Co-reporter:Jing Zhang, Zhen Jin, Xiao-Xiao Hu, Hong-Min Meng, Jin Li, Xiao-Bing Zhang, Hong-Wen Liu, Tanggang Deng, Shan Yao, and Lili Feng
Analytical Chemistry August 1, 2017 Volume 89(Issue 15) pp:8097-8097
Publication Date(Web):July 4, 2017
DOI:10.1021/acs.analchem.7b01659
Drug-induced liver injury (DILI) is a potential complication of any prescribed medication. So far, the diagnosis of DILI is still a clinical challenge due to the lack of efficient diagnosis method. Glutathione S-transferase (GST), with a high concentration in liver cytosol, can reduce toxicity and facilitate urinary excretion by catalyzing the conjugation of glutathione (GSH) with reactive metabolites in liver. When liver is seriously damaged, GST and GSH will be released into plasma from liver cytosol, which caused a lower GST activity in liver cytosol. Therefore, monitoring the level of GST activity in liver tissue may be a potential strategy for diagnosis of DILI. Here, we reported a two-photon probe P-GST for GST activity detection for the first time. In the proposed design, a donor-π-acceptor (D-π-A) structured naphthalimide derivative with efficient two-photon properties was chosen as the fluorescent group, and a 2,4-dinitrobenzenesulfonate group was employed as the GST recognition unit, which also acted as the fluorescence quencher. In the present of GST and GSH, the recognition unit was removed and the fluorophore was released, causing a 40-fold enhancement of fluorescence signal with a detection limit of 35 ng/mL. At last, P-GST was successfully applied in two-photon imaging of GST in cells and DILI samples, which demonstrated its practical application in complex biosystems as a potential method for diagnosis of DILI.
Co-reporter:Li-Li Feng, Yong-Xiang Wu, Dai-Liang Zhang, Xiao-Xiao Hu, Jing Zhang, Peng Wang, Zhi-Ling Song, Xiao-Bing Zhang, and Weihong Tan
Analytical Chemistry April 4, 2017 Volume 89(Issue 7) pp:4077-4077
Publication Date(Web):March 10, 2017
DOI:10.1021/acs.analchem.6b04943
Ascorbic acid (AA), as one of the most important vitamins, participates in various physiological reactions in the human body and is implicated with many diseases. Therefore, the development of effective methods for monitoring the AA level in living systems is of great significance. Up to date, various technologies have been developed for the detection of AA. However, few methods can realize the direct detection of endogenous AA in living cells. In this work, we for the first time reported that near-infrared (NIR) graphene quantum dots (GQD) possessed good two-photon fluorescence properties with a NIR emission at 660 nm upon exciting with 810 nm femtosecond pulses and a two-photon (TP) excitation action cross-section (δΦ) of 25.12 GM. They were then employed to construct a TP nanoprobe for detection and bioimaging of endogenous AA in living cells. In this nanosystem, NIR GQDs (NGs), which exhibited lower fluorescence background in living system to afford improved fluorescence imaging resolution, were acted as fluorescence reporters. Also CoOOH nanoflakes were chosen as fluorescence quenchers by forming on the surface of NGs. Once AA was introduced, CoOOH was reduced to Co2+, which resulted in a “turn-on” fluorescence signal of NGs. The proposed nanoprobe demonstrated high sensitivity toward AA, with the observed LOD of 270 nM. It also showed high selectivity to AA with excellent photostability. Moreover, the nanoprobe was successfully used for TP imaging of endogenous AA in living cells as well as deep tissue imaging.
Co-reporter:Mengyi Xiong, Qiming Rong, Hong-min Meng, Xiao-bing Zhang
Biosensors and Bioelectronics 2017 Volume 89(Part 1) pp:212-223
Publication Date(Web):15 March 2017
DOI:10.1016/j.bios.2016.03.043
•Advance of two-dimensional graphitic carbon nitride nanosheets (CNNSs) was present.•The deep research on CNNSs offers valuable strategies for biosensing applications.•Properties of CNNSs and their applications in biosensing were discussed in detail.•Deficiencies and perspectives about the applications of CNNSs were summarized.Two-dimensional graphitic carbon nitride nanosheets (CNNSs) with planar graphene-like structure have stimulated increasingly research interest in recent years due to their unique physicochemical properties. CNNSs possess superior stability, high fluorescence quantum yield, low-toxicity, excellent biocompatibility, unique electroluminescent and photoelectrochemical properties, which make them appropriate candidates for biosensing. In this review, we first introduce the preparation and unique properties of CNNSs, with emphasis on their superior properties for biosensing. Then, recent advances of CNNSs in photoelectrochemical biosensing, electrochemiluminescence biosensing and fluorescence biosensing are highlighted. An additional attention is paid to the marriage of CNNSs and nucleic acids, which exhibits great potentials in both biosensing and intracellular imaging. Finally, current challenges and opportunities of this 2D material are outlined. Inspired by the unique properties of CNNSs and their advantages in biological applications, we expect that more attention will be drawn to this promising 2D material and extensive applications can be found in bioanalysis and diseases diagnosis.
Co-reporter:Danqing Lu, Liyi Zhou, Ruowen Wang, Xiao-Bing Zhang, Lei He, Jing Zhang, Xiaoxiao Hu, Weihong Tan
Sensors and Actuators B: Chemical 2017 Volume 250(Volume 250) pp:
Publication Date(Web):1 October 2017
DOI:10.1016/j.snb.2017.04.041
•A Two-photon fluorescent probe based on non-redox strategy for endogenous O2− detection has been successfully designed and synthesized for intracellular biosensing and bioimaging.•The probe displayed excellent in vitro analytical performance, as well as two-photon bioimaging of endogenous O2− in live cells and tissue slices.•By taking advantage of the reported two-photon fluorescent probe, further understanding of the roles of O2− in biological and pathological events is anticipated.Superoxide anion radical (O2−), the “primary” reactive oxygen species (ROS) in living systems, is linked to a variety of physiological and pathological processes. Therefore, developing an effective strategy to monitor the fluctuation of O2− in biological systems is of great importance. This paper describes a new turn-on two-photon fluorescent probe for endogenous O2− detection and imaging, which was rationally designed and synthesized via a non-redox strategy. In the presence of O2−, the probe exhibited notable fluorescence enhancement (∼235-fold) with a low detection limit down to 1 nM, indicating a high signal-to-background ratio and excellent sensitivity. In addition, short response time, good biocompatibility, low cytotoxicity, long-term stability against light illumination, specificity to O2− over general reductants, and pH stability were demonstrated, indicating that the requirements for cellular O2− determination are met. Furthermore, the probe was successfully applied in two-photon fluorescence imaging of endogenous O2− in living cells and tissues and showed high imaging resolution and a deep-tissue imaging depth of ∼150 μm, illustrating the promising potential for practical applications in complex biosystems and providing a valuable theoretical basis and technical support for the study of physiological and pathological functions of O2−.
Co-reporter:Peng Wang;Cheng Zhang;Hong-Wen Liu;Mengyi Xiong;Sheng-Yan Yin;Yue Yang;Xiao-Xiao Hu;Xia Yin;Weihong Tan
Chemical Science (2010-Present) 2017 vol. 8(Issue 12) pp:8214-8220
Publication Date(Web):2017/11/20
DOI:10.1039/C7SC03977H
Fluorescence quantitative analyses for vital biomolecules are in great demand in biomedical science owing to their unique detection advantages with rapid, sensitive, non-damaging and specific identification. However, available fluorescence strategies for quantitative detection are usually hard to design and achieve. Inspired by supramolecular chemistry, a two-photon-excited fluorescent supramolecular nanoplatform (TPSNP) was designed for quantitative analysis with three parts: host molecules (β-CD polymers), a guest fluorophore of sensing probes (Np–Ad) and a guest internal reference (NpRh–Ad). In this strategy, the TPSNP possesses the merits of (i) improved water-solubility and biocompatibility; (ii) increased tissue penetration depth for bioimaging by two-photon excitation; (iii) quantitative and tunable assembly of functional guest molecules to obtain optimized detection conditions; (iv) a common approach to avoid the limitation of complicated design by adjustment of sensing probes; and (v) accurate quantitative analysis by virtue of reference molecules. As a proof-of-concept, we utilized the two-photon fluorescent probe NHS–Ad-based TPSNP-1 to realize accurate quantitative analysis of hydrogen sulfide (H2S), with high sensitivity and good selectivity in live cells, deep tissues and ex vivo-dissected organs, suggesting that the TPSNP is an ideal quantitative indicator for clinical samples. What’s more, TPSNP will pave the way for designing and preparing advanced supramolecular sensors for biosensing and biomedicine.
Co-reporter:Peng Wang;Cheng Zhang;Hong-Wen Liu;Mengyi Xiong;Sheng-Yan Yin;Yue Yang;Xiao-Xiao Hu;Xia Yin;Weihong Tan
Chemical Science (2010-Present) 2017 vol. 8(Issue 12) pp:8214-8220
Publication Date(Web):2017/11/20
DOI:10.1039/C7SC03977H
Fluorescence quantitative analyses for vital biomolecules are in great demand in biomedical science owing to their unique detection advantages with rapid, sensitive, non-damaging and specific identification. However, available fluorescence strategies for quantitative detection are usually hard to design and achieve. Inspired by supramolecular chemistry, a two-photon-excited fluorescent supramolecular nanoplatform (TPSNP) was designed for quantitative analysis with three parts: host molecules (β-CD polymers), a guest fluorophore of sensing probes (Np–Ad) and a guest internal reference (NpRh–Ad). In this strategy, the TPSNP possesses the merits of (i) improved water-solubility and biocompatibility; (ii) increased tissue penetration depth for bioimaging by two-photon excitation; (iii) quantitative and tunable assembly of functional guest molecules to obtain optimized detection conditions; (iv) a common approach to avoid the limitation of complicated design by adjustment of sensing probes; and (v) accurate quantitative analysis by virtue of reference molecules. As a proof-of-concept, we utilized the two-photon fluorescent probe NHS–Ad-based TPSNP-1 to realize accurate quantitative analysis of hydrogen sulfide (H2S), with high sensitivity and good selectivity in live cells, deep tissues and ex vivo-dissected organs, suggesting that the TPSNP is an ideal quantitative indicator for clinical samples. What’s more, TPSNP will pave the way for designing and preparing advanced supramolecular sensors for biosensing and biomedicine.
Co-reporter:Peng Wang;Jing Zhang;Hong-Wen Liu;Xiao-Xiao Hu;Li-Li Feng;Xia Yin
Analyst (1876-Present) 2017 vol. 142(Issue 10) pp:1813-1820
Publication Date(Web):2017/05/15
DOI:10.1039/C7AN00229G
Oxidative stress, a disturbance in the balance between oxidant/antioxidant ratios, is associated with cancer, aging, inflammation, neurodegenerative diseases and other conditions. γ-Glutamyltranspeptidase (GGT) is a redox-related enzyme that plays a key role in mitigating the effects of oxidative stress by maintaining cellular glutathione (GSH) metabolism and homeostasis. Therefore, oxidative stress will upregulate the intracellular GGT level. To better understand the major pathophysiological resist mechanism to oxidative injury in mediating many disease states, we designed and synthesized a novel two-photon (TP) fluorescent turn-on probe, Np-Glu, for GGT detection and bioimaging. Under the optimized conditions, Np-Glu exhibited remarkable fluorescence enhancement (150-fold), good selectivity and high sensitivity (LOD is 0.033 U L−1), with a wide linear concentration range (0–50 U L−1). More importantly, the probe Np-Glu was successfully applied in one-photon and TP fluorescence imaging of GGT activity in an oxidative stress model in living cells and tissues, suggesting Np-Glu as an ideal indicator for clinical and biological samples.
Co-reporter:Xuan Yu;Liang Gong;Jing Zhang;Zilong Zhao;Xiaobing Zhang
Science China Chemistry 2017 Volume 60( Issue 10) pp:1318-1323
Publication Date(Web):11 August 2017
DOI:10.1007/s11426-017-9108-5
Chemotherapy-induced multi-drug resistance (MDR) in tumors poses a huge challenge for clinical treatment of tumors. The downregulation of the multi-drug resistance relative protein, represented by P-glycoprotein (P-gp), can reverse MDR of cancer cells. In this study, we developed doxorubicin-loading nanocarrier based on the assembly of protein and antisense oligonucleotide (ASO) to combat MDR of cancer cells. The data demonstrate that the nanocarrier can efficiently deliver ASO to cytoplasm and downregulate the P-glycoprotein expression, subsequently improving the therapeutic effects of Dox in doxorubicin-resistant MCF-7/ADR cancer cells. The preparation is simple and effective, providing a powerful tool for gene delivery. Therefore, our nanocarrier shows high promise in cancer treatment.
Co-reporter:Huanhuan Fan;Xiaobing Zhang;Yi Lu
Science China Chemistry 2017 Volume 60( Issue 5) pp:591-601
Publication Date(Web):13 March 2017
DOI:10.1007/s11426-016-0472-1
DNAzymes, generated through in vitro selection processes, are single-stranded DNA catalysts that can catalyze a wide variety of reactions, such as RNA or DNA cleavage and ligation or DNA phosphorylation. Based on specific cofactor dependence and potent catalytic ability, DNAzymes have been extensively used to develop highly sensitive and specific sensing platforms for metal ions, small molecules, and biomacromolecules. However, in spite of their multiple strong enzymatic turnover properties, few reports have addressed the potential application of RNA-cleaving DNAzymes as therapeutic gene-silencing agents. The main challenges are being met with low efficiency of cellular uptake, instability and the lack of sufficient cofactors for cellular or in vivo study, which have limited the development of DNAzymes for clinical application. In recent years, substantial progress has been made to enhance the delivery efficiency and stability of DNAzymes by developing variety of methods. Smart metal oxide nanomaterials have also been used to meet the requirement of cofactors in situ. This review focuses on the gene silencing application of DNAzymes as well as their physicochemical properties. Methods of increasing the efficacy of DNAzymes in gene therapy are also discussed: delivery systems to enhance the cellular uptake, modifications to enhance the stability and smart systems to generate sufficient cofactors in situ. Finally, some future trends and perspectives in these research areas are outlined.
Co-reporter:Dr. Hong-Wen Liu;Ke Li;Dr. Xiao-Xiao Hu;Longmin Zhu;Qiming Rong;Yongchao Liu; Dr. Xiao-Bing Zhang; Dr. Jens Hasserodt; Dr. Feng-Li Qu; Dr. Weihong Tan
Angewandte Chemie 2017 Volume 129(Issue 39) pp:11950-11954
Publication Date(Web):2017/09/18
DOI:10.1002/ange.201705747
AbstractCurrent enzyme-responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited-state intramolecular proton transfer (ESIPT)-based solid-state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme-responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion-resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer.
Co-reporter:Dr. Hong-Wen Liu;Ke Li;Dr. Xiao-Xiao Hu;Longmin Zhu;Qiming Rong;Yongchao Liu; Dr. Xiao-Bing Zhang; Dr. Jens Hasserodt; Dr. Feng-Li Qu; Dr. Weihong Tan
Angewandte Chemie International Edition 2017 Volume 56(Issue 39) pp:11788-11792
Publication Date(Web):2017/09/18
DOI:10.1002/anie.201705747
AbstractCurrent enzyme-responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited-state intramolecular proton transfer (ESIPT)-based solid-state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme-responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion-resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer.
Co-reporter:Hong-Wen Liu, Xiao-Xiao Hu, Longmin Zhu, Ke Li, Qiming Rong, Lin Yuan, Xiao-Bing Zhang, Weihong Tan
Talanta 2017 Volume 175(Volume 175) pp:
Publication Date(Web):1 December 2017
DOI:10.1016/j.talanta.2017.04.081
•ALP levels of expression have been routinely used for disease diagnosis.•A new near-infrared fluorescent probe has been developed for detection ALP activity.•The probe is successfully applied for imaging ALP activity in living tumor.Alkaline phosphatase (ALP), one of the important hydrolases, is associated with the progress of many diseases as a well-defined biomarker. Fluorescence imaging of ALP in living organisms is of great importance for biological studies. However, in vivo detection of ALP remains a great challenge because current fluorescent probes show short excitation and emission wavelength, which are not desired for in vivo fluorescence imaging. Herein we reported a near-infrared (NIR) fluorescent probe (NALP) for turn-on trapping of ALP activity in living cancer cells and tumors. NALP was composed of a NIR-emitting fluorophore as a reporter and phosphate as a triggered moiety. Phosphate group was directly tethered to the hydroxyl group of fluorophore, which prohibited the fluorescence. The probe exhibited a high selectivity and remarkable fluorescence turn-on response to ALP in aqueous solutions with a detection limit of 0.28 U/L. Benefiting from NIR excitation and emission, high contrast on the imaging signal could be achieved in response to endogenous ALP activity. Impressively, not only we successfully used NALP for imaging of endogenous ALP activity in cancer cells, but also, applied it for fluorescence imaging of ALP in tumor tissues and living tumor xenograft in nude mice for the first time. The probe was expected to be promising tool for practical application in disease diagnosis on the roles of ALP in disease.A promising near-infrared fluorescent probe for turn-on trapping of ALP activity in living cancer cells, tumor tissues and living tumor xenograft in nude mice was first proposed.Download high-res image (159KB)Download full-size image
Co-reporter:Hong-Wen Liu;Xiao-Xiao Hu;Ke Li;Yongchao Liu;Qiming Rong;Longmin Zhu;Lin Yuan;Feng-Li Qu;Weihong Tan
Chemical Science (2010-Present) 2017 vol. 8(Issue 11) pp:7689-7695
Publication Date(Web):2017/10/23
DOI:10.1039/C7SC03454G
Nontoxic prodrugs, especially activated by tumor microenvironment, are urgently required for reducing the side effects of cancer therapy. And combination of chemo-photodynamic therapy prodrugs show effectively synergetic therapeutic efficiency, however, this goal has not been achieved in a single molecule. In this work, we developed a mitochondrial-targeted prodrug PNPS for near infrared (NIR) fluorescence imaging guided and synergetic chemo-photodynamic precise cancer therapy for the first time. PNPS contains a NIR photosensitizer (NPS) and an anticancer drug 5′-deoxy-5-fluorouridine (5′-DFUR). These two parts are linked and caged through a bisboronate group, displaying no fluorescence and very low cytotoxicity. In the presence of H2O2, the bisboronate group is broken, resulting in activation of NPS for NIR photodynamic therapy and activation of 5′-DFUR for chemotherapy. The activated NPS can also provide a NIR fluorescence signal for monitoring the release of activated drug. Taking advantage of the high H2O2 concentration in cancer cells, PNPS exhibits higher cytotoxicity to cancer cells than normal cells, resulting in lower side effects. In addition, based on its mitochondrial-targeted ability, PNPS exhibits enhanced chemotherapy efficiency compare to free 5′-DFUR. It also demonstrated a remarkably improved and synergistic chemo-photodynamic therapeutic effect for cancer cells. Moreover, PNPS exhibits excellent tumor microenvironment-activated performance when intravenously injected into tumor-bearing nude mice, as demonstrated by in vivo fluorescence imaging. Thus, PNPS is a promising prodrug for cancer therapy based on its tumor microenvironment-activated drug release, synergistic therapeutic effect and “turn-on” NIR imaging guide.
Co-reporter:Hong-Min Meng, Hui Liu, Hailan Kuai, Ruizi Peng, Liuting Mo and Xiao-Bing Zhang
Chemical Society Reviews 2016 vol. 45(Issue 9) pp:2583-2602
Publication Date(Web):08 Mar 2016
DOI:10.1039/C5CS00645G
The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson–Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for in vivo applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field.
Co-reporter:Yi-Jun Gong, Xiao-Bing Zhang, Guo-Jiang Mao, Li Su, Hong-Min Meng, Weihong Tan, Suling Feng and Guisheng Zhang
Chemical Science 2016 vol. 7(Issue 3) pp:2275-2285
Publication Date(Web):04 Jan 2016
DOI:10.1039/C5SC04014K
Near-infrared (NIR) fluorescent probes are attractive molecular tools for bioimaging because of their low autofluorescence interference, deep tissue penetration, and minimal damage to sample. However, most previously reported NIR probes exhibit small Stokes shift, typically less than 30 nm, and low fluorescence quantum yield, strictly limited contrast and spatial resolution for bioimaging. Herein, by expanding the π-conjugated system of rhodamine B, while, at the same time, keeping its rigid and planar structure, we reported an efficient NIR dye, HN7, with large stokes shift of 73 nm and fluorescence quantum yield as high as 0.72 in ethanol, values superior to those of such traditional cyanine NIR dyes as Cy5. Using HN7, living cells, tissues and mice were imaged, and the results showed significantly enhanced contrast, improved spatial resolution, and satisfactory tissue imaging depth when compared to Cy5. Moreover, the nonfluorescent spirocyclic structure of rhodamine B is an inherent component of HN7; therefore, our strategy provided a universal platform for the design of efficient NIR turn-on bioimaging probes for various targets. As a proof-of-concept, two different NIR probes, HN7-N2 and HN7-S for NO and Hg2+, respectively, were designed, synthesized, and successfully applied for the imaging of NO and Hg2+ in living cells, tissues and mice, respectively, demonstrating the potential bioimaging applications of the new probes. In sum, this new type of dye may present new avenues for the development of efficient NIR fluorescent probes for contrast-enhanced imaging in biological applications.
Co-reporter:Xiaoyan Zhu, Mengyi Xiong, Hong-wen Liu, Guo-jiang Mao, Liyi Zhou, Jing Zhang, Xiaoxiao Hu, Xiao-Bing Zhang and Weihong Tan
Chemical Communications 2016 vol. 52(Issue 4) pp:733-736
Publication Date(Web):03 Nov 2015
DOI:10.1039/C5CC08695G
A FRET-based two-photon fluorescent probe, P-Np-Rhod, which exhibited a fast and high selective ratiometric response to nitroxyl, was first proposed. P-Np-Rhod was successfully applied to two-photon dual-channel imaging of nitroxyl in living cells and tissues with less cross-talk between channels and satisfactory deep-tissue imaging depth.
Co-reporter:Mengyi Xiong, Huijie Zhu, Qiming Rong, Chan Yang, Liping Qiu, Xiao-Bing Zhang and Weihong Tan
Chemical Communications 2016 vol. 52(Issue 25) pp:4679-4682
Publication Date(Web):01 Mar 2016
DOI:10.1039/C6CC00192K
Cell-surface fluorescent probes are effective tools in cell biology and engineering. Here, we for the first time report a diacyllipid–aptamer conjugate-based fluorescent probe which could anchor on cell membrane for real-time tracking of potassium ions in the cell microenvironment.
Co-reporter:Yifan Lv, Ruizi Peng, Yu Zhou, Xiaobing Zhang and Weihong Tan
Chemical Communications 2016 vol. 52(Issue 7) pp:1413-1415
Publication Date(Web):18 Nov 2015
DOI:10.1039/C5CC06937H
A catalytic self-assembled DNA dendritic complex was herein reported and used for siRNA-based gene silencing. This kind of one-pot DNA dendrimer can be conveniently prepared as needed, and it was demonstrated to have better silencing efficiency and lower cytotoxicity than commercial cationic lipid transfection agents.
Co-reporter:Hong-Min Meng, Xiao-Bing Zhang, Chan Yang, Hailan Kuai, Guo-Jiang Mao, Liang Gong, Wenhan Zhang, Suling Feng, and Junbiao Chang
Analytical Chemistry 2016 Volume 88(Issue 11) pp:6057
Publication Date(Web):May 10, 2016
DOI:10.1021/acs.analchem.6b01352
Ascorbic acid (AA) serves as a key coenzyme in many metabolic pathways, and its abnormal level is found to be associated with several diseases. Therefore, monitoring AA level in living systems is of great biomedical significance. In comparison with one-photon excited fluorescent probes, two-photon (TP) excited probes are more suitable for bioimaging, as they could afford higher imaging resolution with deeper imaging depth. Here, we report for the first time an efficient TP fluorescence probe for turn-on detection and imaging of AA in living cells and tissues. In this nanosystem, the negatively charged two-photon nanoparticles (TPNPs), which were prepared by modifying the silica nanoparticles with a two-photon dye, could adsorb cobalt oxyhydroxide (CoOOH) nanoflakes which carried positive charge by electrostatic force, leading to a remarkable decrease in their fluorescence intensity. However, the introduction of AA could induce the fluorescence recovery of the nanoprobe because it could reduce CoOOH into Co2+ and result in the destruction of the CoOOH nanoflakes. The nanosystem exhibits a high sensitivity toward AA, with a LOD of 170 nM observed. It also shows high selectivity toward AA over common potential interfering species. The nanoprobe possessed both the advantages of TP imaging and excellent membrane-permeability and good biocompatibility of the silica nanoparticles and was successfully applied in TP-excited imaging of AA in living cells and tissues.
Co-reporter:Liang Cui, Ruizi Peng, Ting Fu, Xiaobing Zhang, Cuichen Wu, Huapei Chen, Hao Liang, Chaoyong James Yang, and Weihong Tan
Analytical Chemistry 2016 Volume 88(Issue 3) pp:1850
Publication Date(Web):December 22, 2015
DOI:10.1021/acs.analchem.5b04170
DNAzymes, an important type of metal ion-dependent functional nucleic acid, are widely applied in bioanalysis and biomedicine. However, the use of DNAzymes in practical applications has been impeded by the intrinsic drawbacks of natural nucleic acids, such as interferences from nuclease digestion and protein binding, as well as undesired intermolecular interactions with other nucleic acids. On the basis of reciprocal chiral substrate specificity, the enantiomer of D-DNAzyme, L-DNAzyme, could initiate catalytic cleavage activity with the same achiral metal ion as a cofactor. Meanwhile, by using the advantage of nonbiological L-DNAzyme, which is not subject to the interferences of biological matrixes, as recognition units, a facile and stable L-DNAzyme sensor was proposed for sensing metal ions in complex biological samples and live cells.
Co-reporter:Yong-Xiang Wu, Xiao-Bing Zhang, Dai-Liang Zhang, Cui-Cui Zhang, Jun-Bin Li, Yuan Wu, Zhi-Ling Song, Ru-Qin Yu, and Weihong Tan
Analytical Chemistry 2016 Volume 88(Issue 3) pp:1639
Publication Date(Web):January 8, 2016
DOI:10.1021/acs.analchem.5b03573
Upconversion nanoparticles (UCNPs) possess several unique features, but they suffer from surface quenching effects caused by the interaction between the UCNPs and fluorophore. Thus, the use of UCNPs for target-induced emission changes for biosensing and bioimaging has been challenging. In this work, fluorophore and UCNPs are effectively separated by a silica transition layer with a thickness of about 4 nm to diminish the surface quenching effect of the UCNPs, allowing a universal and efficient luminescence resonance energy transfer (LRET) ratiometric upconversion luminescence nanoplatform for biosensing applications. A pH-sensitive fluorescein derivative and Hg2+-sensitive rhodamine B were chosen as fluoroionphores to construct the LRET nanoprobes. Both showed satisfactory target-triggered ratiometric upconversion luminescence responses in both solution and live cells, indicating that this strategy may find wide applications in the design of nanoprobes for various biorelated targets.
Co-reporter:Xiaoyan Zhu, Longming Zhu, Hong-wen Liu, Xiaoxiao Hu, Rui-zi Peng, Jing Zhang, Xiao-Bing Zhang, Weihong Tan
Analytica Chimica Acta 2016 Volume 937() pp:136-142
Publication Date(Web):21 September 2016
DOI:10.1016/j.aca.2016.07.017
•A FRET-based two-photon fluorescent probe for detecting SO2 derivatives was proposed.•The probe shows high sensitivity, excellent selectivity, rapid response as well as low cytotoxicity.•The probe was capable of detecting SO2 derivatives up to 170 μm depth in tissues.SO2 and its derivatives (bisulfite/sulfite) play crucial roles in several physiological processes. Therefore, development of reliable analytical methods for monitoring SO2 and its derivatives in biological systems is very significant. In this paper, a FRET-based two-photon fluorescent turn-on probe, A-HCy, was proposed for specific detection of SO2 derivatives through the bisulfite/sulfite-promoted Michael addition reaction. In this FRET system, an acedan (2-acetyl-6-dialkylaminonaphthalene) moiety was selected as a two-photon donor and a hemicyanine derivative served as both the quencher and the recognition unit for bisulfite/sulfite. A-HCy exhibited excellent selectivity and rapid response to HSO3− with a detection limit of 0.24 μM. More importantly, probe A-HCy was first successfully applied in two-photon fluorescence imaging of biological SO2 derivatives in living cells and tissues, suggesting its great potential for practical application in biological systems.
Co-reporter:Jun-Bin Li, Qian-Qian Wang, Lin Yuan, Yong-Xiang Wu, Xiao-Xiao Hu, Xiao-Bing Zhang and Weihong Tan
Analyst 2016 vol. 141(Issue 11) pp:3395-3402
Publication Date(Web):14 Apr 2016
DOI:10.1039/C6AN00473C
Formaldehyde (FA) plays an important role in living systems as a reactive carbonyl species (RCS). An abnormal degree of FA is known to induce neurodegeneration, cognitive decrease and memory loss owing to the formation of strong cross-link DNA and protein and other molecules. The development of efficient methods for biological FA detection is of great biomedical importance. Although a few one-photon FA fluorescent probes have been reported for imaging in living cells, probes excited by two photons are more suitable for bio-imaging due to their low background fluorescence, less photobleaching, and deep penetration depth. In this study, a two-photon fluorescent probe FATP1 for FA detection and bio-imaging in living cells and tissues was reported. The detection is based on the 2-aza-Cope sigmatropic rearrangement followed by elimination to release the fluorophore, resulting in both one- and two-photon excited fluorescence increase. The probe FATP1 showed a high sensitivity to FA with a detection limit of 0.2 μM. Moreover, FATP1 enabled the two-photon bio-imaging of FA in live HEK-293 cells and tissues with tissue-imaging depths of 40–170 μm. Furthermore, FATP1 could be applied for the monitoring of endogenous FA in live MCF-7 cells, presaging its practical applications in biological systems.
Co-reporter:Huanhuan Fan;Guobei Yan;Dr. Zilong Zhao;Dr. Xiaoxiao Hu;Wenhan Zhang;Hui Liu;Xiaoyi Fu;Ting Fu; Xiao-Bing Zhang; Weihong Tan
Angewandte Chemie International Edition 2016 Volume 55( Issue 18) pp:5477-5482
Publication Date(Web):
DOI:10.1002/anie.201510748
Abstract
Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer–MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.
Co-reporter:Xu-Hua Zhao, Liang Gong, Yuan Wu, Xiao-Bing Zhang, Jun Xie
Talanta 2016 Volume 149() pp:98-102
Publication Date(Web):1 March 2016
DOI:10.1016/j.talanta.2015.11.038
•This assay is a simple, rapid and label-free protocol.•The sensing system displayed high sensitivity and selectivity.•The sensing system can be used for the detection of Pb2+ in urine and paint samples.In this work we use a water-soluble cationic perylene derivative (compound 1) as the G-quadruplex (G4) structure fluorescence indicator to construct a fluorescent biosensor for simple, rapid and label-free detection of Pb2+. In the absence of Pb2+, strong electrostatic interactions between compound 1 and the G-rich DNA probe (PW17) induced the aggregation of compound 1 and resulted in the fluorescence quenching. In the presence of Pb2+, the PW17 formed Pb2+-stabilized G4 structure, which reduced the aggregation of compound 1 and gave rise to high fluorescence. This allowed us to use convenient “mix-and-detect” protocol for quantitative analysis of Pb2+. Since Pb2+ can specially induce PW17 to form compact DNA fold, our proposed biosensor displayed high selectivity for Pb2+. It also exhibited a high sensitivity to Pb2+, with a limit of detection of 5.0 nM observed. Furthermore, the biosensor was applied for the detection of Pb2+ in urine and paint samples, and both showed satisfactory results.Schematic illustration of the selective sensing of Pb2+
Co-reporter:Jing Zhang, Xiao-Yan Zhu, Xiao-Xiao Hu, Hong-Wen Liu, Jin Li, Li−Li Feng, Xia Yin, Xiao-Bing Zhang, and Weihong Tan
Analytical Chemistry 2016 Volume 88(Issue 23) pp:
Publication Date(Web):November 9, 2016
DOI:10.1021/acs.analchem.6b03702
Acute organ injury observed during sepsis, caused by an uncontrolled release of inflammatory mediators, such as lipopolysaccharide (LPS), is quite fatal. The development of efficient methods for early diagnosis of sepsis and LPS-induced acute organ injury in living systems is of great biomedical importance. In living systems, cystathionine γ-lyase (CSE) can be overexpressed due to LPS, and H2Sn can be formed by CSE-mediated cysteine metabolism. Thus, acute organ injury during sepsis may be correlated with H2Sn levels, making accurate detection of H2Sn in living systems of great physiological and pathological significance. In this work, our previously reported fluorescent platform was employed to design and synthesize a FRET-based ratiometric two-photon (TP) fluorescent probe TPR-S, producing a large emission shift in the presence of H2Sn. In this work, a naphthalene derivative two-photon fluorophore was chosen as the energy donor; a rhodol derivative fluorophore served as the acceptor. The 2-fluoro-5-nitrobenzoate group of probe TPR-S reacted with H2Sn and was selectively removed to release the fluorophore, resulting in a fluorescent signal decrease at 448 nm and enhancement at 541 nm. The ratio value of the fluorescence intensity between 541 and 448 nm (I541 nm/I448 nm) varied from 0.13 to 8.12 (∼62-fold), with the H2Sn concentration changing from 0 to 1 mM. The detection limit of the probe was 0.7 μM. Moreover, the probe was applied for imaging H2Sn in living cells, tissues, and organs of LPS-induced acute organ injury, which demonstrated its practical application in complex biosystems as a potential method to achieve early diagnosis of LPS-induced acute organ injury.
Co-reporter:Ting Fu, Songlei Ren, Liang Gong, Hongmin Meng, Liang Cui, Rong-Mei Kong, Xiao-Bing Zhang, Weihong Tan
Talanta 2016 Volume 147() pp:302-306
Publication Date(Web):15 January 2016
DOI:10.1016/j.talanta.2015.10.004
•A label-free biosensor was developed for amplified fluorescence detection of Pb2+.•The strategy provided a universal label-free platform for DNAzyme-based biosensors.•The biosensor was successfully applied in detection of Pb2+ in complex samples.DNAzyme-based catalytic beacons have been widely studied for both in vivo and in vitro molecular detection. However, only a few label-free catalytic beacons with excellent analytical performance have been reported so far. In this work, by combining a catalytic DNAzyme for amplified sensing through enzymatic turnover with cleavage-induced G-quadruplex formation, a label-free DNAzyme biosensor was developed for amplified “turn-on” fluorescence detection of Pb2+ with a detection limit of 3 nM. The method is very competitive compared to many other labeled or label-free methods with or without signal amplification. Due to the inherent specificity of the GR-5 DNAzyme, the method also exhibits excellent selectivity. This biosensor successfully detected Pb2+ in river water samples with high sensitivity and selectivity. Such a method might provide a universal DNAzyme-based sensing platform for sensitive detection of various targets both in environmental and biomedical fields.
Co-reporter:Qiujuan Ma, Junhong Xu, Xiaobing Zhang, Liyi Zhou, Hongwen Liu, Jing Zhang
Sensors and Actuators B: Chemical 2016 Volume 229() pp:434-440
Publication Date(Web):28 June 2016
DOI:10.1016/j.snb.2016.02.005
•A new naphthalene-based two-photon fluorescent probe for thiophenols has been reported.•It exhibits high selectivity and excellent sensitivity with a detection limit of 9.6 nM.•It was successfully used for practical detection of thiophenol in water samples.•It was also successfully used for two-photon imaging of thiophenol in live cells and tissues at a depth of 40–155 μm.A naphthalene-based two-photon fluorescent probe for thiophenols has been reported in this work. The probe can be applied to the quantification of thiophenols with a linear range covering from 2.0 × 10−8 to 7.0 × 10−6 mol L−1. It exhibited a high selectivity and excellent sensitivity with a detection limit of 9.6 nM. Moreover, it was successfully used for practical detection of thiophenol in water samples with a good recovery, and two-photon imaging of thiophenol in live cells and tissues at a depth of 40–155 μm.
Co-reporter:Huanhuan Fan;Guobei Yan;Dr. Zilong Zhao;Dr. Xiaoxiao Hu;Wenhan Zhang;Hui Liu;Xiaoyi Fu;Ting Fu; Xiao-Bing Zhang; Weihong Tan
Angewandte Chemie International Edition 2016 Volume 55( Issue 18) pp:
Publication Date(Web):
DOI:10.1002/anie.201602071
Co-reporter:Huanhuan Fan;Guobei Yan;Dr. Zilong Zhao;Dr. Xiaoxiao Hu;Wenhan Zhang;Hui Liu;Xiaoyi Fu;Ting Fu; Xiao-Bing Zhang; Weihong Tan
Angewandte Chemie 2016 Volume 128( Issue 18) pp:5567-5572
Publication Date(Web):
DOI:10.1002/ange.201510748
Abstract
Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer–MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.
Co-reporter:Huanhuan Fan;Guobei Yan;Dr. Zilong Zhao;Dr. Xiaoxiao Hu;Wenhan Zhang;Hui Liu;Xiaoyi Fu;Ting Fu; Xiao-Bing Zhang; Weihong Tan
Angewandte Chemie 2016 Volume 128( Issue 18) pp:
Publication Date(Web):
DOI:10.1002/ange.201602071
Co-reporter:Liang Gong, Hailan Kuai, Songlei Ren, Xu-Hua Zhao, Shuang-Yan Huan, Xiao-Bing Zhang and Weihong Tan
Chemical Communications 2015 vol. 51(Issue 60) pp:12095-12098
Publication Date(Web):18 Jun 2015
DOI:10.1039/C5CC04442A
By employing DNAzyme as a recognition group and amplifier, and DNA-stabilized silver nanoclusters (DNA/AgNCs) as signal reporters, we reported for the first time a label-free catalytic and molecular beacon as an amplified biosensing platform for highly selective detection of cofactors such as Pb2+ and L-histidine.
Co-reporter:Liang Gong, Zilong Zhao, Yi-Fan Lv, Shuang-Yan Huan, Ting Fu, Xiao-Bing Zhang, Guo-Li Shen and Ru-Qin Yu
Chemical Communications 2015 vol. 51(Issue 6) pp:979-995
Publication Date(Web):14 Oct 2014
DOI:10.1039/C4CC06855F
DNAzymes, screened through in vitro selection, have shown great promise as molecular tools in the design of biosensors and nanodevices. The catalytic activities of DNAzymes depend specifically on cofactors and show multiple enzymatic turnover properties, which make DNAzymes both versatile recognition elements and outstanding signal amplifiers. Combining nanomaterials with unique optical, magnetic and electronic properties, DNAzymes may yield novel fluorescent, colorimetric, surface-enhanced Raman scattering (SERS), electrochemical and chemiluminescent biosensors. Moreover, some DNAzymes have been utilized as functional components to perform arithmetic operations or as “walkers” to move along DNA tracks. DNAzymes can also function as promising therapeutics, when designed to complement target mRNAs or viral RNAs, and consequently lead to down-regulation of protein expression. This feature article focuses on the most significant achievements in using DNAzymes as recognition elements and signal amplifiers for biosensors, and highlights the applications of DNAzymes in logic gates, DNA walkers and nanotherapeutics.
Co-reporter:Jing Zhang, Hong-Wen Liu, Xiao-Xiao Hu, Jin Li, Li-Hui Liang, Xiao-Bing Zhang, and Weihong Tan
Analytical Chemistry 2015 Volume 87(Issue 23) pp:11832
Publication Date(Web):October 30, 2015
DOI:10.1021/acs.analchem.5b03336
Hypoxia plays an important role in tumor progression, and the development of efficient methods for monitoring hypoxic degree in living systems is of great biomedical importance. In the solid tumors, the nitroreductase level is directly corresponded with the hypoxic status. Many one-photon excited fluorescent probes have been developed for hypoxia imaging in tumor cells via the detection of nitroreductase level. However, two-photon excited probes are more suitable for bioimaging. In this work, a two-photon probe 1 for nitroreductase detection and hypoxic status monitoring in living tumor cells and tissues was reported for the first time. The detection is based on the fact that the nitro-group of probe 1 could be selectively reduced to an amino-group by nitroreductase in the presence of reduced NADH, following by a 1,6-rearrangement-elimination to release the fluorophore, resulting in the enhancement of fluorescence. The probe exhibited both one-photon and two-photon excited remarkable fluorescence enhancement (∼70-fold) for nitroreductase, which afforded a high sensitivity for nitroreductase, with a detection limit of 20 ng/mL observed. Moreover, the applications of the probe for fluorescent bioimaging of hypoxia in living cells and two-photon bioimaging in tissues were carried out, with tissue-imaging depths of 70–160 μm observed, which demonstrates its practical application in complex biosystems.
Co-reporter:Liyi Zhou, Qianqian Wang, Xiao-Bing Zhang, and Weihong Tan
Analytical Chemistry 2015 Volume 87(Issue 8) pp:4503
Publication Date(Web):March 26, 2015
DOI:10.1021/acs.analchem.5b00505
Palladium can cause severe skin and eye irritation once it enters the human body. Ratiometric two-photon fluorescent probes can both eliminate interference from environmental factors and realize deep-tissue imaging with improved spatial localization. To quantitatively track Pd2+ in biosystems, we report here a colorimetric and two-photon ratiometric fluorescent probe, termed Np–Rh–Pd, which consists of a two-photon fluorophore (naphthalene derivative with a D-π-A structure) and a rhodamine B dye. The two fluorophores are directly linked to form a two-photon ratiometric fluorescent probe for Pd2+ based on a through-bond energy transfer (TBET) strategy. It exhibits highly efficient energy transfer (90%) with two well-resolved emission peaks (wavelength difference of 100 nm), which could efficiently diminish the cross talk between channels and is especially favorable for ratiometric bioimaging applications. A signal-to-background ratio of 31.2 was observed for the probe, which affords a high sensitivity for Pd2+ with a detection limit of 2.3 × 10–7 M. It was also found that acidity does not affect the fluorescent response of the probe to Pd2+, which is favorable for its applications in practical samples. The probe was further used for fluorescence imaging of Pd2+ ions in live cells and tissue slices under two-photon excitation, which showed significant tissue-imaging depths (90–270 μm) and a high resolution for ratiometric imaging.
Co-reporter:Liyi Zhou, Xiaobing Zhang, Yifan Lv, Chao Yang, Danqing Lu, Yuan Wu, Zhuo Chen, Qiaoling Liu, and Weihong Tan
Analytical Chemistry 2015 Volume 87(Issue 11) pp:5626
Publication Date(Web):April 23, 2015
DOI:10.1021/acs.analchem.5b00691
Photoactivatable probe-based fluorescent imaging has become an efficient and attractive technique for spatiotemporal microscopic studies of biological events. However, almost all previously reported photoactivatable organic probes have been based on hydrosoluble precursors, which have produced water-soluble active fluorophores able to readily diffuse away from the photocleavage site, thereby dramatically reducing spatial resolution. Hydroxyphenylquinazolinone (HPQ), a small organic dye known for its classic luminescence mechanism through excited-state intramolecular proton transfer (ESIPT), shows strong light emission in the solid state, but no emission in solution. In this work, HPQ was employed as a precursor to develop a localizable, photoactivatable two-photon probe (PHPQ) for spatiotemporal bioimaging applications. After photocleavage, PHPQ releases a precipitating HPQ fluorophore which shows both one-photon and two-photon excited yellow-green fluorescence, thereby producing a localizable fluorescence signal that affords high spatial resolution for bioimaging, with more than 200-fold one-photon and 150-fold two-photon fluorescence enhancement.
Co-reporter:Rong Hu, Tao Liu, Xiao-Bing Zhang, Yunhui Yang, Tao Chen, Cuichen Wu, Yuan Liu, Guizhi Zhu, Shuangyan Huan, Ting Fu, and Weihong Tan
Analytical Chemistry 2015 Volume 87(Issue 15) pp:7746
Publication Date(Web):June 26, 2015
DOI:10.1021/acs.analchem.5b01323
A DNAzyme-based ELISA, termed DLISA, was developed as a novel protein enzyme-free, triply amplified platform, combining a catalytic and molecular beacon (CAMB) system with a cation exchange reaction for ultrasensitive multiplex fluorescent immunosorbent assay. Classical ELISA, which employs protein enzymes as biocatalysts to afford amplified signals, suffers from poor stability caused by the irreversible denaturation of these enzymes under harsh conditions, such as heat and acidity. Compared with proteins, nucleic acids are more stable and adaptable, and they can be easily produced using a commercial DNA synthesizer. Moreover, the catalytic and cleavage activities of DNAzyme can be achieved in solution; thus, no enzyme immobilization is needed for detection. Taken together, these attributes suggest that a DNAzyme-based ELISA detection approach will be more robust than current ELISA assays. Importantly, the proposed triply amplified DLISA immunoassay method shows ultrasensitive detection of such targets as human IgG with a detection limit of 2 fg/mL (3 × 10–17 M), which is well within the range of many important disease biomarkers. DLISA can also be used to construct a sensing array for simultaneous multiplexed detection. With these merits, this high-throughput, stable, simple, sensitive, and low-cost multiplex fluorescence immunoassay shows promise for applications in clinical diagnosis.
Co-reporter:Hong-Wen Liu, Xiao-Bing Zhang, Jing Zhang, Qian-Qian Wang, Xiao-Xiao Hu, Peng Wang, and Weihong Tan
Analytical Chemistry 2015 Volume 87(Issue 17) pp:8896
Publication Date(Web):July 31, 2015
DOI:10.1021/acs.analchem.5b02021
Thiophenols, a class of highly toxic and pollutant compounds, are widely used in industrial production. Some aliphatic thiols play important roles in living organisms. Therefore, the development of efficient methods to discriminate thiophenols from aliphatic thiols is of great importance. Although several one-photon fluorescent probes have been reported for thiophenols, two-photon fluorescent probes are more favorable for biological imaging due to its low background fluorescence, deep penetration depth, and so on. In this work, a two-photon fluorescent probe for thiophenols, termed NpRb1, has been developed for the first time by employing 2,4-dinitrobenzene-sulfonate (DNBS) as a recognition unit (also a fluorescence quencher) and a naphthalene-BODIPY-based through-bond energy transfer (TBET) cassette as a fluorescent reporter. The TBET system consists of a D-π-A structured two-photon naphthalene fluorophore and a red-emitting BODIPY. It displayed highly energy transfer efficiency (93.5%), large pseudo-Stokes shifts upon one-photon excitation, and red fluorescence emission (λem = 586 nm), which is highly desirable for bioimaging applications. The probe exhibited a 163-fold thiophenol-triggered two-photon excited fluorescence enhancement at 586 nm. It showed a high selectivity and excellent sensitivity to thiophenols, with a detection limit of 4.9 nM. Moreover, it was successfully applied for practical detection of thiophenol in water samples with a good recovery, two-photon imaging of thiophenol in living cells, and tissues with tissue-imaging depths of 90–220 μm, demonstrating its practical application in environmental samples and biological systems.
Co-reporter:Yifan Lv, Liang Cui, Ruizi Peng, Zilong Zhao, Liping Qiu, Huapei Chen, Cheng Jin, Xiao-Bing Zhang, and Weihong Tan
Analytical Chemistry 2015 Volume 87(Issue 23) pp:11714
Publication Date(Web):October 27, 2015
DOI:10.1021/acs.analchem.5b02654
Here, we propose an efficient strategy for enzyme- and hairpin-free nucleic acid detection called an entropy beacon (abbreviated as Ebeacon). Different from previously reported DNA hybridization/displacement-based strategies, Ebeacon is driven forward by increases in the entropy of the system, instead of free energy released from new base-pair formation. Ebeacon shows high sensitivity, with a detection limit of 5 pM target DNA in buffer and 50 pM in cellular homogenate. Ebeacon also benefits from the hairpin-free amplification strategy and zero-background, excellent thermostability from 20 °C to 50 °C, as well as good resistance to complex environments. In particular, based on the huge difference between the breathing rate of a single base pair and two adjacent base pairs, Ebeacon also shows high selectivity toward base mutations, such as substitution, insertion, and deletion and, therefore, is an efficient nucleic acid detection method, comparable to most reported enzyme-free strategies.
Co-reporter:Hong-Min Meng, Limin Lu, Xu-Hua Zhao, Zhuo Chen, Zilong Zhao, Chan Yang, Xiao-Bing Zhang, and Weihong Tan
Analytical Chemistry 2015 Volume 87(Issue 8) pp:4448
Publication Date(Web):March 20, 2015
DOI:10.1021/acs.analchem.5b00337
Many one-photon fluorescence-based theranostic nanosystems have been developed for simultaneous therapeutic intervention/monitoring for various types of cancers. However, for early diagnosis of cancer, two-photon fluorescence microscopy (TPFM) can realize deep-tissue imaging with higher spatial resolution. In this study, we first report a multiple functional nanoprobe for contrast-enhanced bimodal cellular imaging and targeted therapy. Components of the nanoprobe include (1) two-photon dye-doped mesoporous silica nanoparticles (TPD-MSNs); (2) MnO2 nanosheets that act as a (i) gatekeeper for TPD-MSNs, (ii) quencher for TP fluorescence, and (iii) contrast agent for MRI; (3) cancer cell-targeting aptamers. Guided by aptamers, TPD-MSNs are rapidly internalized into the target cells. Next, intracellular glutathione reduces MnO2 to Mn2+ ions, resulting in contrast-enhanced TP fluorescence and magnetic resonance signal for cellular imaging. Meanwhile, preloaded doxorubicin and Chlorin e6 are released for chemotherapy and photodynamic therapy, respectively, with a synergistic effect and significantly enhanced therapeutic efficacy.
Co-reporter:Liping Kang, Bin Yang, Xiaobing Zhang, Liang Cui, Hongmin Meng, Lei Mei, Cuichen Wu, Songlei Ren, Weihong Tan
Analytica Chimica Acta 2015 Volume 879() pp:91-96
Publication Date(Web):16 June 2015
DOI:10.1016/j.aca.2015.03.030
•A novel mass amplification strategy was developed.•This strategy can be used for sensitive detection of small molecule in complex biological samples.•Excellent performances in adenosine measurement with aptamer-based FP probe.Fluorescence polarization (FP) assays incorporated with fluorophore-labeled aptamers have attracted great interest in recent years. However, detecting small molecules through the use of FP assays still remains a challenge because small-molecule binding only results in negligible changes in the molecular weight of the fluorophore-labeled aptamer. To address this issue, we herein report a fluorescence polarization (FP) aptamer assay that incorporates a novel signal amplification strategy for highly sensitive detection of small molecules. In the absence of adenosine, our model target, free FAM-labeled aptamer can be digested by nuclease, resulting in the release of FAM-labeled nucleotide segments from the dT-biotin/streptavidin complex with weak background signal. However, in the presence of target, the FAM-labeled aptamer–target complex protects the FAM-labeled aptamer from nuclease cleavage, allowing streptavidin to act as a molar mass amplifier. The resulting increase in molecular mass and FP intensity of the aptamer–target complex provides improved sensitivity for concentration measurement. The probe could detect adenosine from 0.5 μM to 1000 μM, with a detection limit of 500 nM, showing that the sensitivity of the probe is superior to aptamer-based FP approaches previously reported for adenosine. Importantly, FP could resist environmental interferences, making it useful for complex biological samples without any tedious sample pretreatments. Our results demonstrate that this dual-amplified, aptamer-based strategy can be used to design fluorescence polarization probes for rapid, sensitive, and selective measurement of small molecules in complicated biological environment.
Co-reporter:Qianqian Wang, Liyi Zhou, Liping Qiu, Danqing Lu, Yongxiang Wu and Xiao-Bing Zhang
Analyst 2015 vol. 140(Issue 16) pp:5563-5569
Publication Date(Web):09 Jun 2015
DOI:10.1039/C5AN00683J
Lysosomes are acidic organelles (approximately pH 4.5–5.5) and tracking the changes in lysosomal pH is of great biological importance. To address this issue, quite a few of fluorescent probes have been developed. However, few of these probes can realize the tracking of dynamic changes in lysosomal pH. Herein, we report a new lysosome-targeted ratiometric fluorescent probe (FR-Lys) by hybridizing morpholine with a xanthane derivative and an o-hydroxy benzoxazole group. In this probe, the morpholine group serves as a targeting unit for lysosome, the xanthane derivative exhibits a pH-modulated open/close reaction of the spirocycle, while the o-hydroxy benzoxazole moiety shows a pH modulated excited-state intramolecular proton transfer (ESIPT) process. Such a design affords the probe a ratiometric fluorescence response towards pH with pH values ranging from 4.0 to 6.3. The response of the probe to pH was fast and reversible with high selectivity. Moreover, this probe possesses further advantages such as easy synthesis, high photostability and low cytotoxicity. These features are favorable for tracking dynamic pH changes in biosystems. It was then applied for dynamic imaging pH changes in lysosomes with satisfactory results.
Co-reporter:Xu-Hua ZHAO, Hong-Min MENG, Liang GONG, Li-Ping QIU, Xiao-Bing ZHANG, Wei-Hong TAN
Chinese Journal of Analytical Chemistry 2015 Volume 43(Issue 11) pp:1611-1619
Publication Date(Web):November 2015
DOI:10.1016/S1872-2040(15)60873-8
DNAzymes, screened through in vitro selection, were artificial nucleic acids with catalytic function. They could cleave specific substrates in the presence of cofactors with unique characteristics, such as high catalytic activity, high specificity for cofactors, excellent stability, and easy to synthesize and modify. The combination of DNAzymes with nanomaterials could retain the DNAzyme activity and realize the functional integration of recognition and signal transduction, promoting rapid development of biosensors. In the current paper, we have mainly reviewed the recent progress of DNAzyme-nanomaterial based biosensors, and the nanomaterials included gold nanoparticles, graphene, quantum dots, magnetic nanomaterials, and so on.This paper reviewed the recent progress of DNAzyme-nanomaterial-based biosensors, and the nanomaterials included gold nanoparticles, graphene, quantum dots, magnetic nanomaterials etc. The combination of DNAzymes with nanomaterials could retain the DNAzyme activity and realize the functional integration of recognition and signal transduction, promoting rapid development of biosensors.
Co-reporter:Lei Mei;Guizhi Zhu;Liping Qiu;Cuichen Wu;Huapei Chen;Hao Liang
Nano Research 2015 Volume 8( Issue 11) pp:3447-3460
Publication Date(Web):2015 November
DOI:10.1007/s12274-015-0841-8
Cancer chemotherapy has been limited by its side effects and multidrug resistance (MDR), the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers (NFs) for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin (Dox)-binding DNA for drug delivery. NF sizes are tunable (down to ∼200 nm in diameter), and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity (71.4%, wt/wt). Although the Doxloaded NFs (NF-Dox) are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.
Co-reporter:Huijie Zhu;Jin Li; Xiao-Bing Zhang; Mao Ye; Weihong Tan
ChemMedChem 2015 Volume 10( Issue 1) pp:39-45
Publication Date(Web):
DOI:10.1002/cmdc.201402312
Abstract
Aptamers are emerging as promising therapeutic agents and recognition elements. In particular, cell-SELEX (systematic evolution of ligands by exponential enrichment) allows in vitro selection of aptamers selective to whole cells without prior knowledge of the molecular signatures on the cell surface. The advantage of aptamers is their high affinitiy and binding specificity towards the target. This Minireview focuses on single-stranded (ss) oligonucleotide (DNA or RNA)-based aptamers as cancer therapeutics/theranostics. Specifically, aptamer–nanomaterial conjugates, aptamer–drug conjugates, targeted phototherapy and targeted biotherapy are covered in detail. In reviewing the literature, the potential of aptamers as delivery systems for therapeutic and imaging applications in cancer is clear, however, major challenges remain to be resolved, such as the poorly understood pharmacokinetics, toxicity and off-target effects, before they can be fully exploited in a clinical setting.
Co-reporter:Cheng Jin;Jing Zheng;Chunmei Li;Liping Qiu
Journal of Molecular Evolution 2015 Volume 81( Issue 5-6) pp:162-171
Publication Date(Web):2015/12/01
DOI:10.1007/s00239-015-9716-6
Conventional diagnostics for cancer rely primarily on anatomical techniques. However, these techniques cannot monitor the changes at the molecular level in normal cells, which possibly signal the onset of cancer at its very earliest stages. For accurate prediction of the carcinogenesis at the molecular level, targeting ligands have been used in combination with imaging probes to monitor this biological process. Among these targeting ligands, aptamers have high binding affinity to various targets ranging from small molecules to whole organisms, and, hence, exceptional recognition ability. Many recent studies have been reported on aptamer-based molecular imaging, clearly indicating its clinical and diagnostic utility. In this review, we will discuss some key results of these studies.
Co-reporter:Hao Liang, Xiao-Bing Zhang, Yifan Lv, Liang Gong, Ruowen Wang, Xiaoyan Zhu, Ronghua Yang, and Weihong Tan
Accounts of Chemical Research 2014 Volume 47(Issue 6) pp:1891-1901
Publication Date(Web):April 29, 2014
DOI:10.1021/ar500078f
DNA self-assembled nanomaterials contain several properties of both DNA and nanomaterials. Compared with DNA–nanomaterial complexes, DNA self-assembled nanomaterials more closely resemble living beings, and therefore they have lower cytotoxicity at high concentrations. Functional DNA self-assemblies also have high density of DNA for multivalent reaction and three-dimensional nanostructures for cell uptake. Now and in the future, we envision the use of DNA bases in making designer molecules for many challenging applications confronting chemists. With the further development of artificial DNA bases using smart organic synthesis, DNA macromolecules based on elegant molecular assembly approaches are expected to achieve great diversity, additional versatility, and advanced functions.
Co-reporter:Zhi-Ling Song ; Zhuo Chen ; Xia Bian ; Li-Yi Zhou ; Ding Ding ; Hao Liang ; Yu-Xiu Zou ; Shan-Shan Wang ; Long Chen ; Chao Yang ; Xiao-Bing Zhang ;Weihong Tan
Journal of the American Chemical Society 2014 Volume 136(Issue 39) pp:13558-13561
Publication Date(Web):September 18, 2014
DOI:10.1021/ja507368z
Noble metals, especially gold, have been widely used in plasmon resonance applications. Although silver has a larger optical cross section and lower cost than gold, it has attracted much less attention because of its easy corrosion, thereby degrading plasmonic signals and limiting its applications. To circumvent this problem, we report the facile synthesis of superstable AgCu@graphene (ACG) nanoparticles (NPs). The growth of several layers of graphene onto the surface of AgCu alloy NPs effectively protects the Ag surface from contamination, even in the presence of hydrogen peroxide, hydrogen sulfide, and nitric acid. The ACG NPs have been utilized to enhance the unique Raman signals from the graphitic shell, making ACG an ideal candidate for cell labeling, rapid Raman imaging, and SERS detection. ACG is further functionalized with alkyne-polyethylene glycol, which has strong Raman vibrations in the Raman-silent region of the cell, leading to more accurate colocalization inside cells. In sum, this work provides a simple approach to fabricate corrosion-resistant, water-soluble, and graphene-protected AgCu NPs having a strong surface plasmon resonance effect suitable for sensing and imaging.
Co-reporter:Guo-Jiang Mao, Xiao-Bing Zhang, Xue-Lin Shi, Hong-Wen Liu, Yong-Xiang Wu, Li-Yi Zhou, Weihong Tan and Ru-Qin Yu
Chemical Communications 2014 vol. 50(Issue 43) pp:5790-5792
Publication Date(Web):01 Apr 2014
DOI:10.1039/C4CC01440E
A novel coumarin-based fluorescent probe, P-CM, for quantitative detection of nitroxyl (HNO) was developed. P-CM exhibits a selective response to HNO over other biological reductants and was also applied for quantitative detection of HNO in bovine serum with satisfactory results.
Co-reporter:Yong-Xiang Wu, Jun-Bin Li, Li-Hui Liang, Dan-Qing Lu, Jing Zhang, Guo-Jiang Mao, Li-Yi Zhou, Xiao-Bing Zhang, Weihong Tan, Guo-Li Shen and Ru-Qin Yu
Chemical Communications 2014 vol. 50(Issue 16) pp:2040-2042
Publication Date(Web):20 Dec 2013
DOI:10.1039/C3CC48649D
The water-soluble CP was conjugated with a rhodamine spirolactam for the first time to develop a new FRET-based ratiometric fluorescence sensing platform (CP 1) for intracellular metal-ion probing. CP 1 exhibits excellent water-solubility with two well-resolved emission peaks, which benefit ratiometric intracellular imaging applications.
Co-reporter:Yong-Xiang Wu, Xiao-Bing Zhang, Jun-Bin Li, Cui-Cui Zhang, Hao Liang, Guo-Jiang Mao, Li-Yi Zhou, Weihong Tan, and Ru-Qin Yu
Analytical Chemistry 2014 Volume 86(Issue 20) pp:10389
Publication Date(Web):September 22, 2014
DOI:10.1021/ac502863m
Pyrene excimer possesses a large Stokes shift and long fluorescence lifetime and has been widely applied in developing time-resolved biosensing systems to solve the autofluorescence interference problems in biological samples. However, only a few of pyrene excimer-based small molecular probes have been reported so far. Ratiometric probes, on the other hand, can eliminate interferences from environmental factors such as instrumental efficiency and environmental conditions by a built-in correction of the dual emission bands but are ineffective for endogenous autofluorescence in biosystems. In this work, by combining the advantages of time-resolved fluorescence technique with ratiometric probe, we reported a bispyrene–fluorescein hybrid FRET cassette (PF) as a novel ratiometric time-resolved sensing platform for bioanalytical applications, with pH chosen as a biorelated target. The probe PF showed a fast, highly selective, and reversible ratiometric fluorescence response to pH in a wide range from 3.0 to 10.0 in buffered solution. By employing time-resolved fluorescence technique, the pH-induced fluorescence signal of probe PF can be well-discriminated from biological autofluorescence background, which enables us to detect pH in a range of 4.0–8.0 in cell media within a few seconds. It has also been preliminarily applied for ratiometric quantitative monitoring of pH changes in living cells with satisfying results. Since many fluorescein-based fluorescence probes have been developed, our strategy might find wide applications in design ratiometric time-resolved probes for detection of various biorelated targets.
Co-reporter:Hong-Min Meng, Zhen Jin, Yifan Lv, Chan Yang, Xiao-Bing Zhang, Weihong Tan, and Ru-Qin Yu
Analytical Chemistry 2014 Volume 86(Issue 24) pp:12321
Publication Date(Web):November 17, 2014
DOI:10.1021/ac503617n
Glutathione (GSH) serves vital cellular biological functions, and its abnormal levels are associated with many diseases. To better understand its physiological and pathological functions, efficient methods for monitoring of GSH in living systems are desired. Although quite a few small molecule-based and nanomaterial-based one photon fluorescence probes have been reported for GSH, two-photon (TP) probes, especially nanoprobes with good membrane permeability, are more favorable for bioimaging applications, since TP fluorescence imaging can provide improved spatial localization and increased imaging depth. In this work, we for the first time reported a “turn-on” TP fluorescence nanoprobe for efficient detection of GSH in aqueous solutions and TP excited fluorescence imaging of GSH in living cells and tissues. The nanoprobe consists of two-photon mesoporous silica nanoparticles (TP-MSNs) with a large TP excitation action cross-section (Φδ) value of 103 GM and MnO2 nanosheets, which show intense and broad optical absorption and could act as efficient quenchers for TP fluorescence. In the sensing system, the negatively charged MnO2 nanosheets are adsorbed on the positively charged MSNs through electrostatic interaction, resulting in efficient quenching of their fluorescence, with very low background fluorescence observed. The addition of GSH could reduce MnO2 into Mn2+, lead to the decomposition of the MnO2 nanosheets, and thereby result in remarkable enhancement of both one photon and TP excited fluorescence of the nanosystem. The nanoprobe shows a highly sensitive response to GSH in aqueous solutions, with a detection limit of 200 nM achieved. It also exhibits a high selectivity toward GSH relative to other biomolecules and electrolytes, with good membrane permeability and excellent biocompatibility. The nanoprobe was successfully applied in monitoring the change of the intracellular GSH in living cells and tissues via TP fluorescence imaging, demonstrating its value of practical application in biological systems.
Co-reporter:Cui-Cui Zhang, Yijun Gong, Yuan Yuan, Aili Luo, Weijun Zhang, Jing Zhang, Xiaobing Zhang and Weihong Tan
Analytical Methods 2014 vol. 6(Issue 2) pp:609-614
Publication Date(Web):20 Nov 2013
DOI:10.1039/C3AY41484A
In this paper, by employing a rigid xanthene scaffold as a bridge, we for the first time report a cofacial bispyrene derivative DPH as an efficient ratiometric fluorescent excimer probe for hypochlorite (OCl−). The probe is comprised of a rigid xanthene scaffold and two parallel pyrenes, which are linked by an OCl−-sensitive dicarboxylic acid hydrazide group. The introduction of OCl−, however, will induce oxidation of the dicarboxylic acid hydrazide moiety into a diimide group, and the subsequent hydrolysis of the diimide, to give 1-pyrenecarboxylic acid which exhibits a monomer emission at about 380 nm, with its intensity increasing with the addition of increased concentration of OCl−. Meanwhile, the excimer emission intensity gradually decreases. Such a ratiometric fluorescent response of the probe affords a high sensitivity to OCl−, with a linear response concentration range of 1 to 300 μM, and a detection limit of 0.35 μM for OCl−. It also shows a high selectivity for OCl− with no interference observed from other common anions and small molecules. Moreover, it can also act as a colorimetric probe for OCl− due to the cyan-to-blue fluorescence color change. It has been preliminarily used for practical detection of OCl− in river water samples with satisfying results.
Co-reporter:Xue-Lin Shi, Guo-Jiang Mao, Xiao-Bing Zhang, Hong-Wen Liu, Yi-Jun Gong, Yong-Xiang Wu, Li-Yi Zhou, Jing Zhang, Weihong Tan
Talanta 2014 Volume 130() pp:356-362
Publication Date(Web):1 December 2014
DOI:10.1016/j.talanta.2014.07.030
•A new fluorescent probe was developed for imaging lysosomal pH changes with excellent analytical performances.•RM can highly selectively stain lysosomes in live cells.•RM can monitor the chloroquine-induced and dexamethasone-induced lysosomal pH changes.Intracellular pH plays a pivotal role in various biological processes. In eukaryotic cells, lysosomes contain numerous enzymes and proteins exhibiting a variety of activities and functions at acidic pH (4.5–5.5), and abnormal variation in the lysosomal pH causes defects in lysosomal function. Thus, it is important to investigate lysosomal pH in living cells to understand its physiological and pathological processes. In this work, we designed a one-step synthesized rhodamine derivative (RM) with morpholine as a lysosomes tracker, to detect lysosomal pH changes with high sensitivity, high selectivity, high photostability and low cytotoxicity. The probe RM shows a 140-fold fluorescence enhancement over a pH range from 7.4 to 4.5 with a pKa value of 5.23. Importantly, RM can detect the chloroquine-induced lysosomal pH increase and monitor the dexamethasone-induced lysosomal pH changes during apoptosis in live cells. All these features demonstrate its value of practical application in biological systems.
Co-reporter:Hong-Min Meng, Xiaobing Zhang, Yifan Lv, Zilong Zhao, Nan-Nan Wang, Ting Fu, Huanhuan Fan, Hao Liang, Liping Qiu, Guizhi Zhu, and Weihong Tan
ACS Nano 2014 Volume 8(Issue 6) pp:6171
Publication Date(Web):May 7, 2014
DOI:10.1021/nn5015962
Functional nucleic acid (FNA)-based sensing systems have been developed for efficient detection of a wide range of biorelated analytes by employing DNAzymes or aptamers as recognition units. However, their intracellular delivery has always been a concern, mainly in delivery efficiency, kinetics, and the amount of delivered FNAs. Here we report a DNA dendrimer scaffold as an efficient nanocarrier to deliver FNAs and to conduct in situ monitoring of biological molecules in living cells. A histidine-dependent DNAzyme and an anti-ATP aptamer were chosen separately as the model FNAs to make the FNA dendrimer. The FNA-embedded DNA dendrimers maintained the catalytic activity of the DNAzyme or the aptamer recognition function toward ATP in the cellular environment, with no change in sensitivity or specificity. Moreover, these DNA dendrimeric nanocarriers show excellent biocompatibility, high intracellular delivery efficiency, and sufficient stability in a cellular environment. This FNA dendrimeric nanocarrier may find a broad spectrum of applications in biomedical diagnosis and therapy.Keywords: aptamer; DNA dendrimer; DNAzyme; functional nucleic acids; intracellular molecular sensing; nanocarrier
Co-reporter:Tao Liu, Rong Hu, Yi-Fan Lv, Yuan Wu, Hao Liang, Shuang-Yan Huan, Xiao-Bing Zhang, Weihong Tan, Ru-Qin Yu
Biosensors and Bioelectronics 2014 Volume 58() pp:320-325
Publication Date(Web):15 August 2014
DOI:10.1016/j.bios.2014.02.083
•Perylene 1 can act as a broad-spectrum and label-free quencher.•The probe shows a high sensitivity to nucleases activity.•The perylene quencher does not affect the activity of nuclease.Fluorescent sensing systems based on the quenching of fluorophores have found wide applications in bioassays. An efficient quencher will endow the sensing system a high sensitivity. The frequently used quenchers are based on organic molecules or nanomaterials, which usually need tedious synthesizing and modifying steps, and exhibit different quenching efficiencies to different fluorophores. In this work, we for the first time report that aggregated perylene derivative can serve as a broad-spectrum and label-free quencher that is able to efficiently quench a variety of fluorophores, such as green, red and far red dyes labeled on DNA. By choosing nucleases as model biomolecules, such a broad-spectrum quencher was then employed to construct a multiplexed bioassay platform through a label-free manner. Due to the high quenching efficiency of the aggregated perylene, the proposed platform could detect nuclease with high sensitivity, with a detection limit of 0.03 U/mL for EcoRV, and 0.05 U/mL for EcoRI. The perylene quencher does not affect the activity of nuclease, which makes it possible to design post-addition type bioassay platform. Moreover, the proposed platform allows simultaneous and multicolor analysis of nucleases in homogeneous solution, demonstrating its value of potential application in rapid screening of multiple bio-targets.
Co-reporter:Cuichen Wu ; Da Han ; Tao Chen ; Lu Peng ; Guizhi Zhu ; Mingxu You ; Liping Qiu ; Kwame Sefah ; Xiaobing Zhang ;Weihong Tan
Journal of the American Chemical Society 2013 Volume 135(Issue 49) pp:18644-18650
Publication Date(Web):November 18, 2013
DOI:10.1021/ja4094617
The ability to self-assemble one-dimensional DNA building blocks into two- and three-dimensional nanostructures via DNA/RNA nanotechnology has led to broad applications in bioimaging, basic biological mechanism studies, disease diagnosis, and drug delivery. However, the cellular uptake of most nucleic acid nanostructures is dependent on passive delivery or the enhanced permeability and retention effect, which may not be suitable for certain types of cancers, especially for treatment in vivo. To meet this need, we have constructed a multifunctional aptamer-based DNA nanoassembly (AptNA) for targeted cancer therapy. In particular, we first designed various Y-shaped functional DNA domains through predesigned base pair hybridization, including targeting aptamers, intercalated anticancer drugs, and therapeutic antisense oligonucleotides. Then these functional DNA domains were linked to an X-shaped DNA core connector, termed a building unit, through the complementary sequences in the arms of functional domains and connector. Finally, hundreds (∼100–200) of these basic building units with 5′-modification of acrydite groups were further photo-cross-linked into a multifunctional and programmable aptamer-based nanoassembly structure able to take advantage of facile modular design and assembly, high programmability, excellent biostability and biocompatibility, as well as selective recognition and transportation. With these properties, AptNAs were demonstrated to have specific cytotoxic effect against leukemia cells. Moreover, the incorporation of therapeutic antisense oligonucleotides resulted in the inhibition of P-gp expression (a drug efflux pump to increase excretion of anticancer drugs) as well as a decrease in drug resistance. Therefore, these multifunctional and programmable aptamer-based DNA nanoassemblies show promise as candidates for targeted drug delivery and cancer therapy.
Co-reporter:Ting Fu, Xu-Hua Zhao, Hua-Rong Bai, Zi-Long Zhao, Rong Hu, Rong-Mei Kong, Xiao-Bing Zhang, Weihong Tan and Ru-Qin Yu
Chemical Communications 2013 vol. 49(Issue 59) pp:6644-6646
Publication Date(Web):05 Jun 2013
DOI:10.1039/C3CC43054E
Taking advantage of the super-quenching effect of the cationic perylene derivative on adjacent fluorophores, we for the first time reported a DNAzyme–perylene complex-based strategy for constructing fluorescence catalytic biosensors with improved sensitivity.
Co-reporter:Guo-Jiang Mao, Tian-Tian Wei, Xu-Xiang Wang, Shuang-yan Huan, Dan-Qing Lu, Jing Zhang, Xiao-Bing Zhang, Weihong Tan, Guo-Li Shen, and Ru-Qin Yu
Analytical Chemistry 2013 Volume 85(Issue 16) pp:7875
Publication Date(Web):July 18, 2013
DOI:10.1021/ac401518e
H2S is the third endogenously generated gaseous signaling compound and has also been known to involve a variety of physiological processes. To better understand its physiological and pathological functions, efficient methods for monitoring of H2S in living systems are desired. Although quite a few one photon fluorescence probes have been reported for H2S, two-photon (TP) probes are more favorable for intracellular imaging. In this work, by employing a donor-π-acceptor-structured naphthalene derivative as the two-photon fluorophore and an azide group as the recognition unit, we reported a new two-photon bioimaging probe 6-(benzo[d]thiazol-2′-yl)-2-azidonaphthalene (NHS1) for H2S with improved sensitivity. The probe shows very low background fluorescence in the absence of H2S. In the presence of H2S, however, a significant enhancement for both one photon and TP excited fluorescence were observed, resulting in a high sensitivity to H2S in aqueous solutions with a detection limit of 20 nM observed, much lower than the previously reported TP probe. The probe also exhibits a wide linear response concentration range (0–5 μM) to H2S with high selectivity. All these features are favorable for direct monitoring of H2S in complex biological samples. It was then applied for direct TP imaging of H2S in living cells with satisfactory sensitivity, demonstrating its value of practical application in biological systems.
Co-reporter:Bin Yang, Xiao-Bing Zhang, Li-Ping Kang, Guo-Li Shen, Ru-Qin Yu, and Weihong Tan
Analytical Chemistry 2013 Volume 85(Issue 23) pp:11518
Publication Date(Web):October 25, 2013
DOI:10.1021/ac402781g
Aptamer-based fluorescence anisotropy (FA) assays have attracted great interest in recent years. However, a key factor that determines FA value is molar mass, thus limiting the utility of this assay for the detection of small molecules. To solve this problem, streptavidin, as a molar mass amplifier, was used in a hybridization chain reaction (HCR) to construct a target-triggered cyclic assembly of DNA–protein hybrid nanowires for highly sensitive detection of small molecules by fluorescence anisotropy. In this assay, one blocking DNA strand is released by target–aptamer recognition. The DNA then serves as an initiator to trigger enzyme-free autonomous cross-opening of hairpin probes via HCR to form a DNA nanowire for further assembly of streptavidin. Using adenosine triphosphate (ATP) as the small molecule target, this novel dual-amplified, aptamer-based FA assay affords high sensitivity with a detection limit of 100 nM. This limit of detection (LOD) is much lower than that of the disassembly approach without HCR amplification or the assembly strategy without streptavidin. In contrast to the previous turn-off disassembly approaches based on nonspecific interactions between the aptamer probe and amplification moieties, the proposed aptamer-based FA assay method exhibits a turn-on response to ATP, which can increase sensing reliability and reduce the risk of false hits. Moreover, because of its resistance to environmental interferences, this FA assay has been successfully applied for direct detection of 0.5 μM ATP in complex biological samples, including cell media, human urine, and human serum, demonstrating its practicality in real complex biological systems.
Co-reporter:Xu-Hua Zhao, Liang Gong, Xiao-Bing Zhang, Bin Yang, Ting Fu, Rong Hu, Weihong Tan, and Ruqin Yu
Analytical Chemistry 2013 Volume 85(Issue 7) pp:3614
Publication Date(Web):February 14, 2013
DOI:10.1021/ac303457u
DNAzymes have been widely applied as signal amplifiers for enzyme-free and highly sensitive detection of DNA. A few of them have also been employed for amplified detection of other biomolecules via a target-triggered assembly of split or mutated DNAzyme strategy. However, most of these designs adopt Mg2+-dependent DNAzyme as the catalytic unit, which suffered from low catalytic cleavage activity. Meanwhile, some DNAzymes with high catalytic activity are not suitable for these designs because the slight modification of the catalytic core might results in remarkably decreased or even no catalytic activity of these DNAzymes. On the basis of DNAzyme topological effect or the terminal protection of small-molecule-linked DNA, we developed two versatile sensing platforms for amplified detection of different biotargets. Since no modification is necessary for the catalytic core of the DNAzyme in these designs, they can employ any DNAzyme with high catalytic activity as amplified unit, which affords a high amplified efficiency for the sensing platform. A catalytic and molecular beacon design was further employed to realize the true enzymatic multiple turnover of DNAzyme. These designs together allow a high sensitivity for the biotargets, resulting in a detection limit of 20 pM, 0.2 U/mL, and 1 ng/mL for target DNA, DNA adenine methylation methyltransferase (Dam MTase), and streptavidin, respectively, much lower than previously reported biosensors. In addition, the proposed sensing strategy is versatile. By conjugating with various recognition units, it can be employed to detect a wide range of biotargets, varying from nucleic acids to proteins with high sensitivity.
Co-reporter:De-Xun Xie, Zhao-Jin Ran, Zhen Jin, Xiao-Bing Zhang, De-Lie An
Dyes and Pigments 2013 Volume 96(Issue 2) pp:495-499
Publication Date(Web):February 2013
DOI:10.1016/j.dyepig.2012.10.007
A aggregation-induced emission-based fluorescent probe 1 for Zn2+ was designed and simply synthesized by condensation of salicylaldehyde with aqueous hydrazine. The experimental conditions were first optimized. It was found that N, N-Dimethylformamide (DMF) was the best solvent for the Zn2+-triggered aggregation of compound 1 compared with other solvents. The emission intensity was gradually increased, accompanied by the simultaneous red shift of the maximum emission peak with increasing Zn2+ concentrations. A red shift about 45 nm was achieved when Zn2+ concentration is 100 μM. Compared with other Zn2+ fluorescent sensors based on aggregation-induced emission (AIE), compound 1 can detect a lower concentration of Zn2+ with a detection limit of 0.1 μM. Compound 1 also exhibited good selectivity toward Zn2+. The aggregation was verified by the dynamic light scattering (DLS) results, with a Zn2+ concentration-dependent size observed. It was also directly confirmed by TEM analyses.Highlights► The sensing mechanism is different from most previously reported. ► Compound 1 is able to be synthesized with relative ease. ► Compound 1 exhibits high sensitivity and good selectivity toward Zn2+.
Co-reporter:Tian-Tian Wei, Jing Zhang, Guo-Jiang Mao, Xiao-Bing Zhang, Zhao-Jin Ran, Weihong Tan and Ruqin Yu
Analytical Methods 2013 vol. 5(Issue 16) pp:3909-3914
Publication Date(Web):15 May 2013
DOI:10.1039/C3AY40354H
Aggregation-induced emission (AIE) dyes show different emission mechanism from traditional dyes, which were found to be nonluminescent in the solution state and emissive in the aggregate state, and have been well employed to design turn-on fluorescent probes for various targets. In this paper, we report for the first time a tetraphenylethylene-based AIE probe 1 for Al3+, which employed two diethylenetriamine units as the recognition ligand for Al3+. In the presence of Al3+, a large fluorescence enhancement was achieved for probe 1, which together with the low background fluorescence of free probe 1 allow for high sensitivity for Al3+, with a dynamic range from 2.0 × 10−6 to 1.1 × 10−5 M observed, and a detection limit of 5 × 10−7 M for Al3+. The proposed probe shows high selectivity to Al3+. UV-vis absorption spectra experiments and dynamic light scattering measurements were performed to verify the AIE sensing mechanism of probe 1. Moreover, a 1:1 stoichiometry was estimated for the 1–Al3+ complex via fluorescence Job's method.
Co-reporter:Tao Chen;Cuichen Sam Wu;Elizabeth Jimenez;Dr. Zhi Zhu;Joshua G. Dajac;Dr. Mingxu You;Da Han;Dr. Xiaobing Zhang;Dr. Weihong Tan
Angewandte Chemie International Edition 2013 Volume 52( Issue 7) pp:2012-2016
Publication Date(Web):
DOI:10.1002/anie.201209440
Co-reporter:Dr. Zilong Zhao;Hongmin Meng;Nannan Wang;Michael J. Donovan;Ting Fu;Dr. Mingxu You; Zhuo Chen; Xiaobing Zhang; Weihong Tan
Angewandte Chemie International Edition 2013 Volume 52( Issue 29) pp:7487-7491
Publication Date(Web):
DOI:10.1002/anie.201302557
Co-reporter:Dr. Zilong Zhao;Hongmin Meng;Nannan Wang;Michael J. Donovan;Ting Fu;Dr. Mingxu You; Zhuo Chen; Xiaobing Zhang; Weihong Tan
Angewandte Chemie 2013 Volume 125( Issue 29) pp:7635-7639
Publication Date(Web):
DOI:10.1002/ange.201302557
Co-reporter:Tao Chen;Cuichen Sam Wu;Elizabeth Jimenez;Dr. Zhi Zhu;Joshua G. Dajac;Dr. Mingxu You;Da Han;Dr. Xiaobing Zhang;Dr. Weihong Tan
Angewandte Chemie 2013 Volume 125( Issue 7) pp:2066-2070
Publication Date(Web):
DOI:10.1002/ange.201209440
Co-reporter:Bin Yang, Xiao-Bing Zhang, Wei-Na Liu, Rong Hu, Weihong Tan, Guo-Li Shen, Ru-Qin Yu
Biosensors and Bioelectronics 2013 Volume 48() pp:1-5
Publication Date(Web):15 October 2013
DOI:10.1016/j.bios.2013.03.044
•A colorimetric probe was developed for label-free detection of Au3+.•This gold nanoparticles probe was based on thiol masking reaction.•The probe exhibits a high sensitivity with a detection limit of 50 nM.•A tunable response range could be obtained for Au3+ by varying the amount of Cys.Gold nanoparticles-based colorimetric assay possesses several unique advantages, and has been applied for a wide range of targets, varying from nucleic acids to different metal ions. However, due to the lack of proper coordinating ligand, gold nanoparticles-based colorimetric sensing system for Au3+ has not been developed so far. It is well-known that Au3+ could induce the oxidation transition of thiol compounds to disulfide compounds. In this article, for the first time we converted such thiol masking reaction into colorimetric sensing system for label-free detection of Au3+ via a target-controlled aggregation of nanoparticles strategy. In the new proposed sensing system, fluorosurfactant-capped gold nanoparticles were chosen as signal reporter units, while an Au3+-triggered oxidation of cysteine (Cys), which inhibited the aggregation of gold nanoparticles, acted as the recognition unit. By varying the amount of Cys, a tunable response range accompanied with different windows of color change could be obtained for Au3+, illustrating the universality of the sensing system for Au3+ samples with different sensitivity requirements. Under optimized condition, the proposed sensing system exhibits a high sensitivity towards Au3+ with a detection limit of 50 nM, which is lower than previously reported spectroscopic methods. It has also been applied for detection of Au3+ in practical water samples with satisfactory result.
Co-reporter:Li-Min Lu, Xin-Lan Qiu, Xiao-Bing Zhang, Guo-Li Shen, Weihong Tan, Ru-Qin Yu
Biosensors and Bioelectronics 2013 Volume 45() pp:102-107
Publication Date(Web):15 July 2013
DOI:10.1016/j.bios.2013.01.065
The self-assembly of cyclodextrin (CD) functionalized graphene (GR) and adamantane-modified horseradish peroxidase (HRP-ADA) by host–guest supramolecular interaction into novel nanostructures in aqueous solution is reported in the present study. Electrochemical impedance spectroscopy and cyclic voltammetry were applied to characterize the self-assembly process and study the electrochemical behaviors of the immobilized proteins. UV–vis spectra indicated that the native structure of HRP was maintained after the assembly, implying good biocompatibility of CD-functionalized GR (CD-GR). Furthermore, the HRP-ADA/CD-GR composites were utilized for the fabrication of enzyme electrodes (HRP-ADA/CD-GR electrodes). The proposed biosensor showed good reproducibility and high sensitivity to H2O2 with the detection limit of 0.1 μM. In the range of 0.7–35 μM, the catalytic reduction current of H2O2 was proportional to H2O2 concentration.Highlights► Cyclodextrin-graphene nanocomposite was synthesized by a simple chemical strategy. ► HRP was immobilized on the nanocomposite matrix by host–guest supramolecular interactions. ► Immobilized HRP can communicate electrons with electrode efficiently. ► Biosensor exhibited good analytical performance toward the quantification of H2O2. ► Biosensor can be successfully applicable for practical H2O2 detection.
Co-reporter:Rong Hu, Ya-Ru Liu, Xiao-Bing Zhang, Weihong Tan, Guo-Li Shen, Ru-Qin Yu
Biosensors and Bioelectronics 2013 Volume 41() pp:442-445
Publication Date(Web):15 March 2013
DOI:10.1016/j.bios.2012.09.013
A universal sensing platform for fluorescence turn-on detection of biomolecules is developed based on Fenton reaction triggered molecular beacon cleavage. Due to its high quenching efficiency, molecular beacons (MBs)-based sensing systems usually show low background fluorescence and large signal-to-background ratio. Glucose is chosen as a model biomolecule for constructing an MB-based fluorescence sensing system. In the presence of glucose, the glucose oxidase will bind with it and catalyze the oxidation to generate H2O2, which is further decomposed to produce OH through the Fe2+-catalyzed Fenton reaction. Then, in-situ-generated OH can trigger the cleavage of the MB, and its fluorescence intensity will be dramatically increased because of the complete separation of the fluorophore from the quencher. By employing molecular beacon as both recognition and reporter probes to low background signal, the proposed biosensors showed high sensitivity to targets. It also exhibited high selectivity owing to the high specificity of the enzymatic oxidation, which make it valuable for the detection of target biomolecule in complex biological samples.Highlights► A universal sensing platform for fluorescence detection of biomolecules is developed. ► The proposed sensing system is based on a Fenton reaction triggered molecular beacon cleavage strategy. ► It shows a “turn-on” fluorescence response to target biomolecule with high sensitivity. ► It also exhibits high selectivity owing to the high specificity of the enzymatic oxidation.
Co-reporter:Ai-Li Luo, Yi-Jun Gong, Yuan Yuan, Jing Zhang, Cui-Cui Zhang, Xiao-Bing Zhang, Weihong Tan
Talanta 2013 Volume 117() pp:326-332
Publication Date(Web):15 December 2013
DOI:10.1016/j.talanta.2013.09.033
•A new thioether spirocyclic rhodamine B based fluorescence probe TR was developed for Hg2+ detection.•The proposed probe exhibited a pH-independent and utrasensitive response to Hg2+ with high selectivity.•The living cell imaging experiments further demonstrated its value in the practical applications in biological systems.Development of fluorescent probes for Hg2+ has become a hot topic in modern chemical research due to its high toxicity. In this paper, we for the first time report the synthesis and application of a thioether spirocyclic rhodamine B derivative (TR) as an efficient fluorescent probe for Hg2+. TR was synthesized using a simple procedure under mild condition. By employing a thioether spirocycle instead of classic spirolactam as recognition unit, our proposed probe TR is acidity-insensitive, and exhibits a pH-independent and ultrasensitive response to Hg2+. The probe works well within a wide pH range from 3.5 to 11.5, and exhibits a 350-fold fluorescence enhancement upon 0.5 equiv of Hg2+ triggered, with a detection limit of 2.5 nM estimated for Hg2+. In virtue of the strong thiophilic characteristic of Hg2+, the response of the probe to Hg2+ is instantaneous and highly selective, which make it favorable for cellular Hg2+ imaging applications. It has been preliminarily used for highly sensitive monitoring of Hg2+ level in living cells with satisfying resolution, demonstrating its value of the practical applications in biological systems.
Co-reporter:Ya-Ru Liu, Rong Hu, Tao Liu, Xiao-Bing Zhang, Weihong Tan, Guo-Li Shen, Ru-Qin Yu
Talanta 2013 Volume 107() pp:402-407
Publication Date(Web):30 March 2013
DOI:10.1016/j.talanta.2013.01.038
A new and facile strategy using double-stranded DNA-copper nanoparticles (dsDNA-Cu NPs) as fluorescence reporters for the highly sensitive and selective detection of l-histidine was demonstrated. In the dsDNA-Cu NPs-based sensing system, the fluorescence was quenched considerably upon the addition of l-histidine. Under the optimized experimental conditions, the probe exhibits excellent performance (e.g., a satisfactory detection limit of 5 μM and high specificity). Our in situ method requires no covalent attachment of DNA to a fluorophore, which could significantly reduce the cost and simplify the procedure for l-histidine detection. Moreover, the proposed sensing system could be applicable for the detection of target biomolecule in complex biological samples. These striking properties make it an attractive platform for the direct detection of l-histidine.Highlights► Double-stranded DNA-copper nanoparticles sensing system was proposed for l-histidine detection. ► The probe was based on l-histidine-induced fluorescence quenching. ► This probe is simple and cost-efficient in design and operation.
Co-reporter:Rong Hu, Ting Fu, Xiao-Bing Zhang, Rong-Mei Kong, Li-Ping Qiu, Ya-Ru Liu, Xiao-Tong Liang, Weihong Tan, Guo-Li Shen and Ru-Qin Yu
Chemical Communications 2012 vol. 48(Issue 76) pp:9507-9509
Publication Date(Web):03 Aug 2012
DOI:10.1039/C2CC34848A
A proximity-dependent surface hybridization strategy is employed for designing a “signal-on” electrochemical DNAzyme biosensor. By taking advantage of the high sensitivity of the PDSH strategy, and by realizing the enzymatic hydrolysis reaction in a homogenous system with a unimolecular design, the proposed biosensor shows a very high sensitivity to target molecules.
Co-reporter:Hong-Min Meng, Ting Fu, Xiao-Bing Zhang, Nan-Nan Wang, Weihong Tan, Guo-Li Shen, and Ru-Qin Yu
Analytical Chemistry 2012 Volume 84(Issue 5) pp:2124-2128
Publication Date(Web):February 12, 2012
DOI:10.1021/ac300005f
It is well-known that Zr4+ could selectively bind with two phosphate-functionalized molecules through a coordinate covalent interaction to form a sandwich-structured complex (−PO32––Zr4+–PO32–−). In this paper, we for the first time converted such interaction into fluorescence sensing systems for Zr4+ via a target-triggered DNA molecular beacon strategy. In the new designed sensing system, two phosphorylated and pyrene-labeled oligonucleotides were chosen as both recognition and reporter units, which will be linked by target Zr4+ to form a hairpin structure and bring the two labeled pyrene molecules into close proximity, resulting in a “turn-on” excimer fluorescence signal. Moreover, γ-cyclodextrin was introduced to afford an amplified fluorescence signal and, therefore, provided an improved sensitivity for the target Zr4+. This allows detection of Zr4+ with high sensitivity (limit of detection, LOD = 200 nM) and excellent selectivity. The proposed sensing system has also been used for detection of Zr4+ in river water samples with satisfactory result.
Co-reporter:Zhen Jin, De-Xun Xie, Xiao-Bing Zhang, Yi-Jun Gong, and Weihong Tan
Analytical Chemistry 2012 Volume 84(Issue 10) pp:4253
Publication Date(Web):April 24, 2012
DOI:10.1021/ac300676v
Several heavy metal ions (HMIs), such as Cd2+, Pb2+, and Hg2+, are highly toxic even at very low concentrations. Although a large number of fluoroionphores have been synthesized for HMIs, only a few of them show detection limits that are below the maximum contamination levels in drinking water (usually in the nM range), and few of them can simultaneously detect and remove HMIs. In this work, we report a new fluoroionphore-ionic liquid hybrid-based strategy to improve the performance of classic fluoroionphores via a synergistic extraction effect and realize simultaneous instrument-free detection and removal of HMIs. As a proof-of-concept, Hg2+ was chosen as a model HMI, and a rhodamine thiospirolactam was chosen as a model fluoroionphore to construct bifunctional fluoroionphore-ionic liquid hybrid 1. The new sensing system could provide obviously improved sensitivity by simply increasing the aqueous-to-ionic liquid phase volume ratio to 10:1, resulting in a detection limit of 800 pM for Hg2+, and afford extraction efficiencies larger than 99% for Hg2+. The novel strategy provides a general platform for highly sensitive detection and removal of various HMIs in aqueous samples and holds promise for environmental and biomedical applications.
Co-reporter:Yi-Jun Gong, Xiao-Bing Zhang, Cui-Cui Zhang, Ai-Li Luo, Ting Fu, Weihong Tan, Guo-Li Shen, and Ru-Qin Yu
Analytical Chemistry 2012 Volume 84(Issue 24) pp:10777
Publication Date(Web):November 21, 2012
DOI:10.1021/ac302762d
Fluorescence resonance energy transfer (FRET) strategy has been widely applied in designing ratiometric probes for bioimaging applications. Unfortunately, for FRET systems, sufficiently large spectral overlap is necessary between the donor emission and the acceptor absorption, which would limit the resolution of double-channel images. The through-bond energy transfer (TBET) system does not need spectral overlap between donor and acceptor and could afford large wavelength difference between the two emissions with improved imaging resolution and higher energy transfer efficiency than that of the classical FRET system. It seems to be more favorable for designing ratiometric probes for bioimaging applications. In this paper, we have designed and synthesized a coumarin–rhodamine (CR) TBET system and demonstrated that TBET is a convenient strategy to design an efficient ratiometric fluorescent bioimaging probe for metal ions. Such TBET strategy is also universal, since no spectral overlap between the donor and the acceptor is necessary, and many more dye pairs than that of FRET could be chosen for probe design. As a proof-of-concept, Hg2+ was chosen as a model metal ion. By combining TBET strategy with dual-switch design, the proposed sensing platform shows two well-separated emission peaks with a wavelength difference of 110 nm, high energy transfer efficiency, and a large signal-to-background ratio, which affords a high sensitivity for the probe with a detection limit of 7 nM for Hg2+. Moreover, by employing an Hg2+-promoted desulfurization reaction as recognition unit, the probe also shows a high selectivity to Hg2+. All these unique features make it particularly favorable for ratiometric Hg2+ sensing and bioimaging applications. It has been preliminarily used for a ratiometric image of Hg2+ in living cells and practical detection of Hg2+ in river water samples with satisfying results.
Co-reporter:Yi-Jun Gong, Xiao-Bing Zhang, Zhuo Chen, Yuan Yuan, Zhen Jin, Lei Mei, Jing Zhang, Weihong Tan, Guo-Li Shen and Ru-Qin Yu
Analyst 2012 vol. 137(Issue 4) pp:932-938
Publication Date(Web):19 Dec 2011
DOI:10.1039/C2AN15935J
This paper described the optimized design, synthesis and application of a novel rhodamine thiospirolactam derivative as an ‘off-on’ fluorescent probe for the detection of Hg2+ in aqueous samples. The ‘off-on’ fluorescence and color signal change of the probe is based on an Hg2+-triggered domino reaction which brings on the opened-ring form of the rhodamine spirolactam to regain the conjugated system of the rhodamine skeleton. In the well designed probe, the thiospirolactam serves as both Hg2+ binding unit and electron-defect carbon centre, a phenolic hydroxyl with very strong nucleophilicity after deprotonation is chosen as the attacking unit, and a benzene ring is introduced on the linker to afford steric effects, which benefits an efficient nucleophilic reaction, with a high sensitivity towards Hg2+. It exhibits a stable response for Hg2+ from 1.0 × 10−8 to 1.0 × 10−6 M, with a detection limit of 3.0 × 10−9 M. The response of the probe to Hg2+ is highly selective and pH-insensitive, with a fast response time. All these unique features make it particularly favorable for cellular Hg2+ imaging applications. It has been preliminarily used for highly sensitive monitoring of Hg2+ levels in living cells with satisfying resolution.
Co-reporter:Rong Hu, Xiao-Bing Zhang, Rong-Mei Kong, Xu-Hua Zhao, Jianhui Jiang and Weihong Tan
Journal of Materials Chemistry A 2011 vol. 21(Issue 41) pp:16323-16334
Publication Date(Web):25 Aug 2011
DOI:10.1039/C1JM12588E
Nanomaterials possess several useful properties, including large surface-to-volume ratio, high biocompatibility, facile surface modification and overall structural robustness. They also have unique optical, magnetic and electronic properties. Nucleic acids, whether designed or selected in vitro, play important roles in biological assays and clinical diagnostics. In addition to nucleic acid probe-based nucleotide complementarity, aptamers, which can bind with high affinity and specificity to a wide range of target molecules, comprise a new class of nucleic acids selected in vitro. The coupling of nucleic acids, including aptamers, with various nanomaterials provides special opportunities for developing novel biosensing systems with advanced and powerful functions. This review summarizes recent achievements in the design of nucleic acid-functionalized nanomaterials for bioimaging applications, especially carbon nanomaterials, gold nanoparticles, semiconductor nanoparticles, magnetic nanoparticles, and polyacrylamide nanoparticles. Because DNA is easier to synthesize and more stable than RNA, this review mainly focuses on the bioimaging applications of DNA-functionalized nanomaterials.
Co-reporter:Li-Min Lu, Hong-Bo Li, Fengli Qu, Xiao-Bing Zhang, Guo-Li Shen, Ru-Qin Yu
Biosensors and Bioelectronics 2011 Volume 26(Issue 8) pp:3500-3504
Publication Date(Web):15 April 2011
DOI:10.1016/j.bios.2011.01.033
A nonenzymatic electrochemical biosensor was developed for the detection of glucose based on an electrode modified with palladium nanoparticles (PdNPs)-functioned graphene (nafion–graphene). The palladium nanoparticle–graphene nanohybrids were synthesized using an in situ reduction process. Nafion–graphene was first assembled onto an electrode to chemically adsorb Pd2+. And Pd2+ was subsequently reduced by hydrazine hydrate to form PdNPs in situ. Such a PdNPs–graphene nanohybrids-based electrode shows a very high electrochemical activity for electrocatalytic oxidation of glucose in alkaline medium. The proposed biosensor can be applied to the quantification of glucose with a wide linear range covering from 10 μM to 5 mM (R = 0.998) with a low detection limit of 1 μM. The experiment results also showed that the sensor exhibits good reproducibility and long-term stability, as well as high selectivity with no interference from other potential competing species.
Co-reporter:Danqing Lu, Lei He, Yaya Wang, Mengyi Xiong, Miaomiao Hu, Hao Liang, Shuangyan Huan, Xiao-Bing Zhang, Weihong Tan
Talanta (15 May 2017) Volume 167() pp:550-556
Publication Date(Web):15 May 2017
DOI:10.1016/j.talanta.2017.02.064
Co-reporter:Huapei Chen, Sitao Xie, Hao Liang, Cuichen Wu, Liang Cui, Shuang-Yan Huan, Xiaobing Zhang
Talanta (1 March 2017) Volume 164() pp:662-667
Publication Date(Web):1 March 2017
DOI:10.1016/j.talanta.2016.11.001
Co-reporter:Hong-Wen Liu, Shuai Xu, Peng Wang, Xiao-Xiao Hu, Jing Zhang, Lin Yuan, Xiao-Bing Zhang and Weihong Tan
Chemical Communications 2016 - vol. 52(Issue 83) pp:NaN12333-12333
Publication Date(Web):2016/09/21
DOI:10.1039/C6CC05880A
A promising two-photon fluorescent probe MNAH for detecting 1O2 during the PDT process in mitochondria was proposed for the first time. MNAH was successfully applied for two-photon imaging of 1O2 in living cells and tissues during the PDT process with deep-tissue imaging depth. MNAH can be a powerful molecular tool for studying 1O2 generation in mitochondria during the PDT process.
Co-reporter:Cui-Cui Zhang;Yijun Gong;Yuan Yuan;Aili Luo;Weijun Zhang;Jing Zhang;Xiaobing Zhang;Weihong Tan
Analytical Methods (2009-Present) 2014 - vol. 6(Issue 2) pp:NaN614-614
Publication Date(Web):2013/12/19
DOI:10.1039/C3AY41484A
In this paper, by employing a rigid xanthene scaffold as a bridge, we for the first time report a cofacial bispyrene derivative DPH as an efficient ratiometric fluorescent excimer probe for hypochlorite (OCl−). The probe is comprised of a rigid xanthene scaffold and two parallel pyrenes, which are linked by an OCl−-sensitive dicarboxylic acid hydrazide group. The introduction of OCl−, however, will induce oxidation of the dicarboxylic acid hydrazide moiety into a diimide group, and the subsequent hydrolysis of the diimide, to give 1-pyrenecarboxylic acid which exhibits a monomer emission at about 380 nm, with its intensity increasing with the addition of increased concentration of OCl−. Meanwhile, the excimer emission intensity gradually decreases. Such a ratiometric fluorescent response of the probe affords a high sensitivity to OCl−, with a linear response concentration range of 1 to 300 μM, and a detection limit of 0.35 μM for OCl−. It also shows a high selectivity for OCl− with no interference observed from other common anions and small molecules. Moreover, it can also act as a colorimetric probe for OCl− due to the cyan-to-blue fluorescence color change. It has been preliminarily used for practical detection of OCl− in river water samples with satisfying results.
Co-reporter:Xiaoyan Zhu, Mengyi Xiong, Hong-wen Liu, Guo-jiang Mao, Liyi Zhou, Jing Zhang, Xiaoxiao Hu, Xiao-Bing Zhang and Weihong Tan
Chemical Communications 2016 - vol. 52(Issue 4) pp:NaN736-736
Publication Date(Web):2015/11/03
DOI:10.1039/C5CC08695G
A FRET-based two-photon fluorescent probe, P-Np-Rhod, which exhibited a fast and high selective ratiometric response to nitroxyl, was first proposed. P-Np-Rhod was successfully applied to two-photon dual-channel imaging of nitroxyl in living cells and tissues with less cross-talk between channels and satisfactory deep-tissue imaging depth.
Co-reporter:Mengyi Xiong, Huijie Zhu, Qiming Rong, Chan Yang, Liping Qiu, Xiao-Bing Zhang and Weihong Tan
Chemical Communications 2016 - vol. 52(Issue 25) pp:NaN4682-4682
Publication Date(Web):2016/03/01
DOI:10.1039/C6CC00192K
Cell-surface fluorescent probes are effective tools in cell biology and engineering. Here, we for the first time report a diacyllipid–aptamer conjugate-based fluorescent probe which could anchor on cell membrane for real-time tracking of potassium ions in the cell microenvironment.
Co-reporter:Yifan Lv, Ruizi Peng, Yu Zhou, Xiaobing Zhang and Weihong Tan
Chemical Communications 2016 - vol. 52(Issue 7) pp:NaN1415-1415
Publication Date(Web):2015/11/18
DOI:10.1039/C5CC06937H
A catalytic self-assembled DNA dendritic complex was herein reported and used for siRNA-based gene silencing. This kind of one-pot DNA dendrimer can be conveniently prepared as needed, and it was demonstrated to have better silencing efficiency and lower cytotoxicity than commercial cationic lipid transfection agents.
Co-reporter:Liang Gong, Zilong Zhao, Yi-Fan Lv, Shuang-Yan Huan, Ting Fu, Xiao-Bing Zhang, Guo-Li Shen and Ru-Qin Yu
Chemical Communications 2015 - vol. 51(Issue 6) pp:NaN995-995
Publication Date(Web):2014/10/14
DOI:10.1039/C4CC06855F
DNAzymes, screened through in vitro selection, have shown great promise as molecular tools in the design of biosensors and nanodevices. The catalytic activities of DNAzymes depend specifically on cofactors and show multiple enzymatic turnover properties, which make DNAzymes both versatile recognition elements and outstanding signal amplifiers. Combining nanomaterials with unique optical, magnetic and electronic properties, DNAzymes may yield novel fluorescent, colorimetric, surface-enhanced Raman scattering (SERS), electrochemical and chemiluminescent biosensors. Moreover, some DNAzymes have been utilized as functional components to perform arithmetic operations or as “walkers” to move along DNA tracks. DNAzymes can also function as promising therapeutics, when designed to complement target mRNAs or viral RNAs, and consequently lead to down-regulation of protein expression. This feature article focuses on the most significant achievements in using DNAzymes as recognition elements and signal amplifiers for biosensors, and highlights the applications of DNAzymes in logic gates, DNA walkers and nanotherapeutics.
Co-reporter:Ting Fu, Xu-Hua Zhao, Hua-Rong Bai, Zi-Long Zhao, Rong Hu, Rong-Mei Kong, Xiao-Bing Zhang, Weihong Tan and Ru-Qin Yu
Chemical Communications 2013 - vol. 49(Issue 59) pp:NaN6646-6646
Publication Date(Web):2013/06/05
DOI:10.1039/C3CC43054E
Taking advantage of the super-quenching effect of the cationic perylene derivative on adjacent fluorophores, we for the first time reported a DNAzyme–perylene complex-based strategy for constructing fluorescence catalytic biosensors with improved sensitivity.
Co-reporter:Yong-Xiang Wu, Jun-Bin Li, Li-Hui Liang, Dan-Qing Lu, Jing Zhang, Guo-Jiang Mao, Li-Yi Zhou, Xiao-Bing Zhang, Weihong Tan, Guo-Li Shen and Ru-Qin Yu
Chemical Communications 2014 - vol. 50(Issue 16) pp:NaN2042-2042
Publication Date(Web):2013/12/20
DOI:10.1039/C3CC48649D
The water-soluble CP was conjugated with a rhodamine spirolactam for the first time to develop a new FRET-based ratiometric fluorescence sensing platform (CP 1) for intracellular metal-ion probing. CP 1 exhibits excellent water-solubility with two well-resolved emission peaks, which benefit ratiometric intracellular imaging applications.
Co-reporter:Rong Hu, Ting Fu, Xiao-Bing Zhang, Rong-Mei Kong, Li-Ping Qiu, Ya-Ru Liu, Xiao-Tong Liang, Weihong Tan, Guo-Li Shen and Ru-Qin Yu
Chemical Communications 2012 - vol. 48(Issue 76) pp:NaN9509-9509
Publication Date(Web):2012/08/03
DOI:10.1039/C2CC34848A
A proximity-dependent surface hybridization strategy is employed for designing a “signal-on” electrochemical DNAzyme biosensor. By taking advantage of the high sensitivity of the PDSH strategy, and by realizing the enzymatic hydrolysis reaction in a homogenous system with a unimolecular design, the proposed biosensor shows a very high sensitivity to target molecules.
Co-reporter:Rong Hu, Xiao-Bing Zhang, Rong-Mei Kong, Xu-Hua Zhao, Jianhui Jiang and Weihong Tan
Journal of Materials Chemistry A 2011 - vol. 21(Issue 41) pp:NaN16334-16334
Publication Date(Web):2011/08/25
DOI:10.1039/C1JM12588E
Nanomaterials possess several useful properties, including large surface-to-volume ratio, high biocompatibility, facile surface modification and overall structural robustness. They also have unique optical, magnetic and electronic properties. Nucleic acids, whether designed or selected in vitro, play important roles in biological assays and clinical diagnostics. In addition to nucleic acid probe-based nucleotide complementarity, aptamers, which can bind with high affinity and specificity to a wide range of target molecules, comprise a new class of nucleic acids selected in vitro. The coupling of nucleic acids, including aptamers, with various nanomaterials provides special opportunities for developing novel biosensing systems with advanced and powerful functions. This review summarizes recent achievements in the design of nucleic acid-functionalized nanomaterials for bioimaging applications, especially carbon nanomaterials, gold nanoparticles, semiconductor nanoparticles, magnetic nanoparticles, and polyacrylamide nanoparticles. Because DNA is easier to synthesize and more stable than RNA, this review mainly focuses on the bioimaging applications of DNA-functionalized nanomaterials.
Co-reporter:Hong-Min Meng, Hui Liu, Hailan Kuai, Ruizi Peng, Liuting Mo and Xiao-Bing Zhang
Chemical Society Reviews 2016 - vol. 45(Issue 9) pp:NaN2602-2602
Publication Date(Web):2016/03/08
DOI:10.1039/C5CS00645G
The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson–Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for in vivo applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field.
Co-reporter:Yi-Jun Gong, Xiao-Bing Zhang, Guo-Jiang Mao, Li Su, Hong-Min Meng, Weihong Tan, Suling Feng and Guisheng Zhang
Chemical Science (2010-Present) 2016 - vol. 7(Issue 3) pp:NaN2285-2285
Publication Date(Web):2016/01/04
DOI:10.1039/C5SC04014K
Near-infrared (NIR) fluorescent probes are attractive molecular tools for bioimaging because of their low autofluorescence interference, deep tissue penetration, and minimal damage to sample. However, most previously reported NIR probes exhibit small Stokes shift, typically less than 30 nm, and low fluorescence quantum yield, strictly limited contrast and spatial resolution for bioimaging. Herein, by expanding the π-conjugated system of rhodamine B, while, at the same time, keeping its rigid and planar structure, we reported an efficient NIR dye, HN7, with large stokes shift of 73 nm and fluorescence quantum yield as high as 0.72 in ethanol, values superior to those of such traditional cyanine NIR dyes as Cy5. Using HN7, living cells, tissues and mice were imaged, and the results showed significantly enhanced contrast, improved spatial resolution, and satisfactory tissue imaging depth when compared to Cy5. Moreover, the nonfluorescent spirocyclic structure of rhodamine B is an inherent component of HN7; therefore, our strategy provided a universal platform for the design of efficient NIR turn-on bioimaging probes for various targets. As a proof-of-concept, two different NIR probes, HN7-N2 and HN7-S for NO and Hg2+, respectively, were designed, synthesized, and successfully applied for the imaging of NO and Hg2+ in living cells, tissues and mice, respectively, demonstrating the potential bioimaging applications of the new probes. In sum, this new type of dye may present new avenues for the development of efficient NIR fluorescent probes for contrast-enhanced imaging in biological applications.
Co-reporter:Guo-Jiang Mao, Xiao-Bing Zhang, Xue-Lin Shi, Hong-Wen Liu, Yong-Xiang Wu, Li-Yi Zhou, Weihong Tan and Ru-Qin Yu
Chemical Communications 2014 - vol. 50(Issue 43) pp:NaN5792-5792
Publication Date(Web):2014/04/01
DOI:10.1039/C4CC01440E
A novel coumarin-based fluorescent probe, P-CM, for quantitative detection of nitroxyl (HNO) was developed. P-CM exhibits a selective response to HNO over other biological reductants and was also applied for quantitative detection of HNO in bovine serum with satisfactory results.
Co-reporter:Liang Gong, Hailan Kuai, Songlei Ren, Xu-Hua Zhao, Shuang-Yan Huan, Xiao-Bing Zhang and Weihong Tan
Chemical Communications 2015 - vol. 51(Issue 60) pp:NaN12098-12098
Publication Date(Web):2015/06/18
DOI:10.1039/C5CC04442A
By employing DNAzyme as a recognition group and amplifier, and DNA-stabilized silver nanoclusters (DNA/AgNCs) as signal reporters, we reported for the first time a label-free catalytic and molecular beacon as an amplified biosensing platform for highly selective detection of cofactors such as Pb2+ and L-histidine.
Co-reporter:
Analytical Methods (2009-Present) 2013 - vol. 5(Issue 16) pp:
Publication Date(Web):
DOI:10.1039/C3AY40354H
Aggregation-induced emission (AIE) dyes show different emission mechanism from traditional dyes, which were found to be nonluminescent in the solution state and emissive in the aggregate state, and have been well employed to design turn-on fluorescent probes for various targets. In this paper, we report for the first time a tetraphenylethylene-based AIE probe 1 for Al3+, which employed two diethylenetriamine units as the recognition ligand for Al3+. In the presence of Al3+, a large fluorescence enhancement was achieved for probe 1, which together with the low background fluorescence of free probe 1 allow for high sensitivity for Al3+, with a dynamic range from 2.0 × 10−6 to 1.1 × 10−5 M observed, and a detection limit of 5 × 10−7 M for Al3+. The proposed probe shows high selectivity to Al3+. UV-vis absorption spectra experiments and dynamic light scattering measurements were performed to verify the AIE sensing mechanism of probe 1. Moreover, a 1:1 stoichiometry was estimated for the 1–Al3+ complex via fluorescence Job's method.
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