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Now showing items 17 - 32 of 50

  • Differential expression of genes of Xylella fastidiosa in xylem fluid of citrus and grapevine

    Xiangyang Shi   Jianlong Bi   Joseph G. Morse   Nick C. Toscano   Donald A. Cooksey  

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  • Hyperpolarisability of (donor) 2-acceptor-type molecules determined by EFISHG

    Maltey, I.   Delaire, J.A.   Nakatani, K.   Pengfei Wang   Xiangyang Shi   Shikang Wu  

    Molecular first-order hyperpolarisabilities beta of (donor) 2-acceptor type molecules have been determined by electric field induced second-harmonic generation (EFISHG) experiments at 1.06 mum. The hyperpolarisability values are enhanced in these two dimensional charge transfer molecules, compared with a reference linear model molecule. One of these molecules absorbs part of the second-harmonic beam. We propose a determination method for beta that takes into account this phenomenon. Crystals of the title molecules exhibit second harmonic generation by the powder test
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  • Electrophoretic mobility and molecular distribution studies of poly(amidoamine) dendrimers of defined charges

    Xiangyang Shi   István Bányai   Keyla Rodriguez   Mohammad T. Islam   Wojciech Lesniak   Peter Balogh   Lajos P. Balogh   James R. Baker Jr.  

    Generation 5 ethylenediamine (EDA)-cored poly(amidoamine) (PAMAM) dendrimers (E5, E denotes the EDA core and 5 the generation number) with different degrees of acetylation and carboxylation were synthesized and used as a model system to investigate the effect of charge and the influence of dendrimer surface modifications on electrophoretic mobility (EM) and molecular distribution. The surface-modified dendrimers were characterized by size-exclusion chromatography, 1H NMR, MALDI-TOF-MS, PAGE, and CE. The focus of our study was to determine how EM changes as a function of particle charge and molecular mass, and how the molecular distribution changes due to surface modifications. We demonstrate that partially modified dendrimers have much broader migration peaks than those of fully surface functionalized or unmodified E5 dendrimers due to variations in the substitution of individual dendrimer surfaces. EM decreased nonlinearly with increases in surface acetylation for both PAMAM acetamides and PAMAM succinamic acids, indicating a complex migration activity in CE separations that is not solely due to charge/mass ratio changes. These studies provide new insights into dendrimer properties under an electric field, as well as into the characterization of dendrimer-based materials being developed for medical applications.
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  • RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells

    Xuedan He   Carla S. Alves   Nilsa Oliveira   João Rodrigues   Jingyi Zhu   István Bányai   Helena Tomás   Xiangyang Shi  

    Graphical abstract Highlights • G5 dendrimers can be modified with RGD peptide via a PEG spacer. • DOX can be encapsulated within G5.NHAc-FI-PEG-RGD dendrimers to form stable complexes. • G5.NHAc-FI-PEG-RGD/DOX complexes display a pH-responsive release behavior. • G5.NHAc-FI-PEG-RGD/DOX complexes exhibit non-compromised therapeutic efficacy. • G5.NHAc-FI-PEG-RGD/DOX complexes specifically inhibit α v β 3 integrin-overexpressing cancer cells. Abstract Development of multifunctional nanoscale drug-delivery systems for targeted cancer therapy still remains a great challenge. Here, we report the synthesis of cyclic arginine-glycine-aspartic acid (RGD) peptide-conjugated generation 5 (G5) poly(amidoamine) dendrimers for anticancer drug encapsulation and targeted therapy of cancer cells overexpressing α v β 3 integrins. In this study, amine-terminated G5 dendrimers were used as a platform to be sequentially modified with fluorescein isothiocyanate (FI) via a thiourea linkage and RGD peptide via a polyethylene glycol (PEG) spacer, followed by acetylation of the remaining dendrimer terminal amines. The developed multifunctional dendrimer platform (G5.NHAc-FI-PEG-RGD) was then used to encapsulate an anticancer drug doxorubicin (DOX). We show that approximately six DOX molecules are able to be encapsulated within each dendrimer platform. The formed complexes are water-soluble, stable, and able to release DOX in a sustained manner. One- and two-dimensional NMR techniques were applied to investigate the interaction between dendrimers and DOX, and the impact of the environmental pH on the release rate of DOX from the dendrimer/DOX complexes was also explored. Furthermore, cell biological studies demonstrate that the encapsulation of DOX within the G5.NHAc-FI-PEG-RGD dendrimers does not compromise the anticancer activity of DOX and that the therapeutic efficacy of the dendrimer/DOX complexes is solely related to the encapsulated DOX drug. Importantly, thanks to the role played by RGD-mediated targeting, the developed dendrimer/drug complexes are able to specifically target α v β 3 integrin-overexpressing cancer cells and display specific therapeutic efficacy to the target cells. The developed RGD peptide-targeted multifunctional dendrimers may thus be used as a versatile platform for targeted therapy of different types of α v β 3 integrin-overexpressing cancer cells.
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  • The aggregation and phase separation behavior of a hydrophobically modified poly(N-isopropylacrylamide)

    Xiangyang Shi   Junbai Li   Caomin Sun   Shikang Wu  

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  • Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells

    Xiangyang Shi   Su He Wang   Inhan Lee   Mingwu Shen   James R. Baker Jr.  

    Abstract Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au0)51.2-G5.NHAc-FI-FA]) in terms of their specific internalization to FA receptor (FAR)-overexpressing cancer cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and [(Au0)51.2-G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the two different nanostructures reveals that the surface area and the FA moiety distribution from the center of the geometry are slightly different. This slight difference may not be recognized by the FARs on the cell membrane, consequently leading to similar internalization kinetics. This study underlines the fact that metal or inorganic NPs entrapped within dendrimers interact with cells in a similar way to that of dendrimers lacking host NPs. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 936–942, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
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  • Dendrimer-Functionalized Shell-crosslinked Iron Oxide Nanoparticles for In-Vivo Magnetic Resonance Imaging of Tumors

    Xiangyang Shi   Su He Wang   Scott D. Swanson   Song Ge   Zhengyi Cao   Mary E. Van Antwerp   Kevin J. Landmark   James R. Baker Jr  

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  • Antitumor efficacy of doxorubicin-loaded electrospun nano-hydroxyapatite-poly(lactic-co-glycolic acid) composite nanofibers

    Fuyin Zheng   Shige Wang   Mingwu Shen   Meifang Zhu   Xiangyang Shi  

    Electrospun composite nanofibrous scaffolds have attracted much interest for use as drug delivery vehicles in recent years. Herein, we attempted to first encapsulate the anticancer drug doxorubicin (DOX) using inorganic rod-like nano-hydroxyapatite (n-HA) as a carrier. Then, the DOX-loaded n-HA particles were mixed with poly(lactic-co-glycolic acid) (PLGA) solution to fabricate electrospun hybrid nanofibers. The formation of drug-n-HA complexes and the drug-loaded composite nanofibers were characterized using different techniques. In vitro DOX release behavior was examined using UV-vis spectroscopy under both neutral and acidic conditions. The anticancer activity of the drug-loaded composite nanofibers was evaluated via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) viability assay and phase contrast microscopic morphology observation of a model KB cancer cell line (a human epithelial carcinoma cell line). We show that DOX can be successfully loaded onto the surface of the n-HA and the formed composite fibers have a uniform and continuous fibrous morphology. Importantly, the loaded DOX shows a sustained release profile, and the released DOX from the nanofibers displays noncompromised antitumor activity towards the growth inhibition of KB cells. With the significantly reduced burst release profile and the improved mechanical durability of the composite nanofiber system compared with n-HA-free PLGA nanofibers, the designed organic-inorganic hybrid nanofibers could be used as a versatile drug delivery system for encapsulation and sustained release of different drugs with prolonged therapeutic efficacy for different biomedical applications.
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  • The aggregation behavior of collagen in aqueous solution and its property of stabilizing liposomes in vitro

    Xiangyang Shi   Wanyun Ma   Caomin Sun   Shikang Wu  

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  • Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated multifunctional dendrimer-entrapped gold nanoparticles

    Jingyi Zhu   Linfeng Zheng   Shihui Wen   Yueqin Tang   Mingwu Shen   Guixiang Zhang   Xiangyang Shi  

    Abstract Development of multifunctional theranostic nanoplatforms for targeted cancer imaging and therapy still remains a great challenge. Herein, we report the use of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) covalently linked with α-tocopheryl succinate (α-TOS) as a platform for targeted cancer computed tomography (CT) imaging and therapy. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH 2 ) conjugated with fluorescein isothiocyanate (FI), polyethylene glycol (PEG)-modified α-TOS, and PEGylated folic acid (FA) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines. The formed multifunctional Au DENPs were characterized via different techniques. We show that the Au DENPs conjugated with approximately 9.8 α-TOS molecules per dendrimer and with an Au core size of 3.3 nm are water-dispersible, and stable under different pH and temperature conditions and in different aqueous media. The FA modification onto the Au DENPs enables efficient targeting of the particles to cancer cells overexpressing FA receptors (FAR), and effective targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo . Likewise, the covalent conjugation of α-TOS does not compromise its therapeutic activity, instead significantly improves its water solubility. Importantly, thanks to the role of FA-directed targeting, the formed multifunctional Au DENPs are able to exert the specific therapeutic efficacy of α-TOS to the FAR-overexpressing cancer cells in vitro and the xenografted tumor model in vivo . The developed multifunctional Au DENPs may hold a great promise to be used as a unique theranostic nanoplatform for targeted CT imaging and therapy of different types of cancer.
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  • Analysis of poly(amidoamine)-succinamic acid dendrimers by slab-gel electrophoresis and capillary zone electrophoresis

    Xiangyang Shi   Anil K. Patri   Wojciech Lesniak   Mohammad T. Islam   Chunxin Zhang   James R. Baker Jr   Lajos P. Balogh  

    Ethylenediamine (EDA)-core poly(amidoamine) (PAMAM) succinamic acid dendrimers (Ex.SAH, where x refers to the generation) were synthesized and analyzed by polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), potentiometric acid-base titration, and capillary zone electrophoresis (CZE). Various generations (E1.SAH-E7.SAH) PAMAMs and a succinamic acid terminated core-shell tecto(dendrimer) (E5(E3.SAH)(n)) were first analyzed by PAGE. PAGE results show that the relative mobilities of generation 2 to generation 7 dendrimers decreased with the increasing number of generations. The molecular mass of a generation 5 core generation 3 shell tecto(dendrimer) (denoted as E5(E3.SAH)(n)) was determined to be between the Mw of E6.SAH and E7.SAH. CZE analysis allowed the evaluation of electrophoretic properties of given-generation dendrimers. The electrophoretic mobilities of individual generations PAMAM polyanions are similar, indicating that the separation mainly depends on their approximately identical charge/mass ratio. The E5(E3.SAH)(n) tectodendrimer had a lower electrophoretic mobility, which was consistent with its lower charge/mass ratio. The combination of PAGE and CZE analysis provides an alternative and effective way to characterize this group of PAMAM-succinamic acid dendrimers.
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  • Targeted tumor dual mode CT/MR imaging using multifunctional polyethylenimine-entrapped gold nanoparticles loaded with gadolinium

    Benqing Zhou   Zuogang Xiong   Peng Wang   Chen Peng   Mingwu Shen   Serge Mignani   Jean-Pierre Majoral   Xiangyang Shi  

    We report the construction and characterization of polyethylenimine (PEI)-entrapped gold nanoparticles (AuNPs) chelated with gadolinium (Gd) ions for targeted dual mode tumor CT/MR imaging in vivo. In this work, polyethylene glycol (PEG) monomethyl ether-modified PEI was sequentially modified with Gd chelator and folic acid (FA)-linked PEG (FA-PEG) was used as a template to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining PEI surface amines. The formed FA-targeted PEI-entrapped AuNPs loaded with Gd (FA-Gd-Au PENPs) were well characterized in terms of structure, composition, morphology, and size distribution. We show that the FA-Gd-Au PENPs with an Au core size of 3.0 nm are water dispersible, colloidally stable, and noncytotoxic in a given concentration range. Thanks to the coexistence of Au and Gd elements within one nanoparticulate system, the FA-Gd-Au PENPs display a better X-ray attenuation property than clinical iodinated contrast agent (e.g. Omnipaque) and reasonable r1 relaxivity (1.1 mM−1s−1). These properties allow the FA-targeted particles to be used as an efficient nanoprobe for dual mode CT/MR imaging of tumors with excellent FA-mediated targeting specificity. With the demonstrated organ biocompatibility, the designed FA-Gd-Au PENPs may hold a great promise to be used as a nanoprobe for CT/MR dual mode imaging of different FA receptor-overexpressing tumors.
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  • Electrospun laponite-doped poly(lactic-co-glycolic acid) nanofibers for osteogenic differentiation of human mesenchymal stem cells

    Shige Wang   Castro, R.   Xiao An   Chenlei Song   Yu Luo   Mingwu Shen   Tomas, H.   Meifang Zhu   Xiangyang Shi  

    We report the fabrication of uniform electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers incorporated with laponite (LAP) nanodisks, a synthetic clay material for osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, a solution mixture of LAP suspension and PLGA was electrospun to form composite PLGA-LAP nanofibers with different LAP doping levels. The PLGA-LAP composite nanofibers formed were systematically characterized via different techniques. We show that the incorporation of LAP nanodisks does not significantly change the uniform PLGA fiber morphology, instead significantly improves the mechanical durability of the nanofibers. Compared to LAP-free PLGA nanofibers, the surface hydrophilicity and protein adsorption capacity of the composite nanofibers slightly increase after doping with LAP, while the hemocompatibility of the fibers does not appreciably change. The cytocompatibility of the PLGA-LAP composite nanofibers was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of L929 mouse fibroblasts and porcine iliac artery endothelial cells cultured onto the surface of the nanofibers. The results reveal that the incorporated LAP is beneficial to promote the cell adhesion and proliferation to some extent likely due to the improved surface hydrophilicity and protein adsorption capability of the fibers. Finally, the PLGA-LAP composite nanofibers were used as scaffolds for osteogenic differentiation of hMSCs. We show that both PLGA and PLGA-LAP composite nanofibers are able to support the osteoblast differentiation of hMSCs in osteogenic medium. Most strikingly, the doped LAP within the PLGA nanofibers is able to induce the osteoblast differentiation of hMSCs in growth medium without any inducing factors. The fabricated smooth and uniform organic-inorganic hybrid LAP-doped PLGA nanofibers may find many applications in the field of tissue engineering.
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  • Multifunctional PEI-entrapped gold nanoparticles enable efficient delivery of therapeutic siRNA into glioblastoma cells

    Lingdan Kong   Jieru Qiu   Xiangyang Shi  

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  • Multifunctional polyethylenimine-based nanoplatform for targeted anti-cancer drug delivery to tumors in vivo

    Benqing Zhou   Lingzhou Zhao   Jinhua Zhao   Xiangyang Shi  

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  • Electrospun attapulgite-doped poly(lactic-<em>co</em>-glycolic acid) nanofibers for osteogenic differentiation of human mesenchymal stem cells

    Zhe Wang   Yili Zhao   Yu Luo   Shige Wang   Leqiang Zhang   Xiangyang Shi  

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