeLa cells and onion tissues.
Co-reporter:Longwei He;Xueling Yang;Kaixin Xu;Xiuqi Kong
Chemical Science (2010-Present) 2017 vol. 8(Issue 9) pp:6257-6265
Publication Date(Web):2017/08/21
DOI:10.1039/C7SC00423K
Biothiols, which have a close network of generation and metabolic pathways among them, are essential reactive sulfur species (RSS) in the cells and play vital roles in human physiology. However, biothiols possess highly similar chemical structures and properties, resulting in it being an enormous challenge to simultaneously discriminate them from each other. Herein, we develop a unique fluorescent probe (HMN) for not only simultaneously distinguishing Cys/Hcy, GSH, and H2S from each other, but also sequentially sensing Cys/Hcy/GSH and H2S using a multi-channel fluorescence mode for the first time. When responding to the respective biothiols, the robust probe exhibits multiple sets of fluorescence signals at three distinct emission bands (blue-green-red). The new probe can also sense H2S at different concentration levels with changes of fluorescence at the blue and red emission bands. In addition, the novel probe HMN is able to discriminate and sequentially sense biothiols in biological environments via three-color fluorescence imaging. We expect that the development of the robust probe HMN will provide a powerful strategy to design fluorescent probes for the discrimination and sequential detection of biothiols, and offer a promising tool for exploring the interrelated roles of biothiols in various physiological and pathological conditions.
Co-reporter:Huiming Shang;Keyin Liu
Analytical Methods (2009-Present) 2017 vol. 9(Issue 25) pp:3790-3794
Publication Date(Web):2017/06/30
DOI:10.1039/C7AY01113J
Sulfur dioxide (SO2) is one of the most important reactive sulfur species widely found in living organisms. SO2 is recognized as an important regulatory factor that can modulate the cardiovascular system, with functions such as relaxing blood vessels, lowering blood pressure and acting as an anti-oxidation. Compared to fluorescence turn-on type probes, a ratiometric fluorescent probe can avoid the background fluorescence of the probe and the interference from other environmental factors. Herein, a new ratiometric-type fluorescent probe with emission in the near infrared area was developed. Upon interaction with SO2, the emission at 750 nm decreased and a new fluorescent peak was observed in the visible region simultaneously. The novel probe showed excellent selectivity toward SO2 among other species. In addition, the new probe exhibited little toxicity to HeLa cells and was used for imaging SO2 in solution and the cell environment successfully with a fluorescence change in both the green and red channels.
Co-reporter:Longwei He;Xueling Yang;Kaixin Xu;Yunzhen Yang
Chemical Communications 2017 vol. 53(Issue 98) pp:13168-13171
Publication Date(Web):2017/12/07
DOI:10.1039/C7CC07296A
A novel multifunctional logic gate based on a triple-chromophore (coumarin–NBD–flavylium, CNF) fluorescent biothiol probe with diverse fluorescence signal patterns was rationally designed and synthetized. On the new triad CNF, diverse logic operations such as OR, TRANSFER, INH, NOT, and YES logic gates were achieved by using biothiols and fluorescence signal patterns as the multiple inputs and outputs, respectively.
Co-reporter:Chao Wang, Baoli Dong, Xiuqi Kong, Xuezhen Song, Nan Zhang, Weiying Lin
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2017 Volume 182(Volume 182) pp:
Publication Date(Web):5 July 2017
DOI:10.1016/j.saa.2017.03.058
•A cancer cell-specific fluorescent probe Rh-Cu for detecting Cu2 + was rationally designed and synthesized.•Rh-Cu exhibited excellent sensitivity and high selectivity for Cu2 + over the other relative species.•Rh-Cu can show obviously enhanced fluorescence in response to Cu2 + in cancer cells, while it showed no marked response to Cu2 + in normal cells.•When Rh-Cu responded Cu2 + in cancer cells, the enhanced red fluorescence can be observed clearly.Monitoring copper level in cancer cells is important for the further understanding of its roles in the cell proliferation, and also could afford novel copper-based strategy for the cancer therapy. Herein, we have developed a novel cancer cell-specific fluorescent probe for the detecting Cu2 + in living cancer cells. The probe employed biotin as the cancer cell-specific group. Before the treatment of Cu2 +, the probe showed nearly no fluorescence. However, the probe can display strong fluorescence at 581 nm in response to Cu2 +. The probe exhibited excellent sensitivity and high selectivity for Cu2 + over the other relative species. Under the guidance of biotin group, could be successfully used for detecting Cu2 + in living cancer cells. We expect that this design strategy could be further applied for detection of the other important biomolecules in living cancer cells.Download high-res image (270KB)Download full-size image
Co-reporter:Zhan-Rong Liu, Jian-Yong Wang, Mingguang Ren, Weiying Lin
Journal of Photochemistry and Photobiology A: Chemistry 2017 Volume 343(Volume 343) pp:
Publication Date(Web):15 June 2017
DOI:10.1016/j.jphotochem.2017.04.008
•A two-photon fluorescent probe was designed and synthesized for detection of aminothiols in vivo.•The probe had exhibited ideal properties including fast response (about 5 min), good selectivity, and low cytotoxicity.•The two-photon turn-on fluorescent probe could be employed to image aminothiols in the living cells and tissues.Aminothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play important roles in various physiological processes such as cancer, neuropathy, and cardiomyopathy. Herein, a two-photon fluorescent probe based on a naphthalene-benzothiazole platform was designed and synthesized for the detection of aminothiols in vivo. The probe exhibited excellent properties including fast response (about 5 min), good selectivity, and low cytotoxicity. The turn-on fluorescent probe could be employed to two-photon image aminothiols in living cells and tissues.Download high-res image (124KB)Download full-size image
Co-reporter:Huiming Shang, Hua Chen, Yonghe Tang, Yanyan Ma, Weiying Lin
Biosensors and Bioelectronics 2017 Volume 95(Volume 95) pp:
Publication Date(Web):15 September 2017
DOI:10.1016/j.bios.2017.04.017
•FR-TP represented the first far-red emissive two-photon fluorescent probe for specific detection of thiophenols.•The emission wavelength of the probe FR-TP is located in the far-red region when excited by the two-photon laser.•The novel probe FR-TP was employed to image thiophenols not only in living cells but also in living tissues.•FR-TP could be used to investigate thiophenol poisoning in the model of thiophenol inhalation by the two-photon microscope.Thiophenol is a highly toxic compound which is essential in the field of organic synthesis and drug design. However, the accumulation of thiophenols in the environment may cause serious health problems for human bodies ultimately. Therefore, it is critical to develop efficient methods for visualization of thiophenol species in biological samples. In this work, an innovative two-photon fluorescent turn-on probe FR-TP with far-red emission for thiophenols based on FR-NH2 fluorophore and 2,4-dinitrophenylsulfonyl recognition site was reported. The new probe can be used for thiophenol detection with large far-red fluorescence enhancement (about 155-fold), rapid response (completed within 100 s), excellent sensitivity (DL 0.363 μM), high selectivity, and lower cellular auto-fluorescence interference. Importantly, the probe FR-TP can be successfully employed to visualize thiophenols not only in the living HeLa cells but also in living liver tissues. In addition, through two-photon tissue imaging, the probe was used to monitor and investigate biological thiophenol poisoning in the animal model of thiophenol inhalation for the first time.
Co-reporter:Hua Chen, Yonghe Tang, Mingguang Ren and Weiying Lin
Chemical Science 2016 vol. 7(Issue 3) pp:1896-1903
Publication Date(Web):24 Nov 2015
DOI:10.1039/C5SC03591K
We describe a unique approach for the development of an interesting type of the fluorescent probes, which can show different modes of fluorescence signals to distinct concentration ranges of a target of interest. The key points for the design of the new type of the fluorescent probes include the judicious selection of the dye platforms and the corresponding high- and low-sensitivity sites. It is known that the normal concentrations of biological thiols have significant biological functions. However, up- or down-regulated concentrations of thiols may induce several diseases. Therefore, it is highly important to monitor the changes of thiol concentrations in living systems. Based on the proposed strategy, we engineer the novel NIR fluorescent probe, CHMC-thiol, which remarkably can display a turn-on signal to the low concentration range of thiols and a ratiometric response to the high concentration range of thiols for the first time. We anticipate that the intriguing strategy formulated herein will be widely useful for the development of concentration range-dependent fluorescent probes.
Co-reporter:Baoli Dong, Kaibo Zheng, Yonghe Tang and Weiying Lin
Journal of Materials Chemistry A 2016 vol. 4(Issue 7) pp:1263-1269
Publication Date(Web):24 Dec 2015
DOI:10.1039/C5TB02073E
Nitroxyl (HNO) is one of the important reactive nitrogen species (RNS) and show significant biological activities with significant therapeutic potential. Herein, three novel turn-on probes (NP-1–3) based on structurally related dyes with different emission colors as fluorescent scaffolds have been developed for detecting HNO in biological systems. The probes exhibit high sensitivity, excellent selectivity, desirable performance at physiological pH and low cytotoxicity. By incubating living cells with these probes simultaneously, we demonstrate the multicolor imaging of HNO with emission colors in the range of green to near-infrared (NIR) in living systems for the first time. Furthermore, probe NP-3 responds to HNO with a significant turn-on NIR fluorescence signal upon excitation in the NIR region, and it is successfully applied for sensing HNO in living mice.
Co-reporter:Mingguang Ren, Beibei Deng, Kai Zhou, Xiuqi Kong, Jian-Yong Wang, Gaoping Xu and Weiying Lin
Journal of Materials Chemistry A 2016 vol. 4(Issue 27) pp:4739-4745
Publication Date(Web):13 Jun 2016
DOI:10.1039/C6TB01085G
Hypochorous acid plays important roles in numerous physiological and pathological processes. At the cell organelle level, an abnormal concentration of hypochorous acid in the lysosomes causes redox imbalance and the loss of function of the lysosomes. Herein, the first small molecule based, lysosomal-targeted ratiometric fluorescent HOCl probe (Lyso-HA) was synthesized through a rational design. The new probe was highly selective toward HOCl over other reactive oxygen species and exhibits a large variation (up to 97-fold) in its fluorescence ratio (I585/I450), with good signal resolution. The probe Lyso-HA is membrane-permeable and is suitable for ratiometric visualization of exogenous and endogenous HOCl at lysosomes in living cells.
Co-reporter:Longwei He, Xueling Yang, Mingguang Ren, Xiuqi Kong, Yong Liu and Weiying Lin
Chemical Communications 2016 vol. 52(Issue 61) pp:9582-9585
Publication Date(Web):29 Jun 2016
DOI:10.1039/C6CC04254F
An ultra-fast illuminating fluorescent formaldehyde (FA) probe (R6-FA) was designed and synthesized, and it exhibited a significant response to both FA in aqueous solution and as a gas. We have employed R6-FA not only to image FA in living cells, but also to detect FA in dried shiitake mushrooms and indoors for the first time, indicating its broad potential applications for monitoring FA in living systems, the food industry, and the environment.
Co-reporter:Yong Liu, Fangfang Meng, Longwei He, Xiaoqiang Yu and Weiying Lin
Chemical Communications 2016 vol. 52(Issue 57) pp:8838-8841
Publication Date(Web):16 Jun 2016
DOI:10.1039/C6CC03746A
It is found that 2,7-substituted carbazole derivative HVC-6 possesses distinct luminescence features in both aggregate and solution states. In view of this, probe HVC-6 realizes highly sensitive detection of RNA in pure water systems by an aggregation–disaggregation method for the first time.
Co-reporter:Yong Liu, Fangfang Meng, Longwei He, Keyin Liu and Weiying Lin
Chemical Communications 2016 vol. 52(Issue 43) pp:7016-7019
Publication Date(Web):29 Apr 2016
DOI:10.1039/C6CC02368A
Herein, we have developed a novel dual-site two-photon fluorescent probe TP-PMVC as the first paradigm of the probes, which can concurrently report lysosomes and lysosomal H2S with two different sets of fluorescence signals in the living cells and tissues.
Co-reporter:Mingguang Ren, Beibei Deng, Xiuqi Kong, Kai Zhou, Keyin Liu, Gaoping Xu and Weiying Lin
Chemical Communications 2016 vol. 52(Issue 38) pp:6415-6418
Publication Date(Web):30 Mar 2016
DOI:10.1039/C6CC00966B
By blocking the intramolecular twisted internal charge transfer (TICT) process, we designed and sythesized the first TICT-based fluorescent probe for hydrogen sulfide. The new probe exhibits high selectivity, good membrane-permeability and is suitable for visualization of exogenous and endogenous hydrogen sulfide in living cells.
Co-reporter:Longwei He, Xueling Yang, Yong Liu, Xiuqi Kong and Weiying Lin
Chemical Communications 2016 vol. 52(Issue 21) pp:4029-4032
Publication Date(Web):08 Feb 2016
DOI:10.1039/C5CC09796G
We have described a ratiometric fluorescent formaldehyde probe (RFFP) based on the 6-hydroxy naphthalene chromophore for the first time. The probe is suitable for ratiometric detection of formaldehyde both in the solution and living biological samples with two distinct emission bands.
Co-reporter:Haitao Zhang, Xiuqi Kong, Yonghe Tang, and Weiying Lin
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 25) pp:16227-16239
Publication Date(Web):June 9, 2016
DOI:10.1021/acsami.6b03254
Currently, the development of polymeric micelles combining diagnosis and targeted therapy is theoretically and practically significant in cancer treatment. In addition, it has been reported that cancer cells can produce large amounts of hydrogen sulfide (H2S) and their survival depends on the content of H2S. In this study, a series of N-(2-hydroxyethyl)-4-azide-1,8-naphthalimide ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-poly(methyl methacrylate) (N3-Nap-PHEMA-b-PMMA-N3) micelles were prepared. Around cancer tissues, the N3-Nap-PHEMA45-b-PMMA42-N3 micelles exhibited dual characteristics of monitoring H2S and H2S triggered charge reversal with the reduction of the azido group. The surface charge of N3-Nap-PHEMA45-b-PMMA42-N3 micelles reversed from negative to positive after monitoring H2S. With H2S triggered charge reversal, the cellular uptake of DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles was effectively enhanced through electrostatic attraction mediated targeting, and a fast doxorubicin (DOX) release rate was observed. The MTT assay demonstrated that N3-Nap-PHEMA45-b-PMMA42-N3 micelles were biocompatible to HeLa cells, and DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles showed enhanced cytotoxicity in HeLa cells in the presence of H2S. Furthermore, in vivo fluorescence imaging and biodistribution experiments revealed that DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles could provide good tumor imaging and accumulate in tumor tissue. Therefore, N3-Nap-PHEMA45-b-PMMA42-N3 micelles can be used as a promising platform for tumor diagnosis and therapy.
Co-reporter:Baoli Dong, Xuezhen Song, Chao Wang, Xiuqi Kong, Yonghe Tang, and Weiying Lin
Analytical Chemistry 2016 Volume 88(Issue 7) pp:4085
Publication Date(Web):March 8, 2016
DOI:10.1021/acs.analchem.6b00422
Acidic pH is a critical physiological factor for controlling the activities and functions of lysosome. Herein, we report a novel dual site-controlled and lysosome-targeted intramolecular charge transfer–photoinduced electron transfer–Fluorescence resonance energy transfer (ICT–PET–FRET) fluorescent probe (CN-pH), which was essentially the combination of a turn-on pH probe (CN-1) and a turn-off pH probe (CN-2) by a nonconjugated linker. Coumarin and naphthalimide fluorophores were selected as donor and acceptor to construct the FRET platform. Hydroxyl group and morpholine were simultaneously employed as the two pH sensing sites and controlled the fluorescence of coumarin and naphthalimide units by ICT and PET, respectively. The sensing mechanism of CN-pH to pH was essentially an integration of ICT, PET, and FRET processes. Meanwhile, the morpholine also can serve as a lysosome-targeted group. By combining the two data analysis approaches of the ratios of the two emission intensities (R) and the reverse ratio R′ (R′ = 1/R), the fluorescent ratio of CN-pH can show proportional relationship to pH values in a very broad range from pH 4.0 to 8.0 with high sensitivity. The probe has been successfully applied for the fluorescence imaging of the lysosomal pH values, as well as ratiometrically visualizing chloroquine-stimulated changes of intracellular pH in living cells. These features demonstrate that the probe can afford practical application in biological systems.
Co-reporter:Yonghe Tang, Xiuqi Kong, Zhan-Rong Liu, An Xu, and Weiying Lin
Analytical Chemistry 2016 Volume 88(Issue 19) pp:9359
Publication Date(Web):September 21, 2016
DOI:10.1021/acs.analchem.6b02879
As one of the simplest reactive carbonyl species, formaldehyde is implicated in nervous system diseases and cancer. Organelles play crucial roles in various physiological processes in living cells. Accordingly, the detection of endogenous formaldehyde at the subcellular level is of high interest. We herein describe the development of the first organelle-targeted fluorescent formaldehyde probe (Na-FA-Lyso). The new probe exhibits favorable features including a large fluorescence enhancement (about 350-fold) and a fast response to formaldehyde. Significantly, the novel probe Na-FA-Lyso was employed to visualize the endogenous formaldehyde in the lysosomes in living cells for the first time.
Co-reporter:Beibei Deng, Mingguang Ren, Xiuqi Kong, Kai Zhou and Weiying Lin
RSC Advances 2016 vol. 6(Issue 67) pp:62406-62410
Publication Date(Web):22 Jun 2016
DOI:10.1039/C6RA12127F
Through an intramolecular nucleophilic substitution reaction and ESIPT mechanism, we designed and synthesized a fluorescent hydrogen sulfide probe with a large turn on fluorescence signal (400-fold). The new probe exhibits high selectivity, good membrane-permeability and is suitable for the visualization of exogenous and endogenous hydrogen sulfide in living cells.
Co-reporter:Yong Liu, Fangfang Meng and Weiying Lin
RSC Advances 2016 vol. 6(Issue 37) pp:30951-30955
Publication Date(Web):21 Mar 2016
DOI:10.1039/C6RA03313J
The selective detection of copper ions and cysteine has been very challenging, especially in pure water system. In this work, we have engineered a novel fluorescent probe PI, which remarkably can reversibly detect copper ions (Cu2+) and cysteine (Cys) in a pure water system. In addition, the time dependent fluorescence intensity changes of the probe PI revealed that the probe showed higher fluorescence intensity within 2 s in the presence of Cu2+ and Cys than in the presence of Cu2+. Furthermore, we demonstrated that this probe could effectively detect Cu2+ and Cys in living cells. The present study provided a unique strategy in which a single fluorescent probe detected multiple targets.
Co-reporter:Yong Liu, Fangfang Meng, Yonghe Tang, Xiaoqiang Yu and Weiying Lin
New Journal of Chemistry 2016 vol. 40(Issue 4) pp:3726-3731
Publication Date(Web):16 Feb 2016
DOI:10.1039/C5NJ02821C
Rapid monitoring and tracking of a trans membrane process and mitochondrial fission and fusion dynamics play critical roles in judging the occurrence and development of disease, and can give insights for studying apoptosis and cell degeneration. However, the existing probes are not capable of rapid monitoring and tracking the above dynamics process. To solve this problem, we develop a unique functional mitochondria probe containing long alkyl chains, 3,5-bis((E)-2-(pyridin-4-yl)vinyl)-1H-indole monoiodide (MT-PVIM), which is capable of rapid real-time imaging and tracking mitochondrial fission and fusion dynamics. In addition, compared with a commercially available mitochondrial probe MTR, the MT-PVIM probe has excellent specificity to mitochondria with outstanding tolerance of micro-environmental changes, thus representing a potential candidate as a tracking agent for apoptosis studies. The good performance of our proposed approach demonstrates that this strategy might open up new opportunities for the development of rapid image mitochondria-targetable molecular tools for bioanalytical and biomedical applications.
Co-reporter:Yonghe Tang;Dr. Xiuqi Kong;An Xu;Dr. Baoli Dong ; Weiying Lin
Angewandte Chemie International Edition 2016 Volume 55( Issue 10) pp:3356-3359
Publication Date(Web):
DOI:10.1002/anie.201510373
Abstract
Investigation of the physiological and pathological functions of formaldehyde (FA) are largely restricted by a lack of useful FA imaging agents, in particular, those that allow detection of FA in the context of living tissues. Herein, we present the rational design, synthesis, and photophysical property studies of the first two-photon fluorescent FA probe, Na-FA. Importantly, the highly desirable attributes of the probe Na-FA (such as a very large turn-on signal (up to 900-fold), a low detection limit, and a very fast onset imparted by the unique design aspects of the probe), make it possible to monitor endogenous FA in living tissues for the first time. Furthermore, sodium bisulfite was identified as a simple and convenient inhibitor of FA within biological environments.
Co-reporter:Yonghe Tang;Dr. Xiuqi Kong;An Xu;Dr. Baoli Dong ; Weiying Lin
Angewandte Chemie 2016 Volume 128( Issue 10) pp:3417-3420
Publication Date(Web):
DOI:10.1002/ange.201510373
Abstract
Investigation of the physiological and pathological functions of formaldehyde (FA) are largely restricted by a lack of useful FA imaging agents, in particular, those that allow detection of FA in the context of living tissues. Herein, we present the rational design, synthesis, and photophysical property studies of the first two-photon fluorescent FA probe, Na-FA. Importantly, the highly desirable attributes of the probe Na-FA (such as a very large turn-on signal (up to 900-fold), a low detection limit, and a very fast onset imparted by the unique design aspects of the probe), make it possible to monitor endogenous FA in living tissues for the first time. Furthermore, sodium bisulfite was identified as a simple and convenient inhibitor of FA within biological environments.
Co-reporter:Jian-Yong Wang, Zhan-Rong Liu, Mingguang Ren, Xiuqi Kong, Keyin Liu, Beibei Deng, Weiying Lin
Sensors and Actuators B: Chemical 2016 Volume 236() pp:60-66
Publication Date(Web):29 November 2016
DOI:10.1016/j.snb.2016.04.163
•A novel turn on fluorescent probe based on a hybrid carbazole-cyanine platform was designed and synthesized for detecting hydroxyl radicals in living cells.•The CCy-OH probe had exhibited ideal properties including fast response (0.5 min), good selectivity, and low cytotoxicity.•Almost 60-fold fluorescence enhancement was obtained when the probe was treated with OH in solution with excitation at 510 nm and emission at 604 nm.•Fluorescence imaging shows that the novel CCy-OH probe is membrane-permeable and suitable for detecting endogenous hydroxyl radicals in living cells.A novel turn on fluorescent probe based on a hybrid carbazole-cyanine platform was designed and synthesized for detecting hydroxyl radicals. The probe had exhibited ideal properties including fast response (0.5 min), good selectivity, and low cytotoxicity. Almost 60-fold fluorescence enhancement was obtained in the presence of OH in solution. The novel fluorescent probe could be employed to image endogenous hydroxyl radicals in living cells.A novel turn on fluorescent probe based on a hybrid carbazole-cyanine platform was designed and synthesized for detecting hydroxyl radicals. The probe had exhibited ideal properties including fast response (0.5 min), good selectivity, and low cytotoxicity. Almost 60-fold fluorescence enhancement was obtained in the presence of OH in solution. The novel fluorescent probe could be employed to image endogenous hydroxyl radicals in living cells.Figure optionsDownload full-size imageDownload as PowerPoint slide
Co-reporter:Mingguang Ren, Beibei Deng, Jian-Yong Wang, Xiuqi Kong, Zhan-Rong Liu, Kai Zhou, Longwei He, Weiying Lin
Biosensors and Bioelectronics 2016 Volume 79() pp:237-243
Publication Date(Web):15 May 2016
DOI:10.1016/j.bios.2015.12.046
•Fast response to H2O2 with a large turn-on fluorescence signal.•Imaging exogenous and endogenous H2O2 in living cells.•Localized in lysosomes with a high colocalization coefficient.•Imaging H2O2 in living tissues with deep tissue penetration.Hydrogen peroxide (H2O2) plays a crucial role in many biological processes in the human body. As our understanding of the complexity of physiological H2O2 in lysosome, investigative tools are required to make sense of this interconnectivity. Toward this goal, we have developed a new example of a fast responsive and lysosome-targeted two-photon H2O2 fluorescent probe (Lyso-HP) with a large turn-on fluorescence signal (80-fold fluorescence enhancement). The addition of H2O2 to Lyso-HP results a dramatic fluorescence enhancement around 550 nm. The probe could image exogenous and endogenous H2O2 in living cells and the probe was located in lysosomes with high colocalization coefficient (0.96) compared with LysoTracker. The large fluorescence enhancement of the two-photon probe Lyso-HP renders it attractive for imaging H2O2 in living tissues with deep tissue penetration. Significantly, the probe is feasible for fluorescently monitoring H2O2 level changes in lysosomes and suitable for fluorescence imaging of H2O2 in living tissues with deep penetration by using two-photon microscopy.
Co-reporter:Keyin Liu, Huiming Shang, Fangfang Meng, Yong Liu, Weiying Lin
Talanta 2016 Volume 147() pp:193-198
Publication Date(Web):15 January 2016
DOI:10.1016/j.talanta.2015.09.052
•We had constructed a novel photostable near-infrared fluorescent dye CSCN.•A reaction-based Cu2+ NIR probe CSCN–Cu based on CSCN was then designed.•CSCN–Cu owned a higher fluorescence enhancement than coordination-based probes.•CSCN–Cu can be used for imaging Cu2+ in living cells.Most of the near-infrared (NIR) fluorescent copper ion probes are coordination-based, and the fluorescence enhancement is between 10 and 20 folds. Herein, a novel NIR fluorescent dye named CSCN with excellent photostability and a reaction-based Cu2+ NIR probe named CSCN–Cu were reported. CSCN exhibited good photostability toward photo irradiation. CSCN–Cu showed lower background fluorescent interference and over 40-fold fluorescence enhancement in NIR region, it also exhibited good selectivity toward Cu2+ in Hepes solution. Biotic experiments demonstrated that CSCN–Cu possessed low toxicity and successfully imaged Cu2+ in living cells under the conditions performed.
Co-reporter:Jian-Yong Wang, Zhan-Rong Liu, Mingguang Ren, Beibei Deng, Weiying Lin
Journal of Photochemistry and Photobiology A: Chemistry 2016 Volume 317() pp:108-114
Publication Date(Web):15 February 2016
DOI:10.1016/j.jphotochem.2015.11.012
•A new two-photon fluorescent probe based on the GCTPOC two-photon fluorescent dye is designed and synthesized for detecting palladium(0) with fast response (6 min).•And ideal properties including good selectivity, high sensitivity and low cytotoxicity are depicted. A 130-fold fluorescence enhancement was obtained.•The new GCTPOC-Pd(0) probe could be employed to image Pd(0) in living cells and tissues with significant fluorescence emerging up to 170 μm by the way of two-photon fluorescence microscopy.A new two-photon fluorescent probe based on the GCTPOC two-photon fluorescent dye is designed and synthesized for detecting palladium(0) with fast response (6 min). And ideal properties including good selectivity, high sensitivity and low cytotoxicity are depicted. A 130-fold fluorescence enhancement was obtained. The new GCTPOC-Pd(0) probe could be employed to image Pd(0) in living cells and tissues with significant fluorescence emerging up to 170 μm by the way of two-photon fluorescence microscopy.A new two-photon fluorescent probe based on the GCTPOC two-photon fluorescent dye is designed and synthesized for detecting palladium(0) with fast response (6 min). And ideal properties including good selectivity, high sensitivity and low cytotoxicity are depicted. A 130-fold fluorescence enhancement was obtained. The new GCTPOC-Pd(0) probe could be employed to image Pd(0) in living cells and tissues with significant fluorescence emerging up to 170 μm by the way of two-photon fluorescence microscopy.
Co-reporter:Hua Chen, Yonghe Tang, Weiying Lin
TrAC Trends in Analytical Chemistry 2016 Volume 77() pp:242
Publication Date(Web):March 2016
DOI:10.1016/j.trac.2016.01.022
Co-reporter:Hua Chen, Yonghe Tang, Weiying Lin
TrAC Trends in Analytical Chemistry 2016 Volume 76() pp:166-181
Publication Date(Web):February 2016
DOI:10.1016/j.trac.2015.11.014
•The importance of fluorescent probes for specific detection of Cys/Hcy/GSH.•The underlying principles for the design of specific thiol fluorescent probes.•Structural design and the working principle of specific thiol fluorescent probes.•Representative examples of fluorescent probes which are capable of specific imaging of Cys/Hcy/GSH in living cells.Very recently, the development of fluorescent probes which are capable of specific imaging of Cys/Hcy/GSH in living cells has attracted great attention. The aim of this review is to highlight the representative examples of the specific thiol fluorescent probes reported from 2013 to 2014. However, in this review, we will restrict the discussion to specific thiol fluorescent probes developed based on organic fluorophores for bioimaging applications.
Co-reporter:Yonghe Tang, Dayoung Lee, Jiaoliang Wang, Guanhan Li, Jinghua Yu, Weiying Lin and Juyoung Yoon
Chemical Society Reviews 2015 vol. 44(Issue 15) pp:5003-5015
Publication Date(Web):14 May 2015
DOI:10.1039/C5CS00103J
Recently, the strategy of protection–deprotection of functional groups has been widely employed to design fluorescent probes, as the protection–deprotection of functional groups often induces a marked change in electronic properties. Significant advances have been made in the development of analyte-responsive fluorescent probes based on the protection–deprotection strategy. In this tutorial review, we highlight the representative examples of small-molecule based fluorescent probes for bioimaging, which are operated via the protection–deprotection of key functional groups such as aldehyde, hydroxyl, and amino functional groups reported from 2010 to 2014. The discussion includes the general protection–deprotection methods for aldehyde, hydroxyl, or amino groups, as well as the design strategies, sensing mechanisms, and deprotection modes of the representative fluorescent imaging probes applied to bio-imaging.
Co-reporter:Longwei He, Weiying Lin, Qiuyan Xu, Mingguang Ren, Haipeng Wei and Jian-Yong Wang
Chemical Science 2015 vol. 6(Issue 8) pp:4530-4536
Publication Date(Web):05 May 2015
DOI:10.1039/C5SC00348B
Heptamethine cyanines are favorable for fluorescence imaging applications in biological systems owing to their near-infrared (NIR) absorption and emission. However, it is very difficult to quench the fluorescence of NIR dyes by the classic photoinduced electron transfer mechanism due to their relatively high-lying occupied molecular orbital energy levels. Herein, we present a simple and effective “capping” approach to readily tune the fluorescence of NIR cyanines. The resulting new functional NIR CyBX (X = O, N, or S) dyes not only retain the intact tricarbocyanine scaffold, but also have a built-in switch to regulate the fluorescence by spiro-cyclization. When compared to traditional cyanines, novel CyBX dyes have a superior character in that their NIR optical properties can be readily tuned by the intrinsic spiro-cyclization mechanism. We expect that this “capping” strategy can be extended across not only the visual spectrum but also to structurally distinct fluorophores.
Co-reporter:Mingguang Ren, Beibei Deng, Jian-Yong Wang, Zhan-Rong Liu and Weiying Lin
Journal of Materials Chemistry A 2015 vol. 3(Issue 33) pp:6746-6752
Publication Date(Web):16 Jul 2015
DOI:10.1039/C5TB01184A
We have developed the first example of a fluorescence-enhanced and lysosome-targeted Cu2+ probe (Lys-Cu) with unique dual-channel emissions. The newly synthesized fluorescent probe Lys-Cu, which contains two recognition sites with different sensing mechanisms for Cu2+, displays fluorescence-enhanced dual-channel emissions with fluorescence response to Cu2+ in the lysosome pH environment. Fluorescence imaging shows that Lys-Cu is membrane-permeable and suitable for visualization of Cu2+ in lysosomes of living cells by dual-channel imaging.
Co-reporter:Kaibo Zheng, Weiying Lin, Weimin Huang, Xiaoyu Guan, Dan Cheng and Jian-Yong Wang
Journal of Materials Chemistry A 2015 vol. 3(Issue 5) pp:871-877
Publication Date(Web):14 Nov 2014
DOI:10.1039/C4TB01592D
An innovative class of aminochromene–aniliniumion conjugated far-red to near-infrared dyes, namely ACA, was developed. The design method for ACA dyes is straightforward and the synthesis of the ACA dyes is rapid and convenient. The ACA dyes display absorption and emission in the far-red to near-infrared region, good photostability and chemical stability. The ACA dyes could be used for bio-imaging not only in living cells but also in living animals. The design method described herein may be applicable to other types of long wavelength dyes and the ACA dyes may find interesting applications as sensing and labelling agents in diverse fields.
Co-reporter:Hua Chen, Weiying Lin, Wenqing Jiang, Baoli Dong, Haijun Cui and Yonghe Tang
Chemical Communications 2015 vol. 51(Issue 32) pp:6968-6971
Publication Date(Web):16 Mar 2015
DOI:10.1039/C5CC01242B
A new class of locked-flavylium fluorophores with tunable emission wavelengths based on intramolecular charge transfer were designed, synthesized, and evaluated. The optical studies indicate that sensor LF3 can display an intriguing character, fluorescence ratiometric response in three channels by tuning the ICT efficiencies.
Co-reporter:Kaibo Zheng, Weiying Lin, Dan Cheng, Hua Chen, Yong Liu and Keyin Liu
Chemical Communications 2015 vol. 51(Issue 26) pp:5754-5757
Publication Date(Web):19 Feb 2015
DOI:10.1039/C4CC10382C
The first two-photon fluorescent probe for specific detection of nitroxyl is designed and synthesized, and we have further demonstrated that the new two-photon fluorescent probe could be employed to image nitroxyl in living cells and tissues.
Co-reporter:Longwei He, Weiying Lin, Qiuyan Xu and Haipeng Wei
Chemical Communications 2015 vol. 51(Issue 8) pp:1510-1513
Publication Date(Web):02 Dec 2014
DOI:10.1039/C4CC08522A
We introduce a new FRET strategy to construct a ratiometric fluorescent H2S sensor. The ratio emission signal of the coumarin–naphthalimide dyad is modulated by the FRET process, which works in coordination with the ICT mechanism. The FRET process on/off is controlled through tuning the overlap level of the donor emission spectrum with the acceptor absorption via modulation of the acceptor fluorophore absorption wavelength. CN-N3 was applied to visualize both the intracellular exogenous and endogenous H2S through blue and green emission channels.
Co-reporter:Longwei He, Qiuyan Xu, Yong Liu, Haipeng Wei, Yonghe Tang, and Weiying Lin
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 23) pp:12809
Publication Date(Web):May 28, 2015
DOI:10.1021/acsami.5b01934
We have prepared a turn-on fluorescent probe for biothiols based on bromoketo coumarin (KC-Br). The emission intensity of the coumarin chromophore is modulated by both the heavy atom effect and internal charge transfer (ICT) process. The probe KC-Br is intrinsically nonfluorescent; however, after being reacted with thiols, the bromide moiety is substituted by the −SH group, which elicits a significant fluorescence increase. We surmised the free −NH2 group would further react with carbonyl in the Cys/Hcy-substituted intermediate product yielding to Schiff base compound KC-Cys/KC-Hcy, but not in compound KC-GSH. The ICT effect has a stronger influence in compound KC-GSH than that in compound KC-Cys/KC-Hcy, resulting in compound KC-GSH having a stronger fluorescence. Thus, the probe has a good selectivity for GSH over other various biologically relevant species and even two other similar biothiols (Cys/Hcy) and could image glutathione (GSH) in living cells. We expect the design concept presented in this work would be widely used for the design of fluorescent probes for distinguishing among biothiols.Keywords: bromoketo coumarin; fluorescence imaging; fluorescent probe; glutathione; specific detection;
Co-reporter:Kaibo Zheng, Weiying Lin, Li Tan, Dan Cheng
Analytica Chimica Acta 2015 Volume 853() pp:548-554
Publication Date(Web):1 January 2015
DOI:10.1016/j.aca.2014.10.024
•A two-photon fluorescent probe for sensing H2S was developed.•The probe shows a large turn on signal (120-fold enhancement).•The probe is suitable for fluorescence imaging of H2S in living cells and tissues.•The probe was capable of detecting H2S up to 170 μm depth in live tissues.A two-photon fluorescence turn-on H2S probe GCTPOC–H2S based on a two-photon platform with a large cross-section, GCTPOC, and a sensitive H2S recognition site, dinitrophenyl ether was constructed. The probe GCTPOC–H2S exhibits desirable properties such as high sensitivity, high selectivity, functioning well at physiological pH and low cytotoxicity. In particular, the probe shows a 120-fold enhancement in the presence of Na2S (500 μM), which is larger than the reported two-photon fluorescent H2S probes. The large fluorescence enhancement of the two-photon probe GCTPOC–H2S renders it attractive for imaging H2S in living tissues with deep tissue penetration. Significantly, we have demonstrated that the probe GCTPOC–H2S is suitable for fluorescence imaging of H2S in living tissues with deep penetration by using two-photon microscopy. The further application of the two-photon probe for the investigation of biological functions and pathological roles of H2S in living systems is under progress.
Co-reporter:Wenqing Jiang, Hua Chen, Yue Pan and Weiying Lin
Analytical Methods 2015 vol. 7(Issue 10) pp:4168-4172
Publication Date(Web):13 Apr 2015
DOI:10.1039/C5AY00737B
We have designed and synthesized the compound FR-thiol based on a new far-red platform as a turn-on fluorescent probe for biological thiols. The turn-on probe FR-thiol displayed a high selectivity and sensitivity to thiols. Finally, we have demonstrated that FR-thiol is suitable for video observation of biological thiols in living cells.
Co-reporter:Hua Chen; Weiying Lin;Haijun Cui;Wenqing Jiang
Chemistry - A European Journal 2015 Volume 21( Issue 2) pp:733-745
Publication Date(Web):
DOI:10.1002/chem.201404718
Abstract
The development of near-infrared (NIR) functional fluorescent dyes has gained increasing attention over the last few decades. Herein, we describe the development of a unique type of xanthene–cyanine fused NIR fluorophores, XC dyes, formed by reacting chloro-substituted cyanine with resorcin or its analogues under anhydrous conditions. XC dyes are a hybrid of cyanine and xanthene. The preliminary mechanistic studies indicate that the formation of XC compounds likely includes a sequence of cyclization and oxidation. XC dyes have absorption and emission in the NIR region, and their fluorescence properties can be controlled by modifications of the key hydroxyl and amine groups. The novel XC NIR dyes are advantageous over previously developed merocyanine dyes NIR dyes in their chemical stability against strong nucleophiles. Quantum chemical calculations reveal that the distinct properties of XC and HD dyes can be attributed to their structural differences. By taking advantage of the superior properties of XC dyes, we have further constructed a new NIR fluorescent probe, XC-H2S, which is capable of monitoring both the concentration- and time-dependent variations of H2S in living animals, highlighting the value of XC NIR dyes. We expect that the unique XC NIR dyes developed herein will find broader applications than HD NIR dyes as fluorescent platforms for the development of a wide variety of NIR fluorescent probes, in particular, those suitable for targets of interest that have strong nucleophilic character.
Co-reporter:Hua Chen;Baoli Dong;Yonghe Tang; Weiying Lin
Chemistry - A European Journal 2015 Volume 21( Issue 33) pp:11696-11700
Publication Date(Web):
DOI:10.1002/chem.201502226
Abstract
As selenocysteine (Sec) carries out the majority of the functions of the various Se-containing species in vivo, it is of high importance to develop reliable and rapid assays with biocompatibility to detect Sec. Herein, an NIR fluorescent turn-on probe for highly selective detection of selenol was designed and synthesized. The probe exhibits large turn-on signal upon treatment with selenocysteine (R-SeH), and it was further demonstrated that the new NIR fluorescent probe can be employed to image selenol in living animals.
Co-reporter:Longwei He;Sasa Zhu;Dr. Yong Liu;Yinan Xie;Qiuyan Xu;Haipeng Wei; Weiying Lin
Chemistry - A European Journal 2015 Volume 21( Issue 34) pp:12181-12187
Publication Date(Web):
DOI:10.1002/chem.201501375
Abstract
Broadband capturing and FRET-based light-harvesting molecular triads, CRBs, based on the coumarin–rhodamine–BODIPY platform were rationally designed and synthesized. The absorption band of CRBs starts from blue–green to yellow–orange regions (330–610 nm), covering the strong radiation scope of sunlight. The peripheral coumarin and BODIPY chromophore energy could transfer to the central acceptor rhodamine by a one-step direct way. The energy of the coumarin moiety could also transfer to the BODIPY unit, subsequently transferring to the rhodamine core by two-step sequential ways. Both the efficiencies of the coumarin moiety and the BODIPY unit to the rhodamine core in CRBs, determined by two different ways, are very high.
Co-reporter:Kaibo Zheng, Weiying Lin, Li Tan, Hua Chen and Haijun Cui
Chemical Science 2014 vol. 5(Issue 9) pp:3439-3448
Publication Date(Web):08 May 2014
DOI:10.1039/C4SC00283K
Two-photon fluorescent probes are favorable as powerful molecular tools for studies in biology and medicine. To construct two-photon fluorescent probes, it is necessary to have suitable two-photon fluorescent platforms. Herein, we present the rational design, synthesis, and spectral properties of carbazole–coumarin (CC) derivatives, a unique family of two-photon fluorescent dyes. Significantly, the action cross-sections of CC are tunable by modifications at the 4′-position of the coumarin moiety, implying that CC could be exploited as a novel platform to design two-photon fluorescent probes. Carbon monoxide (CO) plays an important role in many physiological and pathological processes. Although the tracking of CO in living cells has been previously reported, the detection of CO in much thicker biosamples, for instance, living tissues, has not been realized. It is known that two-photon fluorescent probes are favorable for monitoring biomolecules in living tissues. Thus, based on the unique CC platform, we rationally engineered CC–CO as the first two-photon fluorescent CO probe, and we further demonstrated that CC–CO could monitor the changes of CO levels not only in living cells but also in living tissues for the first time, demonstrating the value of our two-photon fluorescent CO probe. The CC platform is complementary to the current two-photon fluorescent platforms and it may be used to develop a wide variety of two-photon fluorescent probes. In addition, we expect that CC–CO and its next generation analogues may be useful for unraveling the functions of CO in complicated living systems.
Co-reporter:Longwei He, Weiying Lin, Qiuyan Xu, and Haipeng Wei
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 24) pp:22326
Publication Date(Web):November 19, 2014
DOI:10.1021/am506322h
The development of new functional fluorescent dyes has attracted great attention. Herein we have described a novel strategy to design a unique type of cyanine dyes by attaching two indolium moieties at the α-positions of the pyrrole core. The new type of cyanine dyes is named as PyCy fluorophores. Importantly, PyCy dyes can exhibit an exceptional feature, fluorescence turn-on response at pH varying from acidic to near-neutral conditions, and a ratiometric fluorescence response at pH varying from near-neutral to basic conditions. By taking advantage of the fluorescence turn-on response of PyCy2 at pH varying from acidic to near-neutral conditions and emission properties of PyCy2, we have demonstrated that a small-molecule fluorescent probe can image pH variations in living cells. Furthermore, we have demonstrated that PyCy2 can sense real-time pH changes under alkaline conditions induced by enzymes based on the ratiometric fluorescence response of PyCy2 at pH varying from near-neutral to basic conditions. We expect that the new design strategy for PyCy fluorophores may prompt the development of a wide variety of cyanine derivatives with desirable properties.Keywords: cyanine dyes; fluorescence imaging; pH probe; pyrrole; ratiometric; turn-on
Co-reporter:Li Tan, Weiying Lin, Sasa Zhu, Lin Yuan and Kaibo Zheng
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 26) pp:4637-4643
Publication Date(Web):02 May 2014
DOI:10.1039/C4OB00132J
Based on a novel coumarin-quinolinium platform, probe 2 was rationally designed and synthesized as a novel ratiometric fluorescent sensor for sulfite anions. The probe exhibited a wide dynamic concentration range for sulfite anions in a PBS buffer (containing 1 mg mL−1 BSA). More importantly, the probe was suitable for ratiometric fluorescence imaging in living cells with high sensitivity, favorable selectivity, and minimal cytotoxicity.
Co-reporter:Xiaoyu Guan, Weiying Lin and Weimin Huang
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 23) pp:3944-3949
Publication Date(Web):18 Mar 2014
DOI:10.1039/C4OB00131A
We have constructed a new rhodamine-based FRET platform, which was then used to develop a ratiometric fluorescent Cu2+ probe. The novel Cu2+ probe exhibits several favorable features including a large variation in the emission ratio, well-resolved emission peaks, high sensitivity, and high selectivity. Importantly, it is suitable for fluorescence imaging in living cells.
Co-reporter:Keyin Liu, Huiming Shang, Xiuqi Kong, Mingguang Ren, Jian-Yong Wang, Yong Liu, Weiying Lin
Biomaterials (September 2016) Volume 100() pp:
Publication Date(Web):September 2016
DOI:10.1016/j.biomaterials.2016.05.029
H2O2 as one of the most important ROS (Reactive Oxygen Species) has more attack activity to biomolecules such as DNA, RNA, protein and enzyme in alkaline environment and leads to a series of disease. However, no attention has been paid to the fluorescent detection of H2O2 in alkaline environment in the past. Herein, we reported the first ratiometric near-infrared fluorescent probe based on a boric acid derivative of Changsha near-infrared dye (CSBOH) for H2O2 detection in alkaline condition and the application for H2O2 imaging in vivo. ICT (intra-molecular charge transfer) mechanism was used in CSBOH to modulate the fluorescence change. The photophysical change of CSBOH was investigated by comparison with a phenol derivative of Changsha near-infrared dye (CSOH), a structural analogue bearing phenol group. In the presence of H2O2, CSBOH exhibited remarkably different fluorescence change at 650 nm and 720 nm when excited by 560 nm and 670 nm light respectively in alkaline buffer and showed high selectivity toward H2O2. Cellular experiments demonstrate that CSBOH can image endogenously generated H2O2 in macrophages and A431 cells. In vivo experiment demonstrates that both CSOH and CSBOH can be used for bio-imaging, and CSBOH can image H2O2 in living animal successfully.
Co-reporter:Zhan-Rong Liu, Yonghe Tang, An Xu, Weiying Lin
Biosensors and Bioelectronics (15 March 2017) Volume 89(Part 2) pp:853-858
Publication Date(Web):15 March 2017
DOI:10.1016/j.bios.2016.09.107
Co-reporter:Baoli Dong, Xuezhen Song, Xiuqi Kong, Chao Wang, Nan Zhang and Weiying Lin
Journal of Materials Chemistry A 2017 - vol. 5(Issue 5) pp:NaN995-995
Publication Date(Web):2016/12/28
DOI:10.1039/C6TB02957D
Lysosomal pH is closely related to the metastasis and apoptosis of cancer cells. Detecting lysosomal pH changes in cancer cells could be helpful for analyzing tumor progressions and in-depth study of the roles of lysosomes in tumor invasion and metastasis. Herein, we describe a novel tumor-targeting and lysosome-specific two-photon fluorescent probe (BN-lys) for imaging pH changes for the first time. Biotin was employed as the tumor-targeting module, and morpholine was selected as the lysosome-specific group and the pH site to control the fluorescence by photoinduced electron transfer (PET) mechanism. With a pKa value of 5.36, BN-lys showed a fast and reversible fluorescence response to pH. Under the guidance of the biotin group, BN-lys displayed strong one-photon and two-photon fluorescence responses to lysosomal pH in cancer cells, while it displayed weak fluorescence in normal cells. Furthermore, BN-lys could be applied for the imaging of chloroquine-stimulated lysosomal pH changes in living cells. These features demonstrate that this probe could have practical applications in biological research.
Co-reporter:Jian-Yong Wang, Zhan-Rong Liu, Mingguang Ren, Xiuqi Kong and Weiying Lin
Journal of Materials Chemistry A 2017 - vol. 5(Issue 1) pp:NaN138-138
Publication Date(Web):2016/11/15
DOI:10.1039/C6TB02610A
Cysteine (Cys), a small-molecule aminothiol, plays important roles in various physiological processes in connection with various diseases, such as skin lesions, edema, hair depigmentation and liver damage. We developed a novel two-photon fluorescent probe for sensing Cys in presence of GSH and Hcy in vivo. The two-photon fluorescent probe exhibited favorable properties, including fast response (about 20 min), good selectivity, and low cytotoxicity. Furthermore, it was successfully applied for imaging Cys in living cells and tissues.
Co-reporter:Hua Chen, Yonghe Tang, Huiming Shang, Xiuqi Kong, Rui Guo and Weiying Lin
Journal of Materials Chemistry A 2017 - vol. 5(Issue 13) pp:NaN2444-2444
Publication Date(Web):2017/02/27
DOI:10.1039/C7TB00174F
Full-color fluorescence imaging, which utilizes multiple fluorescent imaging agents with emission covering the whole visible spectrum in the same specimen, is a powerful approach to study molecular processes in living systems. To achieve two-photon full-color bioimaging, two-photon full-color-tunable fluorescent materials (with emission from the blue to near-infrared region) are highly desirable. Herein, in this work, we outline the rational design, synthesis, optical property studies, and biological imaging studies of a unique family of two-photon full-color-tunable functional fluorescent materials. Based on the proposed “hybridization” strategy, we judiciously engineered the first family of two-photon full-color-tunable functional fluorescent materials (TPFC) and their lysosome-targetable derivatives (TPFC-Lyso). The novel TPFC dyes display two-photon full-color-tunable fluorescence emission from the blue to near-infrared region in solutions. By exploiting their unprecedented two-photon full-color-tunable properties, the new TPFC dyes were successfully applied for two-photon full-color imaging in living cells, and in particular, in living tissues at different penetration depths for the first time. In addition, as representative cases, we have described the first report of two-photon full-color fluorescence imaging in subcellular organelles, lysosomes, using the novel lysosome-targetable TPFC-Lyso dyes.
Co-reporter:Longwei He, Xueling Yang, Yong Liu, Xiuqi Kong and Weiying Lin
Chemical Communications 2016 - vol. 52(Issue 21) pp:NaN4032-4032
Publication Date(Web):2016/02/08
DOI:10.1039/C5CC09796G
We have described a ratiometric fluorescent formaldehyde probe (RFFP) based on the 6-hydroxy naphthalene chromophore for the first time. The probe is suitable for ratiometric detection of formaldehyde both in the solution and living biological samples with two distinct emission bands.
Co-reporter:Yong Liu, Fangfang Meng, Longwei He, Keyin Liu and Weiying Lin
Chemical Communications 2016 - vol. 52(Issue 43) pp:NaN7019-7019
Publication Date(Web):2016/04/29
DOI:10.1039/C6CC02368A
Herein, we have developed a novel dual-site two-photon fluorescent probe TP-PMVC as the first paradigm of the probes, which can concurrently report lysosomes and lysosomal H2S with two different sets of fluorescence signals in the living cells and tissues.
Co-reporter:Kaibo Zheng, Weiying Lin, Dan Cheng, Hua Chen, Yong Liu and Keyin Liu
Chemical Communications 2015 - vol. 51(Issue 26) pp:NaN5757-5757
Publication Date(Web):2015/02/19
DOI:10.1039/C4CC10382C
The first two-photon fluorescent probe for specific detection of nitroxyl is designed and synthesized, and we have further demonstrated that the new two-photon fluorescent probe could be employed to image nitroxyl in living cells and tissues.
Co-reporter:Hua Chen, Weiying Lin, Wenqing Jiang, Baoli Dong, Haijun Cui and Yonghe Tang
Chemical Communications 2015 - vol. 51(Issue 32) pp:NaN6971-6971
Publication Date(Web):2015/03/16
DOI:10.1039/C5CC01242B
A new class of locked-flavylium fluorophores with tunable emission wavelengths based on intramolecular charge transfer were designed, synthesized, and evaluated. The optical studies indicate that sensor LF3 can display an intriguing character, fluorescence ratiometric response in three channels by tuning the ICT efficiencies.
Co-reporter:Mingguang Ren, Beibei Deng, Jian-Yong Wang, Zhan-Rong Liu and Weiying Lin
Journal of Materials Chemistry A 2015 - vol. 3(Issue 33) pp:NaN6752-6752
Publication Date(Web):2015/07/16
DOI:10.1039/C5TB01184A
We have developed the first example of a fluorescence-enhanced and lysosome-targeted Cu2+ probe (Lys-Cu) with unique dual-channel emissions. The newly synthesized fluorescent probe Lys-Cu, which contains two recognition sites with different sensing mechanisms for Cu2+, displays fluorescence-enhanced dual-channel emissions with fluorescence response to Cu2+ in the lysosome pH environment. Fluorescence imaging shows that Lys-Cu is membrane-permeable and suitable for visualization of Cu2+ in lysosomes of living cells by dual-channel imaging.
Co-reporter:Longwei He, Baoli Dong, Yong Liu and Weiying Lin
Chemical Society Reviews 2016 - vol. 45(Issue 23) pp:NaN6461-6461
Publication Date(Web):2016/09/26
DOI:10.1039/C6CS00413J
Fluorescence imaging is a powerful approach for noninvasive and real-time visualization and tracking of biomolecules and biological processes in living systems. The fluorescent chemosensors with dual/triple interplaying sensing mechanisms tend to provide diverse fluorescence signals or amplify the response signals, which are propitious to simultaneously track multiple analytes or to improve the selectivity and sensitivity of the chemosensors. Thus, the development of dual/triple sensing mechanism-based chemosensors has attracted great interest recently. This review highlights the representative cases of the fluorescent chemosensors with dual/triple interplaying sensing mechanisms published since 2010, and these chemosensors are classified according to the types of the interplaying sensing mechanisms, including ICT–FRET, PET–FRET, PET–ICT–ESIPT, etc.
Co-reporter:Yun Hak Lee, Yonghe Tang, Peter Verwilst, Weiying Lin and Jong Seung Kim
Chemical Communications 2016 - vol. 52(Issue 75) pp:NaN11250-11250
Publication Date(Web):2016/08/17
DOI:10.1039/C6CC06158C
A biotin appended formaldehyde sensor was found to specifically visualise both exogenous and endogenous levels of formaldehyde in biotin receptor positive cells over biotin negative cells by means of one- and two-photon excitation. The probe furthermore visualised endogenous levels of formaldehyde in tumour tissue slices up to 70 μm depth.
Co-reporter:Longwei He, Xueling Yang, Kaixin Xu and Weiying Lin
Chemical Communications 2017 - vol. 53(Issue 29) pp:NaN4083-4083
Publication Date(Web):2017/03/20
DOI:10.1039/C7CC00512A
The mitochondria-targeted turn-on fluorescent probe (Mito-FMP) based on a benzoxadiazole platform was developed for detection of malondialdehyde (MDA). Mito-FMP performed with large enhancement of the optical signal (774-fold) in response to MDA in an aqueous system and has the capability of monitoring endogenous MDA in HeLa cells and onion tissues.
Co-reporter:Baoli Dong, Xuezhen Song, Xiuqi Kong, Chao Wang, Nan Zhang and Weiying Lin
Journal of Materials Chemistry A 2017 - vol. 5(Issue 26) pp:NaN5224-5224
Publication Date(Web):2017/06/06
DOI:10.1039/C7TB00703E
Nitroxyl (HNO) plays important roles in the regulation of many physiological and pathological processes, and can serve as a potential therapeutic agent for cardiovascular disease. The development of HNO detection in living systems is greatly important for in-depth studies of its biosynthesis and activities. Herein, we describe a novel two-photon red-emissive fluorescence probe (RP) for imaging HNO in living cells and tissues. RP was based on a red-emissive dye, Rho, and showed no fluorescence. When responding to HNO, RP can emit red fluorescence with the emission wavelength at 638 nm. RP exhibited a sensitive and selective response to HNO. Theoretical calculations demonstrated that the overlaps between the HOMO and LUMO were large for Rho and tiny for RP, consistent with the absorption and fluorescence properties of Rho and RP. Assisted by three-dimensional (3D) imaging, the two-photon imaging of HNO with red emission color in living tissues was successfully performed.
Co-reporter:Yong Liu, Fangfang Meng, Jing Nie, Jie Niu, Xiaoqiang Yu and Weiying Lin
Journal of Materials Chemistry A 2017 - vol. 5(Issue 24) pp:NaN4731-4731
Publication Date(Web):2017/05/09
DOI:10.1039/C7TB00979H
The cell membranal liquid-ordered (Lo) phase can control the structure and function of cell membranes. In this study, we have engineered a novel two-photon (TP) fluorescent probe, TP-HVC18, which remarkably displayed two different fluorescence emission profiles in the aggregate and solution states in distinct polar environments. In accordance with its aggregate fluorescence, TP-HVC18 also can emit a red fluorescence signal in Lo phase vesicles. Taking advantage of this unique feature, we have demonstrated that the new TP probe TP-HVC18 is suitable for imaging membranal Lo phase by an aggregate fluorescence method. Furthermore, the robust probe also exhibited uncontinuous red fluorescence distribution in the cell membranal Lo phase. Based on this intriguing character, we also successfully showed that the novel probe can be employed to exhibit uncontinuous distribution of cell membranal Lo phase by a 3D imaging technique. We expect that this aggregation-based fluorescent platform may be extended for the development of a wide variety of TP fluorescent probes for detecting several biological species.
Co-reporter:Keyin Liu, Huiming Shang, Xiuqi Kong and Weiying Lin
Journal of Materials Chemistry A 2017 - vol. 5(Issue 21) pp:NaN3841-3841
Publication Date(Web):2017/04/17
DOI:10.1039/C7TB00187H
Biothiols such as cysteine (Cys) and glutathione (GSH) are important reductive species that are widely spread in the liver, heart, brain and so on, and are essential for maintaining the fundamental roles of these organs. Fluorescence detection of biothiols in living organisms is of great importance for exploring the metabolic pathways and physiological function in living organisms. Most of the near-infrared probes for biothiols have small Stokes shifts, usually less than 50 nm, which greatly hamper their applications in biological imaging; herein, a novel fluorescent CS-thiol probe based on a Changsha (CS) near-infrared dye analogue with a large Stokes shift was developed and applied for live animal imaging. In the presence of biothiols, such as Cys, CS-thiols show a broad fluorescence emission at 660 nm and exhibit high selectivity toward biothiols among other amino acids and reactive species. CS-Thiols exhibited little toxicity to HeLa cells and were successfully applied to image biothiols in living cells and living animals.
Co-reporter:Mingguang Ren, Beibei Deng, Kai Zhou, Jian-Yong Wang, Xiuqi Kong and Weiying Lin
Journal of Materials Chemistry A 2017 - vol. 5(Issue 10) pp:NaN1961-1961
Publication Date(Web):2017/02/07
DOI:10.1039/C6TB03388A
Nitroxyl plays crucial roles in many biological pathways and can serve as a potent therapeutic agent for the treatment of heart failure. Recent studies suggest that HNO may be produced in mitochondria and the HNO formed might have functional consequences for mitochondrial activity. However, in order to study the function of HNO in mitochondria, a suitable research method is needed. Herein, through rational design, we synthesized a new mitochondria-targeted fluorescent nitroxyl probe (Mito-HNO). The developed probe was highly selective toward HNO over other reactive nitrogen species and reducing species. In addition, the probe Mito-HNO was rapidly responsive and suitable for visualization of HNO in mitochondria in living cells. The probe is expected to be employed in further revealing the biological function of HNO in subcellular mitochondria.
Co-reporter:Xiaoyu Guan, Weiying Lin and Weimin Huang
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 23) pp:NaN3949-3949
Publication Date(Web):2014/03/18
DOI:10.1039/C4OB00131A
We have constructed a new rhodamine-based FRET platform, which was then used to develop a ratiometric fluorescent Cu2+ probe. The novel Cu2+ probe exhibits several favorable features including a large variation in the emission ratio, well-resolved emission peaks, high sensitivity, and high selectivity. Importantly, it is suitable for fluorescence imaging in living cells.
Co-reporter:Li Tan, Weiying Lin, Sasa Zhu, Lin Yuan and Kaibo Zheng
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 26) pp:NaN4643-4643
Publication Date(Web):2014/05/02
DOI:10.1039/C4OB00132J
Based on a novel coumarin-quinolinium platform, probe 2 was rationally designed and synthesized as a novel ratiometric fluorescent sensor for sulfite anions. The probe exhibited a wide dynamic concentration range for sulfite anions in a PBS buffer (containing 1 mg mL−1 BSA). More importantly, the probe was suitable for ratiometric fluorescence imaging in living cells with high sensitivity, favorable selectivity, and minimal cytotoxicity.
Co-reporter:Kaibo Zheng, Weiying Lin, Weimin Huang, Xiaoyu Guan, Dan Cheng and Jian-Yong Wang
Journal of Materials Chemistry A 2015 - vol. 3(Issue 5) pp:NaN877-877
Publication Date(Web):2014/11/14
DOI:10.1039/C4TB01592D
An innovative class of aminochromene–aniliniumion conjugated far-red to near-infrared dyes, namely ACA, was developed. The design method for ACA dyes is straightforward and the synthesis of the ACA dyes is rapid and convenient. The ACA dyes display absorption and emission in the far-red to near-infrared region, good photostability and chemical stability. The ACA dyes could be used for bio-imaging not only in living cells but also in living animals. The design method described herein may be applicable to other types of long wavelength dyes and the ACA dyes may find interesting applications as sensing and labelling agents in diverse fields.
Co-reporter:Mingguang Ren, Beibei Deng, Kai Zhou, Xiuqi Kong, Jian-Yong Wang, Gaoping Xu and Weiying Lin
Journal of Materials Chemistry A 2016 - vol. 4(Issue 27) pp:NaN4745-4745
Publication Date(Web):2016/06/13
DOI:10.1039/C6TB01085G
Hypochorous acid plays important roles in numerous physiological and pathological processes. At the cell organelle level, an abnormal concentration of hypochorous acid in the lysosomes causes redox imbalance and the loss of function of the lysosomes. Herein, the first small molecule based, lysosomal-targeted ratiometric fluorescent HOCl probe (Lyso-HA) was synthesized through a rational design. The new probe was highly selective toward HOCl over other reactive oxygen species and exhibits a large variation (up to 97-fold) in its fluorescence ratio (I585/I450), with good signal resolution. The probe Lyso-HA is membrane-permeable and is suitable for ratiometric visualization of exogenous and endogenous HOCl at lysosomes in living cells.
Co-reporter:Baoli Dong, Kaibo Zheng, Yonghe Tang and Weiying Lin
Journal of Materials Chemistry A 2016 - vol. 4(Issue 7) pp:NaN1269-1269
Publication Date(Web):2015/12/24
DOI:10.1039/C5TB02073E
Nitroxyl (HNO) is one of the important reactive nitrogen species (RNS) and show significant biological activities with significant therapeutic potential. Herein, three novel turn-on probes (NP-1–3) based on structurally related dyes with different emission colors as fluorescent scaffolds have been developed for detecting HNO in biological systems. The probes exhibit high sensitivity, excellent selectivity, desirable performance at physiological pH and low cytotoxicity. By incubating living cells with these probes simultaneously, we demonstrate the multicolor imaging of HNO with emission colors in the range of green to near-infrared (NIR) in living systems for the first time. Furthermore, probe NP-3 responds to HNO with a significant turn-on NIR fluorescence signal upon excitation in the NIR region, and it is successfully applied for sensing HNO in living mice.
Co-reporter:Yonghe Tang, Dayoung Lee, Jiaoliang Wang, Guanhan Li, Jinghua Yu, Weiying Lin and Juyoung Yoon
Chemical Society Reviews 2015 - vol. 44(Issue 15) pp:NaN5015-5015
Publication Date(Web):2015/05/14
DOI:10.1039/C5CS00103J
Recently, the strategy of protection–deprotection of functional groups has been widely employed to design fluorescent probes, as the protection–deprotection of functional groups often induces a marked change in electronic properties. Significant advances have been made in the development of analyte-responsive fluorescent probes based on the protection–deprotection strategy. In this tutorial review, we highlight the representative examples of small-molecule based fluorescent probes for bioimaging, which are operated via the protection–deprotection of key functional groups such as aldehyde, hydroxyl, and amino functional groups reported from 2010 to 2014. The discussion includes the general protection–deprotection methods for aldehyde, hydroxyl, or amino groups, as well as the design strategies, sensing mechanisms, and deprotection modes of the representative fluorescent imaging probes applied to bio-imaging.
Co-reporter:Kaibo Zheng, Weiying Lin, Li Tan, Hua Chen and Haijun Cui
Chemical Science (2010-Present) 2014 - vol. 5(Issue 9) pp:NaN3448-3448
Publication Date(Web):2014/05/08
DOI:10.1039/C4SC00283K
Two-photon fluorescent probes are favorable as powerful molecular tools for studies in biology and medicine. To construct two-photon fluorescent probes, it is necessary to have suitable two-photon fluorescent platforms. Herein, we present the rational design, synthesis, and spectral properties of carbazole–coumarin (CC) derivatives, a unique family of two-photon fluorescent dyes. Significantly, the action cross-sections of CC are tunable by modifications at the 4′-position of the coumarin moiety, implying that CC could be exploited as a novel platform to design two-photon fluorescent probes. Carbon monoxide (CO) plays an important role in many physiological and pathological processes. Although the tracking of CO in living cells has been previously reported, the detection of CO in much thicker biosamples, for instance, living tissues, has not been realized. It is known that two-photon fluorescent probes are favorable for monitoring biomolecules in living tissues. Thus, based on the unique CC platform, we rationally engineered CC–CO as the first two-photon fluorescent CO probe, and we further demonstrated that CC–CO could monitor the changes of CO levels not only in living cells but also in living tissues for the first time, demonstrating the value of our two-photon fluorescent CO probe. The CC platform is complementary to the current two-photon fluorescent platforms and it may be used to develop a wide variety of two-photon fluorescent probes. In addition, we expect that CC–CO and its next generation analogues may be useful for unraveling the functions of CO in complicated living systems.
Co-reporter:Hua Chen, Yonghe Tang, Mingguang Ren and Weiying Lin
Chemical Science (2010-Present) 2016 - vol. 7(Issue 3) pp:NaN1903-1903
Publication Date(Web):2015/11/24
DOI:10.1039/C5SC03591K
We describe a unique approach for the development of an interesting type of the fluorescent probes, which can show different modes of fluorescence signals to distinct concentration ranges of a target of interest. The key points for the design of the new type of the fluorescent probes include the judicious selection of the dye platforms and the corresponding high- and low-sensitivity sites. It is known that the normal concentrations of biological thiols have significant biological functions. However, up- or down-regulated concentrations of thiols may induce several diseases. Therefore, it is highly important to monitor the changes of thiol concentrations in living systems. Based on the proposed strategy, we engineer the novel NIR fluorescent probe, CHMC-thiol, which remarkably can display a turn-on signal to the low concentration range of thiols and a ratiometric response to the high concentration range of thiols for the first time. We anticipate that the intriguing strategy formulated herein will be widely useful for the development of concentration range-dependent fluorescent probes.
Co-reporter:Longwei He, Weiying Lin, Qiuyan Xu, Mingguang Ren, Haipeng Wei and Jian-Yong Wang
Chemical Science (2010-Present) 2015 - vol. 6(Issue 8) pp:NaN4536-4536
Publication Date(Web):2015/05/05
DOI:10.1039/C5SC00348B
Heptamethine cyanines are favorable for fluorescence imaging applications in biological systems owing to their near-infrared (NIR) absorption and emission. However, it is very difficult to quench the fluorescence of NIR dyes by the classic photoinduced electron transfer mechanism due to their relatively high-lying occupied molecular orbital energy levels. Herein, we present a simple and effective “capping” approach to readily tune the fluorescence of NIR cyanines. The resulting new functional NIR CyBX (X = O, N, or S) dyes not only retain the intact tricarbocyanine scaffold, but also have a built-in switch to regulate the fluorescence by spiro-cyclization. When compared to traditional cyanines, novel CyBX dyes have a superior character in that their NIR optical properties can be readily tuned by the intrinsic spiro-cyclization mechanism. We expect that this “capping” strategy can be extended across not only the visual spectrum but also to structurally distinct fluorophores.
Co-reporter:Longwei He, Xueling Yang, Mingguang Ren, Xiuqi Kong, Yong Liu and Weiying Lin
Chemical Communications 2016 - vol. 52(Issue 61) pp:NaN9585-9585
Publication Date(Web):2016/06/29
DOI:10.1039/C6CC04254F
An ultra-fast illuminating fluorescent formaldehyde (FA) probe (R6-FA) was designed and synthesized, and it exhibited a significant response to both FA in aqueous solution and as a gas. We have employed R6-FA not only to image FA in living cells, but also to detect FA in dried shiitake mushrooms and indoors for the first time, indicating its broad potential applications for monitoring FA in living systems, the food industry, and the environment.
Co-reporter:Yong Liu, Fangfang Meng, Longwei He, Xiaoqiang Yu and Weiying Lin
Chemical Communications 2016 - vol. 52(Issue 57) pp:NaN8841-8841
Publication Date(Web):2016/06/16
DOI:10.1039/C6CC03746A
It is found that 2,7-substituted carbazole derivative HVC-6 possesses distinct luminescence features in both aggregate and solution states. In view of this, probe HVC-6 realizes highly sensitive detection of RNA in pure water systems by an aggregation–disaggregation method for the first time.
Co-reporter:Mingguang Ren, Beibei Deng, Xiuqi Kong, Kai Zhou, Keyin Liu, Gaoping Xu and Weiying Lin
Chemical Communications 2016 - vol. 52(Issue 38) pp:NaN6418-6418
Publication Date(Web):2016/03/30
DOI:10.1039/C6CC00966B
By blocking the intramolecular twisted internal charge transfer (TICT) process, we designed and sythesized the first TICT-based fluorescent probe for hydrogen sulfide. The new probe exhibits high selectivity, good membrane-permeability and is suitable for visualization of exogenous and endogenous hydrogen sulfide in living cells.
Co-reporter:Longwei He, Weiying Lin, Qiuyan Xu and Haipeng Wei
Chemical Communications 2015 - vol. 51(Issue 8) pp:NaN1513-1513
Publication Date(Web):2014/12/02
DOI:10.1039/C4CC08522A
We introduce a new FRET strategy to construct a ratiometric fluorescent H2S sensor. The ratio emission signal of the coumarin–naphthalimide dyad is modulated by the FRET process, which works in coordination with the ICT mechanism. The FRET process on/off is controlled through tuning the overlap level of the donor emission spectrum with the acceptor absorption via modulation of the acceptor fluorophore absorption wavelength. CN-N3 was applied to visualize both the intracellular exogenous and endogenous H2S through blue and green emission channels.
