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ABSTRACT: Fluorescence imaging in vivo allows non-invasive tumor diagnostic thus permitting a direct monitoring of cancer therapies progresses. It is established herein that fluorescent gold nanoclusters are spontaneously biosynthesized by cancerous cell (i.e., HepG2, human hepatocarcinoma cell line; K562, leukemia cell line) incubated with micromolar chloroauric acid solutions, a biocompatible molecular Au(III) species. Gold nanoparticles form by Au(III) reduction inside cells cytoplasms and ultimately concentrate around their nucleoli, thus affording precise cell imaging. Importantly, this does not occur in non-cancerous cells, as evidenced with human embryo liver cells (L02) used as controls. This dichotomy is exploited for a new strategy for in vivo self-bio-imaging of tumors. Subcutaneous injections of millimolar chloroauric acid solution near xenograft tumors of the nude mouse model of hepatocellular carcinoma or chronic myeloid leukemia led to efficient biosynthesis of fluorescent gold nanoclusters without significant dissemination to the surrounding normal tissues, hence allowing specific fluorescent self-bio-marking of the tumors.
Scientific Reports 01/2013; 3:1157.
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ABSTRACT: High level of oxidative stress is involved in formation of incipient tumor and carcinomatous cells. Here in this contribution we have explored a facile strategy to assess the oxidative stress elicited by hydrogen peroxide (H(2)O(2)) in cells with amperometric current-time technique in vitro. An electrochemical biosensor exhibiting high sensitivity and selectivity to H(2)O(2) is fabricated by integration of graphene with gold nanoparticles and poly(toluidine blue O) films. The efflux of H(2)O(2) from several representative tumor cells and normal cells on exposure to ascorbic acid could be detected by using the graphene-based nanocomposite films. The results indicate that tumor cells release much more H(2)O(2) than do the normal cells. The novel sensor raises the possibility for clinical diagnostic application to evaluate the higher level of intracellular oxidative stress of tumor cells in comparison with normal cells.
Biosensors & bioelectronics 10/2012; · 5.43 Impact Factor
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ABSTRACT: Alkaline phosphatase (ALP) catalyzes the hydrolysis and transphosphorylation of a wide variety of phosphoric acid monoesters and plays an important role in clinical diagnosis. In this work, an ALP-responsive anodic electrochemiluminescence (ECL) system based on coreaction of CdSe nanoparticles (NPs) and triethylamine has been designed for facile detection of ALP. The substrate of ALP, i.e., phenyl phosphate salt, shows no effect on the ECL emission whereas its catalytic product of phenol may induce ECL inhibition. For the buffer containing phenyl phosphate, the ECL emission is found to decline in the presence of ALP with different incubation time. The mechanism investigations indicate that the deposition of the electropolymerized phenol products may compete with the electrophoretic-driven adsorption of CdSe NPs on glassy carbon electrode and induce the ECL inhibition, which can be demonstrated by scanning electron microscopy, energy dispersive spectrometry, and anodic stripping voltammetry. Therefore, an inhibition type strategy has been developed to sensitively detect ALP ranging from 0.5 to 6.4 nM (activity ca. 2-25 U/L), with a detection limit of 0.5 nM. The potential interference from the common proteins is negligible. The recovery of ALP in diluted serum samples ranges from 91 to 114%, implicating its potential applications in the complex biological matrixes.
Analytical Chemistry 07/2012; 84(16):6986-93. · 5.86 Impact Factor
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ABSTRACT: Drug safety for human body should be carefully studied for its potent clinical application. In this report, the neurotoxicity of anticancer drug daunorubicin (DNR) and the oleic acid-capped Fe3O4 nanoparticles (NPs) for rat brain was firstly explored by using the in vivo microdialysis. The results indicated that the anticancer drug DNR itself had the serious neurotoxicity for the rat brain. And this neurotoxicity was influenced through the concentration changes of amino acids. The concentration level of some excitatory amino acids (such as Glu) and some inhibiting amino acid (such as Gly) were considerably decreased while that of the excitatory amino acid Asp was remarkably increased. For the DNR conjugated with Fe3O4 NPs nanocomposites, the side effect of DNR was visibly cut down, and the time to cause the side neurotoxicity was apparently shortened. Thus, it is evident that compared with DNR alone, the DNR conjugated with Fe3O4 NPs nanocomposites have the better biocompatibility and bio-security for the relevant cancer treatment in vitro and in vivo. This raises the promising possibility of the application of these DNR conjugated with Fe3O4 NPs nanocomposites for the target cancer therapy.
Journal of Biomedical Nanotechnology 06/2012; 8(3):417-23. · 4.22 Impact Factor
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ABSTRACT: This work designs a new strategy for the direct synthesis of different zinc oxide (ZnO) nanostructures at low temperatures. Micelles of dodecylamine (DDA) assembled in an ethanol-water system have been explored as a template to direct the growth of the ZnO nanostructures. The key species for the formation of the ZnO nanostructures, OH(-), can be provided by the water-induced protonation of DDA. The pH of the reaction micro-environment can be regulated by changing the input amount of water and DDA. By controlling the reaction temperature and pH, various ZnO nanostructures, i.e. quantum dots with green or yellow-green emissions, have been prepared. The relationship of the optical properties and the synthetic conditions has been further discussed. This strategy realizes the convenient preparation of ZnO QDs, indicating the potential prospects in the nanotechnology field for their low-cost synthesis. Meanwhile, the cellular toxicity study of ZnO nanoparticles toward cancer cells, including leukemia K562 and K562/A02 cells as well as HepG2 cells, indicates a selective cytotoxic effect of ZnO QDs against a broad range of human cancer cell lines.
Nanoscale 04/2012; 4(11):3530-5. · 5.91 Impact Factor
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ABSTRACT: This work designs an enzyme-stimulated nanogel aggregation system for the naked-eye assays of α-amylase activity. The visible aggregation of the starch-stabilized CdTe nanogels may be accelerated by α-amylase through its efficient cleavage of glycosidic bonds in the starch network, which has been verified by the evidences from transmission electron microscopy and dynamic light scattering spectra. The required aggregation time, as validated by both the theoretical deduction and the experimental results, is inversely proportional to the enzymatic activity. Therefore a facile method has been proposed for the detection of enzyme activity, with an excellent linear range and a low detection limit. This nanogel-based protocol can be successfully applied in the fast and accurate assays of α-amylase activity in saliva samples with a satisfactory correlation with the standard protocol, suggesting its promising applications in the biomedical and clinical fields, especially in point-of-care testing.
The Analyst 04/2012; 137(11):2582-7. · 4.23 Impact Factor
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ABSTRACT: Graphene is a kind of atomic crystal with two-dimensional polycyclic aromatic hydrocarbons planes, which is of great concern in various fields. This paper reviews the latest development of graphene-based materials in biomedical research fields in the recent years, including in vitro and in vivo toxicity, drug loading, targeting controlled release, as well as photodynamic therapy. These researches validate that the graphene-based materials indicate promising prospects in the application to biomedicine.
Yao xue xue bao = Acta pharmaceutica Sinica 03/2012; 47(3):291-8.
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ABSTRACT: In this study, the new nanocomposites of beta-cyclodextrin (beta-CD) and multi-walled carbon nanotubes (MWNTs) have been prepared and deposited on the indium tin oxide (ITO) electrodes to form the beta-CD/MWNTs modified ITO electrodes. These novel modified electrodes exhibited the abilities to lower the electrooxidation potentials of NADH substantially (ca. 600 mV) in comparison with bare ITO electrodes. Furthermore, a linear response to NADH in the concentration range of 4.0 x 10(-6) to 3.2 x 10(-3) mol/L was observed, with a detection limit of 8.0 x 10(-7) mol/L. Such ability of the novel nanocomposites to promote the electron-transfer reaction of NADH suggests great promise for dehydrogenase-based amperometric biosensors.
Journal of Nanoscience and Nanotechnology 03/2012; 12(3):1994-9. · 1.56 Impact Factor
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Angewandte Chemie International Edition 12/2011; 50(49):11644-8. · 13.45 Impact Factor
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ABSTRACT: Nanoconjugates composed of drug molecules encapsulated in quantum dots (QDs) attract enormous attention due to their promising bioimaging and biomedical applications. Here, the anticancer efficiency of potential pharmacophore agents (o-carborane (Cb), o-carborane-C-carboxylic acid (Cbac1), and o-carborane-C(1)C(2)-dicarboxylic acid (Cbac2) coupling with cadmium telluride QDs capped with cysteamine (CA-CdTe QDs)) have been explored. Compared with free CA-CdTe QDs, the composites consisting of Cbac1/Cbac2 and safe-dosage QDs can greatly improve the inhibition efficiency toward SMMC-7721 hepatocellular carcinoma cells with the aid of our real-time cell bioelectronic sensing system and the MTT assay. The enhanced cytotoxicity correlates with increased intracellular reactive oxygen species generation and cell apoptosis. Confocal laser scanning fluorescent microscopy shows improved cellular uptake and drug distribution of the Cbac1/Cbac2-CdTe QDs nanoconjugates. This work raises the possibility that the carborane pharmacophore in combination with QDs or other anticancer drugs may be viable for efficient cancer diagnosis and chemotherapy.
Nanomedicine: nanotechnology, biology, and medicine 11/2011; 8(6):860-9. · 5.44 Impact Factor
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ABSTRACT: A self-assembly hybrid of gold nanoparticles on graphene modified electrodes for low-potential NADH detection has been achieved. We used the natural polymer chitosan (Chit) to assist the stabilization of graphene in aqueous solution, and immobilize the electronegative Au nanoparticles (NPs) through electrostatic attraction. The synergy of Au NPs with graphene for catalytic oxidation of NADH made the overpotential ca. 220 mV less positive than that on the bare electrode, and remarkably increased the oxidation current. The amperometric sensors based on such modified electrodes for detection of NADH exhibited a good linearity from 1.5 to 320 μM, and showed high sensitivity with a low detection limit of 1.2 μM (S/N = 3). It could also exclude common interfering electroactive compounds like ascorbic acid and possessed good reproducibility and operational stability. Such eminent performance of the Au-RGO/Chit film together with the ability of graphene to significantly enhance the electron transfer between enzymes and the electrode suggested its promise for constructing novel graphene based dehydrogenase biosensors.
The Analyst 07/2011; 136(13):2735-40. · 4.23 Impact Factor
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ABSTRACT: As one of the best biocompatible semiconductor nanomaterials, TiO(2) nanofibers can act as a good photosensitizer material and show potential application in the field of drug carriers and photodynamic therapy to cure diseases. Celastrol, one of the active components extracted from T. wilfordii Hook F., was widely used in traditional Chinese medicine for many diseases. In this study, the cytotoxicity of celastrol for HepG2 cancer cells was firstly explored. The results showed that celastrol could inhibit cancer cell proliferation in a time-dependent and dose-dependent manner, inducing apoptosis and cell cycle arrest at G2/M phase in HepG2 cells. After the TiO(2) nanofibers were introduced into the system of celastrol, the cooperation effect showed that the nanocomposites between TiO(2) nanofibers and celastrol could enhance the cytotoxicity of celastrol for HepG2 cells and cut down the drug consumption so as to reduce the side-effect of the related drug. Associated with the photodynamic effect, it is evident that TiO(2) nanofibers could readily facilitate the potential application of the active compounds from natural products like celastrol. Turning to the advantages of nanotechnology, the combination of nanomaterials with the related monomer active compounds of promising Chinese medicine could play an important role to explore the relevant mechanism of the drug cellular interaction and promote the potential application of TiO(2) nanofibers in the clinical treatment.
Nanoscale 06/2011; 3(8):3115-22. · 5.91 Impact Factor
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ABSTRACT: Herein, we have designed a special strategy for detection of the important neurotransmitter serotonin by coupling the electrodeposition of serotonin oxidative products with the adsorption-controlled anodic electrochemiluminescent dynamics of the CdSe-triethylamine system. The stable electrochemiluminescent emission is found to decline in the presence of serotonin. This uncommon inhibition is attributed to the gradual accumulation of the electropolymerized serotonin products, which decrease the adsorbance of CdSe nanoparticles on the glass carbon electrode, as demonstrated by the scanning electron microscopic images (SEM) and the stripping voltammetric identification. Based on the inhibition effect, a facile strategy has been developed to sensitively detect the serotonin ranging from 0.2-10 μM, with a detection limit of 0.1 μM. The interference from the common species including ascorbic acid and uric acid has been investigated. The recovery rates in the spiked serum samples range from 94-112%, thereby implicating its potential applications in the complex bioassays.
Chemistry - An Asian Journal 04/2011; 6(6):1533-8. · 4.50 Impact Factor
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ABSTRACT: The emergence of the multidrug resistance (MDR) phenomenon in tumor has rendered many currently available chemotherapeutic drugs ineffective. Although many strategies have been explored to overcome MDR, the results have been disappointing to the obstacle. The aim of this study was to investigate whether the new strategy of combining drug-loaded nanoparticles (Nps) and ultrasound (US) would show useful effects on the reversal of MDR in tumor. The MDR leukemia K562/A02 cells were treated with the daunorubicin (DNR)-loaded TiO2 Nps drug carrier and US exposure. We observed good biocompatibility of the therapeutic approach, and the fresh evidence from the electrochemical studies, MTT assays, and caspase-3 immunocytochemistry demonstrated that the strategy could significantly increase the uptake of DNR by drug-resistant leukemia cells, and enhance the sensitivity of the MDR cells to the chemotherapeutic agents after released in the cells. The resisting fold became obviously lower and the apoptosis was induced in the cells as well. It was therefore concluded that the strategy could have good reversal ability of MDR in tumor. These findings reveal that the reversal of MDR in tumor by US mediated drug-loaded Nps crossing cell membranes could represent promising approach in cancer therapy.
Journal of Nanoscience and Nanotechnology 03/2011; 11(3):1834-40. · 1.56 Impact Factor
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ABSTRACT: The multidrug resistance (MDR) in cancer is a major chemotherapy obstacle, rendering many currently available chemotherapeutic drugs ineffective. The aim of this study was to explore the new strategy to early diagnose the MDR by electrochemical sensor based on carbon nanotubes-drug supramolecular interaction. The carbon nanotubes modified glassy carbon electrodes (CNTs/GCE) were directly immersed into the cells suspension of the sensitive leukemia cells K562 and/or its MDR cells K562/A02 to detect the response of the electrochemical probe of daunorubicin (DNR) residues after incubated with cells for 1h. The fresh evidence from the electrochemical studies based on CNTs/GCE demonstrated that the homogeneous, label-free strategy could directly measure the function of cell membrane transporters in MDR cancer cells, identify the cell phenotype (sensitive or MDR). When the different ratios of the sensitive leukemia cells K562 and its MDR ones K562/A02 were applied as a model of MDR levels to simulate the MDR occurrence in cancer, the cathodic peak current showed good linear response to the fraction of MDR with a correlation coefficient of 0.995. Therefore, the MDR fraction can be easily predicted based on the calibration curve of the cathodic peak current versus the fraction of MDR. These results indicated that the sensing strategy could provide a powerful tool for assessment of MDR in cancer. The new electrochemical sensor based on carbon nanotubes-drug supramolecular nanocomposites could represent promising approach in the rapid diagnosis of MDR in cancer.
Biosensors & bioelectronics 03/2011; 26(7):3361-6. · 5.43 Impact Factor
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ABSTRACT: Combinations of cancer therapy modalities are attracting attention to improve the outcome of treatment, since single modality has not always been sufficiently effective. The aim of this study was to investigate a new strategy of combined application of ZnO nanorods with anticancer drug daunorubicin (DNR) in photodynamic therapy (PDT). Using a simple one-step solid state reaction in air at room temperature, we were able to fabricate ZnO nanorods as the drug carrier of DNR in drug delivery system. The combination of ZnO nanorods with DNR induced the remarkable improvement in the anti-tumor activity, which has been demonstrated by the flow cytometry, MTT assay and nuclear DAPI staining. Furthermore, the possible signaling pathway was explored by immunocytochemistry. It was noted that the notable photodynamic activity of the non-cytotoxic ZnO nanorods could considerably increase cancer cell injury mediated by reactive oxygen species (ROS). For instance, in human hepatocarcinoma cells (SMMC-7721 cells), our observations demonstrated that ZnO nanorods could obviously increase the intracellular concentration of DNR and enhance its potential anti-tumor efficiency, indicating that ZnO nanorods could act as an efficient drug delivery carrier importing DNR into target cancer cells. Furthermore, photodynamic ZnO nanorods loaded chemotherapeutic agent could induce distinguished improvement in anti-tumor activity with UV illumination. These findings revealed that such modality combinations represent a promising approach in cancer therapy.
Biomaterials 03/2011; 32(7):1906-14. · 7.40 Impact Factor
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ABSTRACT: Recently, ZnO nanostructures with various morphologies have been synthesized with different structure directing agents. Among these works, little reports have been focused on the syntheses of the ZnO nanostructures at nearly neutral pH and relatively low temperature. This work explores a novel structure-directing agent, tris(hydroxymethyl)aminomethane (tris), for one-pot synthesis of hexagonal ZnO nanosheets at nearly neutral pH (i.e., 7.3) and low temperature (i.e., 80 degrees C). From the XRD and TEM results, the obtained ZnO nanosheets possess the perfect single crystalline structures. The tris molecule acts not only as the hydroxide anion generator, but also as the surface modification agent, as evidenced by the FT-IR spectrum. The yield of the products can be up to about 1.0 g per pot, indicating the industrial prospects for its large-scale and low-cost synthesis. The mechanism of nucleation and growth of the ZnO nanosheets has been proposed. The obtained ZnO nanosheets own the sharp strong fluorescence at 590 nm, which can be attributed to the defects on the surface of the ZnO nanostructures. In virtue of the fluorescent properties, the ZnO nanosheets have been successfully used for cell imaging, suggesting their promising clinic and biomedical applications.
Journal of Nanoscience and Nanotechnology 02/2011; 11(2):1117-22. · 1.56 Impact Factor
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ABSTRACT: In this contribution, we have prepared and explored a novel nano-interface based probe for the rapid identification and highly sensitive detection of cancer cells by means of an electrochemical study. The new probe tetrathiafulvalene (TTF) carboxylate salt (TTF-(COONBu(4))(2), ditetrabutylammonium salt for propylenedithio-4',5'-tetrathiafulvalene-4,5-dicarboxylate), which has specific spectral and electrochemical properties, has been synthesized and assembled with carbon nanotubes to form a new type of nanocomposite. A simple method of fabricating the β-CD/MWCNT modified electrodes based on functionalized multi-walled carbon nanotubes (MWCNTs) and β-cyclodextrin (β-CD) has been explored by using glassy carbon electrodes (GCEs), which could remarkably enhance the sensitivity of the biomolecular detection. Our results demonstrate that the combination of the new probe TTF-(COONBu(4))(2) with β-CD/MWCNT modified electrodes could be readily utilized to sensitively detect cancer cells such as liver cancer cells SMMC-7721 and HepG2, drug sensitive leukemia K562/B.W cells and drug resistant leukemia K562/ADM cells, with a detection limit of ~10(3) cells mL(-1). This may provide a novel strategy for the potential and promising application of the new TTF molecular probe in the development of multi-signal responsive biosensors for the early diagnosis of cancers.
The Analyst 11/2010; 135(11):2965-9. · 4.23 Impact Factor
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ABSTRACT: Strong alkaline microcavities were constructed through the water-induced protonation of dodecylamine for the synthesis of fluorescence-tunable ZnO QDs in neutral bulk reaction solution.
Chemical Communications 10/2010; 46(37):6900-2. · 6.17 Impact Factor
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ABSTRACT: Biointeractions between two organometallic compounds, a pair of ferrocene-substituted dithio-o-carborane isomers (C(14)H(20)B(10)FeS(2); denoted as FcSB1 and FcSB2), and myoglobin (Mb) have been investigated by means of electrochemistry, fluorescence, circular dichroism, and UV/Vis absorption spectroscopy. Our observations demonstrate that FcSB1 and FcSB2 could coordinate to the axial position trans to the histidine imidazole that induces the change of the heme iron from the high spin state to the low spin state and the changes of the conformation of the aromatic fluorophores of the selected heme protein. Such influences attribute to the structural features of FcSB1 and FcSB2 containing sulfur donor atoms and hydrophobic ferrocenyl and carboranyl units that leads to specific binding modalities with Mb. This study provides an insight into the understanding of relevant biointeractions between the new type of ferrocene-carborane conjugates and hemoproteins, and might shed light on the promising bioapplications of these multifunctional organometallic complexes.
Chemistry 08/2010; 16(29):8914-22. · 5.93 Impact Factor
