Lectin-conjugated Fe2O3@Au core@Shell nanoparticles as dual mode contrast agents for in vivo detection of tumor.

Here, we report the covalent conjugation of lectin on Fe2O3@Au core@shell nanoparticle (lectin-Fe2O3@Au NP) for T2-weighted magnetic resonance (MR) and X-ray computed tomography (CT) dual-modality imaging. The lectin-Fe2O3@Au NPs are prepared by coupling lectins to the Fe2O3@Au NP surfaces through bifunctional PEG NHS ester disulfide (NHS-PEG-S-S-PEG-NHS) linkers. After the nonspecific adsorption sites on the nanoparticle surface are blocked by thiolated PEG (PEG-SH), the lectin-Fe2O3@Au NPs exhibit excellent stability in biological medium and inappreciable cytotoxicity. A series of in vitro and in vivo experiments were then carried out for evaluating the capabilities of three selected lectin (ConA, RCA and WGA)-Fe2O3@Au NPs. The results revealed that the lectin-Fe2O3@Au NPs had a capacity not only for dual mode MR and CT imaging in vitro but also for MR and CT imaging of colorectal cancer in vivo. The experimental results also suggest that lectin could be used as tumor targeting ligand for synthesizing nanoparticle-based contrast agents.

Dispersive solid-phase extraction combined with dispersive liquid-liquid microextraction for the determination of polybrominated diphenyl ethers in plastic bottled beverage by GC-MS.

A simple, inexpensive and reliable analytical method was developed for the determination of polybrominated diphenyl ethers (PBDEs) in polyethylene terephthalate (PET) bottled beverage using GC-MS. The sample pretreatment using dispersive solid-phase extraction (DSPE) for removing matrix and dispersive liquid-liquid microextraction (DLLME) for enriching analytes was performed. For the DSPE, different sorbents such as primary amine, secondary amine, C(18) and graphitized carbon black were tested for different sample matrices. By means of DSPE, 60-89% of the sample matrices could be removed. Acetonitrile solution obtained by DSPE cleanup was directly used as the dispersant for the subsequent DLLME, which made the combination of the DSPE with the DLLME much more straightforward. Under the optimal conditions, the enrichment factors (EFs) of PBDEs ranged from 199 to 292. Using matrix-matched calibration, correlation coefficients above 0.994 were found and LODs ranged from 0.0023 to 0.15 µg/L. The recoveries were between 80 and 117% for beverages spiked at three different concentrations (1.0, 5.0 and 10 µg/L) with RSDs ranging from 3.7 to 14.7% (n=5). The results indicated that the combination of DSPE with DLLME was a powerful sample preparation tool for analysis of ultratrace analytes in complicated matrices.

Functional gold nanoparticles for studying the interaction of lectin with glycosyl complex on living cellular surfaces.

In this study, lectin-conjugated gold nanoparticles (GNPs) were prepared by standard biotin-streptavidin chemistry. The lectin-conjugated GNPs can be used as an indicator for studying the interaction of lectin with glycosyl complex on living cellular surfaces due to the high affinity of the lectin with saccharides. The interactions of two well-known lectins (Ricinus communis agglutinin and concanavalin A) and three different cell lines (HeLa, 293, and 293T) were selected here to establish this assay. Highly binding affinity of R. communis agglutinin with cells was demonstrated by conventional microscopic and UV-visible spectroscopic studies. In addition, the binding process can be inhibited by galactose, giving further proof of the binding mechanism.

Arsenic speciation in environmental waters by a new specific phosphine modified polymer microsphere preconcentration and HPLC-ICP-MS determination.

A new specific phosphine modified polymer microsphere (PPMs) was designed and used as the core adsorbent to comprehensively enrich both inorganic and organic arsenic species in environmental waters by on line solid-phase extraction (SPE). Avoiding any redox reagent, all the four arsenic species have been quantitatively retained on the home made mini-column with large number of positively charged adsorption groups, and then eluted rapidly (within seconds) with a mixed solution of ammonium nitrate and ammonium dihydrogen phosphate. The trace separation and determination of As(III), DMA, MMA and As(V) species have been simultaneously achieved by high performance liquid chromatography hyphenated to inductively coupled plasma spectrometry (HPLC-ICP-MS) technique. This work has developed a versatile tri-n-butylphosphine functionalized polymer microsphere for an efficient and reliable on-line of simultaneous preconcentration and detection of inorganic and organic arsenic speciation. Under the optimized experimental conditions, the enrichment factors obtained for As(III) and DMA with 25mL sample solution were 28, while for MMA and As(V) reached 30. The low detection limits of 1.2ngL(-1), 0.96ngL(-1), 0.82ngL(-1) and 0.91ngL(-1), with the relative standard deviations (RSDs) of 3.9%, 5.6%, 3.2% and 4.5% were obtained for As(III), DMA, MMA and As(V), respectively. The developed method was validated by analyzing Certified Reference Materials GSBZ 07-3171-2014, promising for routine monitoring of arsenic species in lake water, river water and seawater samples.

Method of labeling antibodies with europium(III)-4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-di-carboxylic acid chelate.

On the basis of Eu(III)-4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-di-carboxylic acid chelate (BCPDA) that was synthesized and characterized for time-resolved fluoroimmunoassay (TRFIA), Donkey anti-hepatitis B surface (anti-HBs) was labeled with BCPDA-Eu3+. Coomassie Brilliant Blue was used to determine the protein concentration and radio immunoassay (RIA) for detecting the biological activity in the labeled protein. Optimal conditions for the protein labeling were obtained by monitoring the reaction. Results suggested that the protein could be labeled with BCPDA under relatively moderate conditions. As a practical application, a protein-BCPDA-Eu3+ chelate was obtained by using BCPDA-protein that reacted with EuCl3 under certain conditions. Some properties of BCPDA and protein-BCPDA-Eu3+, such as absorption spectrum, emission spectrum and fluorescence lifetime, were discussed. The detection limit and the linear working range of the established method were also investigated.

Poly(ornithine-co-arginine-co-glycine-co-aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor-Penetrating Agent.

A novel random copolypeptide of ornithine, arginine, glycine, and aspartic acid [Poly(ornithine-co-arginine-co-glycine-co-aspartic acid), Poly(O,R,G,D)] has been prepared through ring-opening polymerization of N-δ-carbobenzoxy-l-ornithine N-carboxyanhydride [Orn(Cbz)-NCA)], l-glycine N-carboxyanhydride (Gly-NCA) and ß-benzyl l-aspartate N-carboxyanhydride [Asp(Bn)-NCA], following by subsequent deprotection and guanidization. The structure of Poly(O,R,G,D) was confirmed by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Low cytotoxicity of Poly(O,R,G,D) was confirmed from MTT assay. The Poly(O,R,G,D) contain some internal sequences of RXXR (X = O, R, G, or D) that could be proteolytically cleaved to expose the cryptic CendR element and bind to Neuropilin-1. This would lead to vascular and tissue permeabilization. Therefore trypsin-cleaved Poly(O,R,G,D) increase the vascular leakage of Evans blue from dermal microvessels at the injection site in vivo skin permeability assay. The intratumoral injection of the Poly(O,R,G,D) significantly enhanced the concentration of cisplatin-loaded nanoparticles in MCF-7 solid tumors. These results show that Poly(O,R,G,D) could increase the vascular leakage and tissue penetration of nanoparticles in a solid tumor and can be used as a potential polymeric tumor-penetrating agent.

Cyanex 923 as the extractant in a rare earth element impurity analysis of high-purity cerium oxide.

In this work, the feasibility of employing Cyanex 923 as an extractant into the non-cerium REE (rare earth elements) impurity analysis of high-purity cerium oxide was investigated. Through investigations on the choice of the extraction medium, the optimium extraction acidity, matrix Ce4+ effect on the non-cerium REE ion extraction, the optimium extractant concentration and suitable extracting time, and oscillation strengh, it was found that when the phase ratio was at 1:1 and the acicidity was about 2% H2SO4, by gently shaking by hand for about 2 min, 10 mL of 30% Cyanex 923 could not extract even for a 20 ng amount of non-cerium REE3+ ions. However, the extraction efficiency for Ce4+ of 100 mg total amount under the same conditions was about 96%, indicating that a 25-fold preconcentration factor could be achieved. Thus, it was concluded that Cyanex 923 could be used in a REE impurity analysis of 99.9999% or so pure cerium oxide for primary sepapation to elimilate matrix-induced interferences encountered in an ICP-MS (inductively coupled plasma mass spectroscopy) determination.

New insights into Alzheimer's disease amyloid inhibition: nanosized metallo-supramolecular complexes suppress aß-induced biosynthesis of heme and iron uptake in PC12 cells.

Nanosized metallo-supramolecular compounds, [Ni2 L3 ](4+) and [Fe2 L3 ](4+) , can not only strongly inhibit Aß aggregation but also reduce the peroxidase activity of Aß-heme. Further studies demonstrate that through blocking the heme-binding site, these two compounds can suppress Aß-induced biosynthesis of heme and iron uptake in PC12 cells. This work provides new insights into molecular mechanisms of Aß inhibitors on Aß-mediated neurotoxicity.

Transition-metal-substituted polyoxometalate derivatives as functional anti-amyloid agents for Alzheimer's disease.

Inhibitions of amyloid ß (Aß) aggregation and Aß-haem peroxidase-like activity have received much attention because these two symptoms can be the primary targets of therapeutic strategies for Alzheimer's disease (AD). Recently, our group found that polyoxometalate (POM) with a Wells-Dawson structure can efficiently inhibit Aß aggregation. However, the interaction between POMs and Aß is robust, but still needs to improve Aß binding affinity. More importantly, it is unclear whether POMs can cross the blood-brain barrier and decrease Aß-haem peroxidase-like activity. Here we show that our designed series of transition metal-functionalized POM derivatives with a defined histidine-chelated binding site have much better Aß inhibition and peroxidase-like activity inhibition effects than the parent POM. More intriguingly, we show that these compounds can cross the blood-brain barrier and are metabolized after 48 h. Our work provides insights into the design, synthesis and screening of inorganic metal compounds as multifunctional therapeutic agents against AD.

Preparation of porous polymer monolithic column incorporated with graphene nanosheets for solid phase microextraction and enrichment of glucocorticoids.

Novel monolithic capillary columns with embedded graphene were developed and used for polymer monolith microextraction (PMME) coupled to LC-MS analysis. The column was prepared inside fused silica capillaries (320 µm, i.d.) using thermally initiated free-radical polymerization with butyl methacrylate (BMA) as monomer, ethylene dimethacrylate (EDMA) as cross-linker, and 1,4-butanediol and 1-propanol as porogens. Graphene (GN) was incorporated into the poly(BMA-EDMA) monolith to enhance the loading capacity. The obtained GN and the poly(BMA-EDMA-GN) monolith were characterized by transmission electron microscope (TEM), atomic force microscopic (AFM) and scanning electron microscopy (SEM). The extraction performance of the monolithic column was evaluated by glucocorticoids (GCs) as the analytes. The operation parameters of PMME including desorption solvent, sample flow rate, sample volume, sample pH, and eluent flow rate were studied and optimized. When compared to the parent poly(BMA-EDMA) column and direct sample analysis, high enrichment capacity was observed in the case of GN-entrapped monolith. The GN incorporated monolithic capillary showed satisfactory reusability and stability during extraction. The limits of detection (S/N=3) for nine GCs were in the range of 0.13-1.93 ng/mL. Relative standard deviations for the determination of the target GCs were less than 14.5%. Finally, the PMME method, based on the developed monolithic capillary as the extraction media, was successfully applied to the determination of nine GCs in cosmetics. The recoveries of GCs spiked in different matrices ranged from 83.7% to 103.8%.

Methoxypoly(ethylene glycol)-block-poly(L-glutamic acid)-loaded cisplatin and a combination with iRGD for the treatment of non-small-cell lung cancers.

CDDP is loaded into methoxypoly(ethylene glycol)-block-poly(L-glutamic acid) (mPEG-b-PLG), and a combination with iRGD is applied for NSCLC chemotherapy. The CDDP-loaded micelles show sustained cisplatin release in PBS, dose- and time-dependent inhibition to HeLa and A549 cell proliferation, and no apparent hemolysis activities. In in vivo studies using subcutaneous NSCLC xenograft models (A549), both free CDDP and CDDP-loaded micelles show an evident anti-tumor effect. However, the toxicity of CDDP is significantly reduced in the cases of CDDP-loaded micelles and co-administration with iRGD, and the survival time is prolonged by over 30%. Therefore, mPEG-b-PLG-loaded cisplatin and the combination with iRGD provides a promising new therapy for NSCLC.

Fast speciation of mercury in seawater by short-column high-performance liquid chromatography hyphenated to inductively coupled plasma spectrometry after on-line cation exchange column preconcentration.

A simple and fast method for trace speciation analysis of mercury (Hg(2+)), methylmercury (MeHg(+)) and ethylmercury (EtHg(+)) in seawater has been developed by short-column high-performance liquid chromatography hyphenated to inductively coupled plasma spectrometry (HPLC-ICP-MS) after on-line cation-exchange column (CEC) preconcentration. The analytes were firstly adsorbed on the CEC without any extraneous reagent, and then were eluted rapidly (within seconds) and completely with a very low concentration of l-cysteine solution, which provides the conveniency for the on-line coupling of the preconcentration method and detection technique. To our best knowledge, it is for the first time to employ the CEC preconcentration technique to trap all of the three mercury species simultaneously at their positive charged status for the purpose of speciation analysis. Under the optimized conditions, a very high preconcentration factor up to 1250 has been obtained with 30mL sample solution, which leads to the very low detection limits of 0.042ngL(-1) for Hg(2+), 0.016ngL(-1) for MeHg(+) and 0.008ngL(-1) for EtHg(+) (as Hg), respectively. With the established method, three seawater samples were also analyzed, and all the three mercury species have been found in each sample, albeit at a very low concentration.

Biodegradable polymer - cisplatin(IV) conjugate as a pro-drug of cisplatin(II).

A Pt(IV) complex was covalently conjugated to a new biodegradable amphiphilic tri-block copolymer, MPEG-b-PCL-b-PLL, which contains pendant amino groups, to form a polymeric pro-drug of cisplatin(II), MPEG-b-PCL-b-PLL/Pt(IV). The conjugate was assembled into nano-micelles. The Pt(IV) complex, the polymer carrier and the conjugate were characterized systematically. In vitro release experiments showed that drug release from the polymer-Pt(IV) micelles follows an acid responsive and oxidation-reduction sensitive kinetics. HPLC-ICP-MS analysis revealed that cisplatin(II) can be released from the conjugate under an acidic plus a reductive condition which is available inside a cancerous cell. In vitro MTT assay demonstrated that the polymer-Pt(IV) micelles display higher cytotoxicity against SKOV-3 tumor cells than both cisplatin(II) and Pt(IV) complex. This enhanced cytotoxicity is attributed to effective internalization of the micelles by the cells via endocytosis mechanism, which was observed by fluorescence imaging and by direct determination of the platinum uptake by the cells. This polymer-Pt(IV) conjugate is a promising polymeric pro-drug of cisplatin in micellar form. It can protect the Pt(IV) complex against blood clearance. It can enter cancerous cells via endocytosis mechanism and then cisplatin(II) can be released. Therefore, this polymeric pro-drug of cisplatin is expected to find clinical applications in the future.

Influence of plant activity and phosphates on thorium bioavailability in soils from Baotou area, Inner Mongolia.

Harm of thorium to living organisms is governed by its bioavailability. Thorium bioavailability in the soil-plant system of Baotou rare earth industrial area was studied using pot experiments of wheat and single extraction methods. The effects of wheat growth stage and phosphate on thorium bioavailability were also investigated. Based on extractabilities of various extraction methods (CaCl(2), NH(4)NO(3), EDTA, HOAc) and correlation analysis of thorium uptake by wheat plant and extractable thorium, a mixture of 0.02M EDTA+0.5M NH(4)OAc (pH 4.6) was found suitable for evaluation of thorium bioavailability in Baotou soil, which could be predicted quantitatively by multiple regression models. Because of differences of wheat root activities, thorium bioavailability in rhizosphere soil was higher than in bulk soil at tillering stage, but the reverse occurred at jointing stage. Phosphate addition induced the mineralization of soluble thorium by forming stable thorium phosphate compounds, and reduced thorium bioavailability in soil.

[Adsorption behavior of exogenous thorium on soil contaminated by rare earth industries].

The adsorption behavior of exogenous thorium on soil was studied to evaluate the contaminated risk on soil. The adsorption capacity, equilibrium time, distribution coefficient and desorption ability were investigated by the experiments of static adsorption. The strong adsorption ability of exogenous thorium on soil samples was observed by high adsorption ratio (> 92%) and low desorption ratio (< 5%) in equilibrium, and the biggest distribution coefficient was over 10(4). The adsorption capacity and equilibrium time were related to soil properties. According to the results of adsorption, Freundlich equation (r > or = 0.9167) and Elovich equation (R2 > or = 0.8980) were primely fit for describing the thermodynamics and kinetics of the adsorption of exogenous thorium on soil samples, respectively, which indicated that the adsorption was belonged to the nonlinear adsorption, and was affected by the diffusion of thorium on soil surface and in mineral interbed. Sequential extraction procedure was employed to evaluate the bound fractions of exogenous thorium adsorbed on soil samples. Based on the extracted results of thorium fractions, exogenous thorium was presented in the labile nonresidual fractions (over 58%) at the low initial concentration (10(-7) - 10(-6) mol x L(-1)), and nonresidual fractions enhanced with the increase of the initial amount, meanwhile more exogenous throium was transferred to the stable residual fractions.

Evaluation of a sequential extraction for the speciation of thorium in soils from Baotou area, Inner Mongolia.

Sequential extraction procedures were widely applied for speciation of radioactive elements. In this study, the sequential extraction procedure developed by Martínez-Aguirre was employed for quantification of different chemical forms of thorium in the soil. The total amount of thorium in contaminated soil was much higher by four-fold than the local background value. The soil properties affect the amount of thorium and distribution of fractions in contaminated soil. Results showed that the proportion of thorium in soils from Baotou was found as the residual fraction (F5+F6)>absorbed fraction (F3), coprecipitated fraction (F4)>carbonates fraction (F2) and exchangeable fraction (F1) that could be available to plants. The recovery, calculated by ratio of the sum of the six fractions to the pseudo-total content of thorium, was in the range from 96% to 110%. A comparison was carried out between the sequential extraction and the single extraction to evaluate the selectivity of the extractants. It was found that the amount of thorium of absorbed fraction (F3) was higher in the single extraction than that estimated in the sequential extraction, possibly duo to transform of the labile form. While for non-residual fraction analysis, the single extraction scheme was a desirable alternative to the sequential extraction procedure. According to correlativity analysis of various fractions, it might be predicted that how the non-residual fractions of thorium were directionally transformed into interrelated fractions under the changes of conditions.

Preliminary results on the determination of ultratrace amounts of cadmium in tea samples using a flow injection on-line solid phase extraction separation and preconcentration technique to couple with a sequential injection hydride generation atomic fluorescence spectrometry.

In this work, a method was developed for determination of ultra-trace levels of Cd in tea samples by atomic fluorescence spectrometry (AFS). A flow injection solid phase extraction (FI-SPE) separation and preconcentration technique, to on-line couple with a sequential injection hydride generation (SI-HG) technique is employed in this study. Cd was preconcentrated on the SPE column, which was made from a neutral extractant named Cyanex 923, while other matrix ions or interfering ions were completely or mostly separated off. Conditions for the SPE separation and preconcentration, as well as conditions for the HG technique, were studied. Due to the separation of interfering elements, Cd hydride generation efficiency could be greatly enhanced with the sole presence of Co(2+) with a concentration of 200mugL(-1), which is much lower than those in other works previously reported. Interferences on both the Cd separation and preconcentration, and Cd hydride generation (HG) were investigated; it showed that both the separation and preconcentration system, and the HG system had a strong anti-interference ability. The SPE column could be repeatedly used at least 400 times, a R.S.D. of 0.97% was obtained for 6 measurements of Cd with 0.2mugL(-1) and a correlation coefficiency of 1.0000 was obtained for the measurement of a series of solutions with Cd concentrations from 0.1 to 2mugL(-1). The method has a low detection limit of 10.8ngL(-1) for a 25mL solution and was successfully validated by using two tea standard reference materials (GBW08513 and GBW07605).