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Sample records for diamsar conjugated rgd

  1. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    International Nuclear Information System (INIS)

    Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

    2014-01-01

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images

  2. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  3. Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

    Science.gov (United States)

    Kawamura, Wataru; Miura, Yutaka; Kokuryo, Daisuke; Toh, Kazuko; Yamada, Naoki; Nomoto, Takahiro; Matsumoto, Yu; Sueyoshi, Daiki; Liu, Xueying; Aoki, Ichio; Kano, Mitsunobu R; Nishiyama, Nobuhiro; Saga, Tsuneo; Kishimura, Akihiro; Kataoka, Kazunori

    2015-01-01

    Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by αVβ3 and αvβ5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress αVβ3 integrins. PMID:27877805

  4. RGD conjugated liposome-hollow silica hybrid nanovehicles for targeted and controlled delivery of arsenic trioxide against hepatic carcinoma.

    Science.gov (United States)

    Fei, Weidong; Zhang, Yan; Han, Shunping; Tao, Jiaoyang; Zheng, Hongyue; Wei, Yinghui; Zhu, Jiazhen; Li, Fanzhu; Wang, Xuanshen

    2017-03-15

    The aim of our study was to construct an Arg-Gly-Asp (RGD)-conjugated liposome-hollow silica hybrid nanovehicle for targeted delivery and controlled release of arsenic trioxide (ATO), whose anti-solid tumor effect was hampered by poor pharmacokinetics and dose-limited toxicity. Hydrophobic interactions were used to attach intact lipid membrane to the surface of chlorodimethyloctadecylsilane-modified hollow mesoporous silica nanoparticles. The prepared nanovehicles (RGD-LP-CHMSN) were characterized for uniform structure (silica core of ∼140nm in diameter and liposomal shell of ∼6nm), comparable drug loading efficiency (6.76%), desirable stability and strengthened controlled release. In vitro, RGD-LP-CHMSN showed good biocompatibility and low toxicity on HepG2, MCF-7 and LO2 cells. The targeted delivery of ATO by nanocarriers (RGD-LP-CHMSN-ATO) was demonstrated by an enhanced cellular uptake and a reduced half maximal inhibitory concentration (IC 50 ) value. In pharmacokinetic studies, the RGD-LP-CHMSN-ATO group, compared to the free ATO group, prolonged the half time (t 1/2β ) by 1.7 times and increased the area under curve (AUC) by 2.4 times. In addition, in a H22 tumor-xenograft mouse model, nanovehicles improved the targeting efficiency and anticancer potential of ATO. In conclusion, the strategy of constructing a nanocarrier with targeted delivery and controlled release characteristics is prospective to enhance the antitumor effect of ATO. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide-paclitaxel conjugate in mice with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Qizhen; Li, Zi-Bo; Chen, Kai; Wu, Zhanhong; He, Lina; Chen, Xiaoyuan [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Biophysics, and Bio-X Program, Stanford P095, CA (United States); Neamati, Nouri [University of Southern California, School of Pharmacy, Department of Pharmacology and Pharmaceutical Sciences, Los Angeles, CA (United States)

    2008-08-15

    Targeting drugs to receptors involved in tumor angiogenesis has been demonstrated as a novel and promising approach to improve cancer treatment. In this study, we evaluated the anti-tumor efficacy of a dimeric RGD peptide-paclitaxel conjugate (RGD2-PTX) in an orthotopic MDA-MB-435 breast cancer model. To assess the effect of conjugation and the presence of drug moiety on the MDA-MB-435 tumor and normal tissue uptake, the biodistribution of {sup 3}H-RGD2-PTX was compared with that of {sup 3}H-PTX. The treatment effect of RGD2-PTX and RGD2+PTX was measured by tumor size, {sup 18}F-FDG/PET, {sup 18}F-FLT/PET, and postmortem histopathology. By comparing the biodistribution of {sup 3}H-RGD2-PTX and {sup 3}H-PTX, we found that {sup 3}H-RGD2-PTX had higher initial tumor exposure dose and prolonged tumor retention than {sup 3}H-PTX. Metronomic low-dose treatment of breast cancer indicated that RGD2-PTX is significantly more effective than PTX+RGD2 combination and solvent control. Although in vivo {sup 18}F-FLT/PET imaging and ex vivo Ki67 staining indicated little effect of the PTX-based drug on cell proliferation, {sup 18}F-FDG/PET imaging showed significantly reduced tumor metabolism in the RGD2-PTX-treated mice versus those treated with RGD2+PTX and solvent control. Terminal uridine deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining also showed that RGD2-PTX treatment also had significantly higher cell apoptosis ratio than the other two groups. Moreover, the microvessel density was significantly reduced after RGD2-PTX treatment as determined by CD31 staining. Our results demonstrate that integrin-targeted delivery of paclitaxel allows preferential cytotoxicity to integrin-expressing tumor cells and tumor vasculature. The targeted delivery strategies developed in this study may also be applied to other chemotherapeutics for selective tumor killing. (orig.)

  6. Conjugation of cRGD Peptide to Chlorophyll-a Based Photosensitizer (HPPH) Alters its Pharmacokinetics with Enhanced Tumor-Imaging and Photosensitizing (PDT) Efficacy

    Science.gov (United States)

    Srivatsan, Avinash; Ethirajan, Manivannan; Pandey, Suresh K.; Dubey, Shipra; Zheng, Xiang; Liu, Ting-Hsiu; Shibata, Masayuki; Missert, Joseph; Morgan, Janet; Pandey, Ravindra K.

    2011-01-01

    The αvβ3 integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Cyclic Arg-Gly-Asp (cRGD) peptide represents a selective αvβ3 integrin ligand that has been extensively used for research, therapy, and diagnosis of neoangiogenesis. For developing photosensitizers with enhanced PDT efficacy, we here report the synthesis of a series of bifunctional agents in which the 3-(1′-hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH), a chlorophyll-based photosensitizer was conjugated to cRGD and the related analogs. The cell uptake, in vitro PDT efficacy of the conjugates were studied in αvβ3 integrin overexpressing U87 and 4T1 cell lines whereas the in vivo PDT efficacy and fluorescence-imaging potential of the conjugates were compared with the corresponding non-conjugated photosensitizer HPPH in 4T1 tumors. Compared to HPPH, the HPPH-cRGD conjugate in which the arginine and aspartic acid moieties were available for binding to two subunits of αvβ3 integrin showed faster clearance, enhanced tumor-imaging and PDT efficacy at 2–4 h post-injection. Molecular modeling studies also confirmed that the presence of HPPH moiety in HPPH-cRGD conjugate does not interfere with specific recognition of cRGD by αvβ3 integrin. Compared to U87 and 4T1 cells the HPPH-cRGD showed significantly low photosensitizing efficacy in A431 (αvβ3 negative) tumor cells, suggesting possible target-specificity of the conjugate. PMID:21702452

  7. NIR Emitting Nanoprobes Based on Cyclic RGD Motif Conjugated PbS Quantum Dots for Integrin-Targeted Optical Bioimaging.

    Science.gov (United States)

    Depalo, N; Corricelli, M; De Paola, I; Valente, G; Iacobazzi, R M; Altamura, E; Debellis, D; Comegna, D; Fanizza, E; Denora, N; Laquintana, V; Mavelli, F; Striccoli, M; Saviano, M; Agostiano, A; Del Gatto, A; Zaccaro, L; Curri, M L

    2017-12-13

    Here, silica-coated PbS quantum dots (QDs) with photoluminescence emission properties in the near-infrared (NIR) region are proposed as potential effective single particle optical nanoprobes for future in vivo imaging of tumors. The dispersibility in aqueous medium of hydrophobic PbS QDs was accomplished by growing a silica shell on their surface by exploiting a base assisted water-in-oil microemulsion method. The silica-coated PbS QDs were then conjugated with a specifically designed cyclic arginine-glycine-aspartic acid (cRGD) peptide that is able to specifically recognize αvβ3 integrins, which are overexpressed in angiogenic tumor-induced vasculatures and on some solid tumors, to achieve tumor-specific targeting. The cRGD peptide PbS silica-coated QDs were systematically characterized, at each step of their preparation, by means of complementary optical and structural techniques, demonstrating appropriate colloidal stability and the maintenance of their optical futures in aqueous solutions. The cellular uptake of cRGD peptide functionalized luminescent nanostructures in human melanoma cells, where overexpression of αvβ3 was observed, was assessed by means of confocal microscopy analysis and cytometric study. The selectivity of the cRGD peptide PbS silica-coated QDs for the αvβ3 integrin was established, consequently highlighting the significant potential of the developed NIR emitting nanostructures as optically traceable nanoprobes for future αvβ3 integrin receptor in vivo targeting in the NIR region.

  8. Conjugation of cRGD peptide to chlorophyll a based photosensitizer (HPPH) alters its pharmacokinetics with enhanced tumor-imaging and photosensitizing (PDT) efficacy.

    Science.gov (United States)

    Srivatsan, Avinash; Ethirajan, Manivannan; Pandey, Suresh K; Dubey, Shipra; Zheng, Xiang; Liu, Ting-Hsiu; Shibata, Masayuki; Missert, Joseph; Morgan, Janet; Pandey, Ravindra K

    2011-08-01

    The α(v)β(3) integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Cyclic Arg-Gly-Asp (cRGD) peptide represents a selective α(v)β(3) integrin ligand that has been extensively used for research, therapy, and diagnosis of neoangiogenesis. For developing photosensitizers with enhanced PDT efficacy, we here report the synthesis of a series of bifunctional agents in which the 3-(1'-hexyloxyethyl)-3-devinylpyropheophorbide a (HPPH), a chlorophyll-based photosensitizer, was conjugated to cRGD and the related analogues. The cell uptake and in vitro PDT efficacy of the conjugates were studied in α(v)β(3) integrin overexpressing U87 and 4T1 cell lines whereas the in vivo PDT efficacy and fluorescence-imaging potential of the conjugates were compared with the corresponding nonconjugated photosensitizer HPPH in 4T1 tumors. Compared to HPPH, the HPPH-cRGD conjugate in which the arginine and aspartic acid moieties were available for binding to two subunits of α(v)β(3) integrin showed faster clearance, enhanced tumor imaging and enhanced PDT efficacy at 2-4 h postinjection. Molecular modeling studies also confirmed that the presence of the HPPH moiety in HPPH-cRGD conjugate does not interfere with specific recognition of cRGD by α(v)β(3) integrin. Compared to U87 and 4T1 cells the HPPH-cRGD showed significantly low photosensitizing efficacy in A431 (α(v)β(3) negative) tumor cells, suggesting possible target specificity of the conjugate.

  9. Anti-EGFR-iRGD recombinant protein conjugated silk fibroin nanoparticles for enhanced tumor targeting and antitumor efficiency

    Directory of Open Access Journals (Sweden)

    Bian X

    2016-05-01

    Full Text Available Xinyu Bian,* Puyuan Wu,* Huizi Sha, Hanqing Qian, Qing Wang, Lei Cheng, Yang Yang, Mi Yang, Baorui LiuComprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workAbstract: In this study, we report a novel kind of targeting with paclitaxel (PTX-loaded silk fibroin nanoparticles conjugated with iRGD–EGFR nanobody recombinant protein (anti-EGFR-iRGD. The new nanoparticles (called A-PTX-SF-NPs were prepared using the carbodiimide-mediated coupling procedure and their characteristics were evaluated. The cellular cytotoxicity and cellular uptake of A-PTX-SF-NPs were also investigated. The results in vivo suggested that NPs conjugated with the recombinant protein exhibited more targeting and anti-neoplastic property in cells with high EGFR expression. In the in vivo antitumor efficacy assay, the A-PTX-SF-NPs group showed slower tumor growth and smaller tumor volumes than PTX-SF-NPs in a HeLa xenograft mouse model. A real-time near-infrared fluorescence imaging study showed that A-PTX-SF-NPs could target the tumor more effectively. These results suggest that the anticancer activity and tumor targeting of A-PTX-SF-NPs were superior to those of PTX-SF-NPs and may have the potential to be used for targeted delivery for tumor therapies. Keywords: EGFR, nanobody, iRGD, recombinant protein, targeting drug carriers, antitumor efficiency

  10. Improved Pharmacokinetics Following PEGylation and Dimerization of a c(RGD-ACH-K) Conjugate Used for Tumor Positron Emission Tomography Imaging.

    Science.gov (United States)

    Lee, Ji Woong; Lee, Yong Jin; Shin, Un Chol; Kim, Suhng Wook; Kim, Byung Il; Lee, Kyo Chul; Kim, Jung Young; Park, Ji-Ae

    2016-10-01

    Improving the in vivo pharmacokinetics (PK) of positron emission tomography (PET) radiotracers is of critical importance to tumor diagnosis and therapy. In the case of peptide-based radiotracers, the modification and addition of a linker or spacer functional group often offer faster in vivo pharmacokinetic behavior. In this study, the authors introduced two new PEGlyated dimeric c(RGD-ACH-K) conjugates, in which an aminocyclohexane carboxylic acid (ACH) is inserted into the ring chain of the cyclic RGD peptides, with a common bifunctional chelator (DOTA or NOTA) used for labeling with radiometals (including 68 Ga and 64 Cu). The addition of polyethylene glycol (PEG) and dimerization of c(RGD-ACH-K) affected the PK of the renal system and the tumor-targeting ability, relative to unmodified molecule. As a result, both 64 Cu-DOTA-E[c(RGD-ACH-K)] 2 (complex 1) and 64 Cu-NOTA-E[c(RGD-ACH-K)] 2 (complex 2) exhibited specific tumor-targeting properties relative to tumor-blocking control group, most likely resulting from improved in vivo tumor imaging. The in vivo tumor-to-blood ratio of the 64 Cu(NOTA) complex shows better PET imaging than that of the 64 Cu(DOTA) complex, which should lead to improved dosimetry and increased suitability for noninvasive monitoring of tumor growth or tumor-targeted radionuclide therapy.

  11. MicroPET/CT imaging of {alpha}{sub v}{beta}{sub 3} integrin via a novel {sup 68}Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Menichetti, Luca; Kusmic, Claudia; Panetta, Daniele; Petroni, Debora; Salvadori, Piero A. [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Arosio, Daniela; Manzoni, Leonardo [CNR-Institute of Molecular Science and Technologies (ISTM), Milan (Italy); Matteucci, Marco [Scuola Superiore Sant' Anna, Pisa (Italy); Casagrande, Cesare [University of Milan, Department of Chemistry, Milan (Italy); L' Abbate, Antonio [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Scuola Superiore Sant' Anna, Pisa (Italy)

    2013-08-15

    The {alpha}{sub v}{beta}{sub 3} integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel {sup 68}Ga-2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI. A straightforward labelling chemistry to attach the radionuclide {sup 68}Ga to a NOTA-based chelating agent conjugated with a cyclic RGD peptidomimetic is described. Affinity for {alpha}{sub v}{beta}{sub 3} integrin was assessed by in vitro receptor binding assay. The proof-of-concept in vivo studies combined the {sup 68}Ga-NOTA-RGD with the flow tracer {sup 13}N-NH{sub 3} imaging in order to obtain positron emission tomography (PET)/CT imaging of both integrin expression and perfusion defect at 4 weeks after infarction. Hearts were then processed for immunostaining of integrin {beta}{sub 3}. NOTA-RGD conjugate displayed a binding affinity for {alpha}{sub v}{beta}{sub 3} integrin of 27.9 {+-} 6.8 nM. {sup 68}Ga-NOTA-RGD showed stability without detectable degradation or formation of by-products in urine up to 2 h following injection in the rat. MI hearts exhibited {sup 68}Ga-NOTA-RGD uptake in correspondence to infarcted and border zone regions. The tracer signal drew a parallel with vascular remodelling due to ischaemia-induced angiogenesis as assessed by immunohistochemistry. As compared to similar imaging approaches using the {sup 18}F-galacto-derivative, we documented for the first time with microPET/CT imaging the {sup 68}Ga-NOTA-RGD derivative that appears eligible for PET imaging in animal models of vascular remodelling during evolving MI. The simple chemistry employed to

  12. cRGD-conjugated magnetic-fluorescent liposomes for targeted dual-modality imaging of bone metastasis from prostate cancer.

    Science.gov (United States)

    Wang, Fangfang; Chen, Zhongping; Zhu, Li

    2015-01-01

    We reported the development of multifunctional liposomes as a dual-modality probe to facilitate targeted magnetic resonance and fluorescent imaging of bone metastasis from advanced cancer. Multifunctional liposomes consisted of liposomes as a carrier, hydrophobic CdSe QDs in phospholipid bilayer, hydrophilic iron oxide nanoparticles in interior vesicle, lipid-PEG derivative on the surface and cRGDyk peptide conjugated to distal ends of lipid-PEG derivative. Excellent stability, effective detection signal, low toxicity, high resistance to phagocytosis by macrophages and good specificity to tumor of multifunctional liposomes were confirmed by in vitro characterization. The in vivo results demonstrated that multifunctional liposomes accumulated mainly in tumor and liver, indicating that targeted dual-modality imaging was achieved, and the results from two kinds of modalities were consistent and complementary. These findings provide a helpful strategy for detection of bone metastases in a more effective manner for initiation of appropriate therapy.

  13. Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Cui Y

    2016-11-01

    Full Text Available Yanfen Cui,1,* Caiyuan Zhang,1,* Ran Luo,1 Huanhuan Liu,1 Zhongyang Zhang,1 Tianyong Xu,2 Yong Zhang,2 Dengbin Wang11Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 2MR Advanced Application and Research Center, GE Healthcare China, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: Arginine-glycine-aspartic acid (RGD-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA-coated ultrasmall superparamagnetic iron oxide (USPIO (referred to as RGD-PAA-USPIO in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC xenograft model by magnetic resonance imaging (MRI.Materials and methods: The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group.Results: The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05.Conclusion: This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in

  14. Combined spectroscopic and molecular docking techniques to study interaction of Zn (II) DiAmsar with serum albumins

    Energy Technology Data Exchange (ETDEWEB)

    Bardajee, Ghasem Rezanejade, E-mail: rezanejad@pnu.ac.ir; Hooshyar, Zari; Shafagh, Pegah; Ghiasvand, Samira; Kakavand, Nahaleh

    2014-12-15

    Zinc (II) diamine-sarcophagine (Zn (II) DiAmsar) as a water soluble hexadentate ligand was synthesized and characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) and UV–visible (UV–vis) spectroscopy. The bindings of Zn (II) DiAmsar with human serum albumin (HSA) and bovine serum albumin (BSA) were investigated under the simulative physiological conditions. To study this binding, the fluorescence spectra in combination with FT-IR, UV–vis, cyclic voltammetry (CV), and molecular docking techniques were used in the present work. The results indicate that Zn (II) DiAmsar quenched effectively the intrinsic fluorescence of HSA and BSA via a static quenching process. The fluorescence quenching data was also used to determine binding sites and binding constants at different temperatures. The calculated thermodynamic parameters (∆G°, ∆H°, and ∆S°) suggest that the binding process occurs spontaneously by involving hydrogen bond and van der Waals interactions. The distance between HSA (or BSA) as a donor and Zn (II) DiAmsar as an acceptor was obtained according to fluorescence resonance energy transfer (FRET). In addition, the docking results revealed the possible binding sites and assess the microenvironment around the bounded Zn (II) DiAmsar.

  15. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  16. Galloyl-RGD as a new cosmetic ingredient

    Science.gov (United States)

    2014-01-01

    Background The cosmetics market has rapidly increased over the last years. For example, in 2011 it reached 242.8 billion US dollars, which was a 3.9% increase compared to 2010. There have been many recent trials aimed at finding the functional ingredients for new cosmetics. Gallic acid is a phytochemical derived from various herbs, and has anti-fungal, anti-viral, and antioxidant properties. Although phytochemicals are useful as cosmetic ingredients, they have a number of drawbacks, such as thermal stability, residence time in the skin, and permeability through the dermal layer. To overcome these problems, we considered conjugation of gallic acid with a peptide. Results We synthesized galloyl-RGD, which represents a conjugate of gallic acid and the peptide RGD, purified it by HPLC and characterized by MALDI-TOF with the aim of using it as a new cosmetic ingredient. Thermal stability of galloyl-RGD was tested at alternating temperatures (consecutive 4°C, 20°C, or 40°C for 8 h each) on days 2, 21, 41, and 61. Galloyl-RGD was relatively safe to HaCaT keratinocytes, as their viability after 48 h incubation with 500 ppm galloyl-RGD was 93.53%. In the group treated with 50 ppm galloyl-RGD, 85.0% of free radicals were removed, whereas 1000 ppm galloyl-RGD suppressed not only L-DOPA formation (43.8%) but also L-DOPA oxidation (54.4%). Conclusions Galloyl-RGD is a promising candidate for a cosmetic ingredient. PMID:25103826

  17. Comparison of biological properties of 111In-labeled dimeric cyclic RGD peptides

    International Nuclear Information System (INIS)

    Zheng, Yumin; Ji, Shundong; Tomaselli, Elena; Yang, Yong; Liu, Shuang

    2015-01-01

    Introduction: In this study two 111 In-labeled dimeric cyclic RGD peptides, 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ), were evaluated as radiotracers for breast tumor imaging. The objective was to evaluate the impact of SAA, PEG 2 and 1,2,3-triazole linkers as compare to PEG 4 on the tumor uptake and excretion kinetics of 111 In radiotracers. Methods: DOTA-Galacto-RGD 2 was prepared by conjugation of Galacto-RGD 2 with DOTA-OSu in the presence of diisopropylethylamine. Its integrin α v β 3 binding affinity was determined using a whole-cell displacement assay against 125 I-echistatin bound to U87MG glioma cells, and was compared with those of c(RGDfK), DOTA-3P-RGD 2 and DOTA-3P-RGK 2 (a nonsense peptide conjugate with “scrambled” RGK sequences). 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ) were prepared and evaluated for their tumor-targeting capability and biodistribution properties in athymic nude mice bearing MDA-MB-435 breast tumor xenografts. Planar imaging studies were performed to demonstrate the utility of 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ) for breast tumor imaging. Results: IC 50 values of DOTA-Galacto-RGD 2 , DOTA-3P-RGD 2 , and DOTA-3P-RGK 2 were calculated to be 27 ± 2, 29 ± 4, 596 ± 48 nM, respectively. The tumor uptake values of 111 In(DOTA-Galacto-RGD 2 ) (6.79 ± 0.98, 6.56 ± 0.56, 4.17 ± 0.61 and 1.09 ± 0.13 %ID/g at 1, 4, 24 and 72 hours p.i., respectively) were almost identical to those of 111 In(DOTA-3P-RGD 2 ) (6.17 ± 1.65, 5.94 ± 0.84, 3.40 ± 0.50 and 0.99 ± 0.20 %ID/g, respectively). 111 In(DOTA-Galacto-RGD 2 ) had a faster clearance from blood and muscle than 111 In(DOTA-3P-RGD 2 ), leading to higher tumor/blood and tumor/muscle ratios. 111 In(DOTA-3P-RGD 2 ) had lower liver uptake and better tumor/liver ratios than 111 In(DOTA-Galacto-RGD 2 ). The tumor uptake of 111 In(DOTA-Galacto-RGD 2 ) and 111 In(DOTA-3P-RGD 2 ) was both integrin α v β 3 and RGD-specific. Imaging data suggest

  18. Radiolabeled cyclic arginine-glycine-aspartic (RGD)-conjugated iron oxide nanoparticles as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer

    Science.gov (United States)

    Deng, Shengming; Zhang, Wei; Zhang, Bin; Hong, Ruoyu; Chen, Qing; Dong, Jiajia; Chen, Yinyiin; Chen, Zhiqiang; Wu, Yiwei

    2015-01-01

    Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) modified with a novel cyclic arginine-glycine-aspartate (RGD) peptide were made and radiolabeled as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer. The probe was tested both in vitro and in vivo to determine its receptor targeting efficacy and feasibility for SPECT and MRI. The radiochemical syntheses of 125I-cRGD-USPIO were accomplished with a radiochemical purity of 96.05 ± 0.33 %. High radiochemical stability was found in fresh human serum and in phosphate-buffered saline. The average hydrodynamic size of 125I-cRGD-USPIO determined by dynamic light scattering was 51.3 nm. Results of in vitro experiments verified the specificity of the radiolabeled nanoparticles to tumor cells. Preliminary biodistribution studies of 125I-radiolabeled cRGD-USPIO in Bcap37-bearing nude mice showed that it had long circulation half-life, high tumor uptake, and high initial blood retention with moderate liver uptake. In vivo tumor targeting and uptake of the radiolabeled nanoparticles in mice model were visualized by SPECT and MRI collected at different time points. Our results strongly indicated that the 125I-cRGD-USPIO could be used as a promising bifunctional radiotracer for early clinical tumor detection with high sensitivity and high spatial resolution by SPECT and MRI.

  19. Spectroscopically Well-Characterized RGD Optical Probe as a Prerequisite for Lifetime-Gated Tumor Imaging

    Directory of Open Access Journals (Sweden)

    Julia Eva Mathejczyk

    2011-11-01

    Full Text Available Labeling of RGD peptides with near-infrared fluorophores yields optical probes for noninvasive imaging of tumors overexpressing αvβ3 integrins. An important prerequisite for optimum detection sensitivity in vivo is strongly absorbing and highly emissive probes with a known fluorescence lifetime. The RGD-Cy5.5 optical probe was derived by coupling Cy5.5 to a cyclic arginine–glycine–aspartic acid–d-phenylalanine–lysine (RGDfK peptide via an aminohexanoic acid spacer. Spectroscopic properties of the probe were studied in different matrices in comparison to Cy5.5. For in vivo imaging, human glioblastoma cells were subcutaneously implanted into nude mice, and in vivo fluorescence intensity and lifetime were measured. The fluorescence quantum yield and lifetime of Cy5.5 were found to be barely affected on RGD conjugation but dramatically changed in the presence of proteins. By time domain fluorescence imaging, we demonstrated specific binding of RGD-Cy5.5 to glioblastoma xenografts in nude mice. Discrimination of unspecific fluorescence by lifetime-gated analysis further enhanced the detection sensitivity of RGD-Cy5.5-derived signals. We characterized RGD-Cy5.5 as a strongly emissive and stable probe adequate for selective targeting of αvβ3 integrins. The specificity and thus the overall detection sensitivity in vivo were optimized with lifetime gating, based on the previous determination of the probes fluorescence lifetime under application-relevant conditions.

  20. An RGD-modified hollow silica@Au core/shell nanoplatform for tumor combination therapy.

    Science.gov (United States)

    Li, Xin; Xing, Lingxi; Hu, Yong; Xiong, Zhijuan; Wang, Ruizhi; Xu, Xiaoying; Du, Lianfang; Shen, Mingwu; Shi, Xiangyang

    2017-10-15

    The combination of chemotherapy and photothermal therapy (PTT) in multifunctional nanoplatforms to improve cancer therapeutic efficacy is of great significance while it still remains to be a challenging task. Herein, we report Au nanostar (NS)-coated hollow mesoporous silica nanocapsules (HMSs) with surface modified by arginine-glycine-aspartic acid (RGD) peptide as a drug delivery system to encapsulate doxorubicin (DOX) for targeted chemotherapy and PTT of tumors. Au NSs-coated HMSs core/shell nanocapsules (HMSs@Au NSs) synthesized previously were conjugated with RGD peptide via a spacer of polyethylene glycol (PEG). We show that the prepared HMSs@Au-PEG-RGD NSs are non-cytotxic in the given concentration range, and have a DOX encapsulation efficiency of 98.6±0.7%. The designed HMSs@Au-PEG-RGD NSs/DOX system can release DOX in a pH/NIR laser dual-responsive manner. Importantly, the formed HMSs@Au-PEG-RGD NSs/DOX nanoplatform can specifically target cancer cells overexpressing α v β 3 intergrin and exert combination chemotherapy and PTT efficacy to the cells in vitro and a xenografted tumor model in vivo. Our results suggest that the designed HMSs@Au-PEG-RGD NSs/DOX nanoplatform may be used for combination chemotherapy and PTT of tumors. We demonstrate a convenient approach to preparing a novel RGD-targeted drug delivery system of HMSs@Au-PEG-RGD NSs/DOX that possesses pH/NIR laser dual-responsive drug delivery performance for combinational chemotherapy and PTT of tumors. The developed Au NS-coated HMS capsules have both merits of HMS capsules that can be used for high payload drug loading and Au NSs that have NIR laser-induced photothermal conversion efficiency (70.8%) and can be used for PTT of tumors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

    Directory of Open Access Journals (Sweden)

    Chu YC

    2017-02-01

    Full Text Available Yongchao Chu,1,* Ning Chen,2,* Huajun Yu,2,* Hongjie Mu,1 Bin He,1 Hongchen Hua,1 Aiping Wang,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: A nanoparticle (NP was developed to target choroidal neovascularization (CNV via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC and transactivated transcription (TAT (RKKRRQRRRC peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol–poly(lactic-co-glycolic acid. The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs

  2. Survival, proliferation and differentiation enhancement of neural stem cells cultured in three-dimensional polyethylene glycol-RGD hydrogel with tenascin.

    Science.gov (United States)

    Naghdi, Pejman; Tiraihi, Taki; Ganji, Fariba; Darabi, Shehram; Taheri, Taher; Kazemi, Hadi

    2016-03-01

    Polyethylene glycol hydrogel (PEG) conjugated with arginyl glycyl aspartic acid (RGD) (PEG-RGD) has been considered to be a scaffold in three-dimensional (3D) culture that improves neurite outgrowth; on the other hand, tenascin C controls neural growth and differentiation. In this study, the effect of a combined RGD and tenascin C mixture in 3D culture (3D-PEG-RGD-TnC) on the survival, growth and differentiation of neural stem cells. The viability of the culture has been evaluated by live/dead assay and the results show that the viability of NSCs in 3D-PEG-RGD-TnC is significantly higher than its value in 3D-PEG-RGD. The proliferation was evaluated by MTS test and was found to be slightly improved but statistically not significant. Accordingly, the differentiation was evaluated by immunoreactivity to nestin, neurofilament 68, neurofilament 160, neurofilament 200 and GFAP; and the expression of nestin, neuro D, musashi1, β-tubulin III, GFAP, MBP and Oct4 was studied using RT-PCR. The results showed enhancement of the differentiation of NSCs into the neuronal phenotype in 3D-PEG-RGD-TnC. The morphology of NSCs cultured in 3D-PEG-RGD-TnC showed neurite outgrowths and increase in the contact between the differentiated cells' extensions. The conclusion of this study was that NSC survival, proliferation and differentiation are enhanced when the cells are cultured in 3D-PEG-RGD-TnC. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Bioabsorbable bypass grafts biofunctionalised with RGD have enhanced biophysical properties and endothelialisation tested in vivo

    Directory of Open Access Journals (Sweden)

    Larisa V Antonova

    2016-05-01

    Full Text Available Small diameter arterial bypass grafts are considered as unmet clinical need since the current grafts have poor patency of 25% within 5 years. We have developed a 3D scaffold manufactured from natural and synthetic biodegradable polymers, poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV and poly(ε-caprolactone (PCL, respectively. Further to improve the biophysical properties as well as endothelialisation, the grafts were covalently conjugated with arginine-glycine-aspartic acid (RGD bioactive peptides. The biophysical properties as well as endothelialisation of PHBV/PCL and PCL 2 mm diameter bypass grafts were assessed with and without biofunctionalisation with RGD peptides in vitro and in vivo. Morphology of the grafts was assessed by scanning electron microscopy, whereas physico-mechanical properties were evaluated using a physiological circulating system equipped with a state of art ultrasound vascular wall tracking system. Endothelialisation of the grafts in vitro and in vivo were assessed using a cell viability assay and rat abdominal aorta replacement model, respectively. The biofunctionalisation with RGD bioactive peptides decreased mean fiber diameter and mean pore area in PHBV/PCL grafts; however, this was not the case for PCL grafts. Both PHBV/PCL and PCL grafts with RGD peptides had lower durability compared to those without; these durability values were similar to those of internal mammary artery. Modification of PHBV/PCL and PCL grafts with RGD peptides increased endothelial cell viability in vitro by a factor of 8 and enhanced the formation of an endothelial cell monolayer in vivo one month postimplantation. In conclusion, PHBV/PCL small-caliber graft can be a suitable 3D scaffold for the development of a tissue engineering arterial bypass graft.

  4. Cyclic RGD peptide-modified liposomal drug delivery system: enhanced cellular uptake in vitro and improved pharmacokinetics in rats

    Directory of Open Access Journals (Sweden)

    Chen Z

    2012-07-01

    Full Text Available Zhongya Chen,1,2 Jiaxin Deng,1,2 Yan Zhao,1,2 Tao Tao1,21National Pharmaceutical Engineering Research Center, 2Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaBackground: Integrins αvβ3 and αvβ5, both of which specifically recognize the Arg-Gly-Asp (RGD motif, are overexpressed on many solid tumors and in tumor neovasculature. Thus, coupling the RGD motif to the liposomal surface for achieving active targeting can be a promising strategy for the treatment of tumors.Methods: Cyclo(Arg-Gly-Asp-D-Phe-Cys (cRGD was covalently coupled with the liposomal membrane surface, followed by coating with poly(ethylene glycol (PEG using the post-insertion technique. The coupling efficiency of cRGD was determined. Doxorubicin as a model anticancer drug was loaded into liposomes using an ammonium sulfate gradient method to investigate the encapsulation efficiency, cellular uptake by the integrin-overexpressing human glioma cell line U87MG in vitro, and pharmacokinetic properties in Sprague-Dawley rats.Results: cRGD was conjugated to the liposomal surface by a thiol-maleimide coupling reaction. The coupling efficiency reached 98%. The encapsulation efficiency of doxorubicin in liposomes was more than 98%. The flow cytometry test result showed that cRGD-modified liposomes (RGD-DXRL-PEG had higher cell uptake by U87MG cells, compared with nontargeted liposomes (DXRL-PEG. The cellular uptake was significantly inhibited in the presence of excess free cRGD. Both the targeted (t1/2 = 24.10 hours and non-targeted (t1/2 = 25.32 hours liposomes showed long circulating properties in rat plasma. The area under the curve of the targeted and nontargeted liposomes was 6.4-fold and 8.3-fold higher than that of doxorubicin solution, respectively.Conclusion: This study indicates preferential targeting and long circulating properties for cRGD-modified liposomes in vivo, which could be used as

  5. Multifunctional gold nanostar conjugates for tumor imaging and combined photothermal and chemo-therapy.

    Science.gov (United States)

    Chen, Haiyan; Zhang, Xin; Dai, Shuhang; Ma, Yuxiang; Cui, Sisi; Achilefu, Samuel; Gu, Yueqing

    2013-01-01

    Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi-functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively. The NIR contrast agent Au-cRGD-MPA was shown to have low cytotoxicity. Using tumor cells and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor-targeting capability mediated by RGD peptide binding to its over-expressed receptor on the tumor cells. The multi-therapeutic analogue, Au-cRGD-DOX, integrates targeting tumor, chemotherapy and photo-thermotherapy into a single system. The synergistic effect of photo-thermal therapy and chemotherapy was demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing mouse models. The viability of MDA-MB-231 cells was only 40 % after incubation with Au-cRGD-DOX and irradiation with NIR light. Both tail vein and intratumoral injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase. These results indicate that the multifunctional nanoconstruct is a promising combined therapeutic agent for tumor-targeting treatment, with the potential to enhance the anti-cancer treatment outcomes.

  6. Improving Tumor Uptake and Pharmacokinetics of 64Cu-Labeled Cyclic RGD Peptide Dimers with Gly3 and PEG4 Linkers

    OpenAIRE

    Shi, Jiyun; Kim, Young-Seung; Zhai, Shizhen; Liu, Zhaofei; Chen, Xiaoyuan; Liu, Shuang

    2009-01-01

    Radiolabeled cyclic RGD (Arg-Gly-Asp) peptides represent a new class of radiotracers with potential for the early tumor detection and non-invasive monitoring of tumor metastasis and therapeutic response in cancer patients. This report describes the synthesis of two cyclic RGD peptide dimer conjugates, DOTA-PEG4-E[PEG4-c(RGDfK)]2 (DOTA-3PEG4-dimer: DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and DOTA-G3-E[G3-c(RGDfK)]2 ...

  7. Radiolabelled RGD peptides for imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gaertner, F.C.; Schwaiger, M.; Beer, A.J. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kessler, H. [Technische Universitaet Muenchen, Institute for Advanced Study and Center of Integrated Protein Science, Department of Chemistry, Garching (Germany); King Abdulaziz University, Chemistry Department, Faculty of Science, Jeddah (Saudi Arabia); Wester, H.-J. [Institute for Pharmaceutical Radiochemistry, Garching (Germany)

    2012-02-15

    Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin {alpha}{sub v}{beta}{sub 3}. For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of {alpha}{sub v}{beta}{sub 3} expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy. (orig.)

  8. Improvements of RGD3 TLD reader

    International Nuclear Information System (INIS)

    Zhao Jianxing; Wang Jiaqi; Li Yuanfang; Wu Furong; Xiao Wuyun

    1999-01-01

    The author summarized the main features of the improved RGD3 TLD reader. Through a large number of experiments some persuasive data are obtained, which show that an remarkable improvement has been achieved, especially in its stability to the standard illuminates, data dispersivity, and effectiveness to glow curves analysis. Working with the newly developed data processing software, the comprehensive performance of the whole system will be enhanced greatly

  9. Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.

    Science.gov (United States)

    Chen, Zhanfei; Lian, Fen; Wang, Xiaoqian; Chen, Yanling; Tang, Nanhong

    The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine-glycine-aspartic acid (RGD) peptide. Our studies demonstrate that RGD-polyethylene glycol (PEG)-PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT-MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system.

  10. Peptide-Conjugated Quantum Dots Act as the Target Marker for Human Pancreatic Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Shuang-ling Li

    2016-03-01

    Full Text Available Background/Aims: In the present study, we describe a novel and straightforward approach to produce a cyclic- arginine-glycine-aspartic (RGD-peptide-conjugated quantum dot (QD probe as an ideal target tumor biomarker. Due to its specific structure, the probe can be used for targeted imaging of pancreatic carcinoma cells. Methods: Pancreatic carcinoma cells were routinely cultured and marked with QD-RGD probe. The QD-RGD probe on the fluorescence-labeled cancer cell was observed by fluorescence microscopy and laser confocal microscopy. Cancer cell viability was detected by MTT assay after culturing with QD-RGD probe. Results: Fluorescence microscopy and laser confocal microscopy displayed that 10nmol/L QD-RGD probe was able to effectively mark pancreatic carcinoma cells. In comparison with organic dyes and fluorescent proteins, the quantum dot-RGD probe had unique optical and electronic properties. Conclusion: QD-RGD probe has a low cytotoxicity with an excellent optical property and biocompatibility. These findings support further evaluation of QD-RGD probes for the early detection of pancreatic cancer.

  11. Enhancement of the uptake and cytotoxic activity of doxorubicin in cancer cells by novel cRGD-semipeptide-anchoring liposomes.

    Science.gov (United States)

    Battistini, Lucia; Burreddu, Paola; Sartori, Andrea; Arosio, Daniela; Manzoni, Leonardo; Paduano, Luigi; D'Errico, Gerardino; Sala, Roberto; Reia, Laura; Bonomini, Sabrina; Rassu, Gloria; Zanardi, Franca

    2014-07-07

    Novel liposemipeptides hanging cyclic azabicycloalkane-RGD or aminoproline-RGD terminals were synthesized and incorporated into liposomal nanoparticles cAba/cAmpRGD-LNP5 3C/3D. Liposomes with similar composition and lacking semipeptide conjugates were constructed for comparison (LNP, 3A), and physical encapsulation of the anticancer doxorubicin drug in both targeted and untargeted liposomes was accomplished. Microstructural analysis performed by dynamic light scattering (DLS), small-angle neutron scattering (SANS), and electron paramagnetic resonance (EPR) revealed that the conjugated nanoparticles presented an average size of 80 nm and were constituted by 5 nm thick unilamellar liposome bilayer. Flow cytometry and fluorescent microscopy studies showed that 3C-DOXO and 3D-DOXO efficiently delivered the drug into the nuclei of both quiescent and proliferating cells even in a high serum concentration environment. The uptake of doxorubicin when carried by liposomes was faster than that of the free drug, and 30 min incubation was sufficient to load cell nuclei with doxorubicin. Targeted liposomes significantly induced cell death of human breast adenocarcinoma MCF7 cells (IC50 = 144 nM, 3C-DOXO; IC50 = 274 nM, 3D-DOXO), about 2- to 6-fold more potent than free doxorubicin or 3A-DOXO controls (IC50 = 527 and 854 nM, respectively). These results suggest that cAba/cAmpRGD liposomal nanoparticles hold promise for the rapid and efficient delivery of chemotherapeutic agents to αVβ3-expressing tumor cells.

  12. Preparation and evaluation of a68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.

    Science.gov (United States)

    Velikyan, Irina; Lindhe, Örjan

    2018-01-01

    Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced 68 Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to α v β 3 integrin receptors. The main objective of this study was to develop a method for 68 Ga-labeling of RGD containing bicyclic octapeptide ([ 68 Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [ 68 Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full 68 Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [ 68 Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis.

  13. RGD(F/S/V-Dex: towards the development of novel, effective, and safe glucocorticoids

    Directory of Open Access Journals (Sweden)

    Jiang X

    2016-03-01

    Full Text Available Xueyun Jiang,1 Ming Zhao,1,2 Yuji Wang,1 Haimei Zhu,1 Shurui Zhao,1 Jianhui Wu,1 Yuanbo Song,3 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Guangxi Pusen Biotechnology Co. Ltd., Nanning, Guangxi, People’s Republic of China Abstract: Dexamethasone (Dex is an effective glucocorticoid in treating inflammation and preventing rejection reaction. However, the side effects limit its clinical application. To improve its druggable profile, the conjugates of RGD-peptide-modified Dex were presented and their enhanced anti-inflammation activity, minimized osteoporotic action, and nanoscaled assembly were explored. (RGD stands for Arg-Gly-Asp. Standard single letter biochemical abbreviations for amino acids have been used throughout this paper. In respect of the rejection reaction, the survival time of the implanted myocardium of the mice treated with 1.43 µmol/kg/d of the conjugates for 15 consecutive days was significantly longer than that of the mice treated with 2.5 µmol/kg/d of Dex, and the conjugates, but not Dex, exhibited no toxic action. At a single dose of 14.3 µmol/kg (100 times minimal effective dose, 0.143 µmol/kg, the conjugates induced no liver, kidney, or systemic toxicity. At the dose of 1.43 µmol/kg, the conjugates, but not Dex, prolonged the bleeding time of the mice, and inhibited the thrombosis of the rats. In water and rat plasma, the conjugates formed nanoparticles of 14–250 and 101–166 nm in diameter, respectively. Since the nanoparticles of ~100 nm in size cannot be entrapped by macrophages in the circulation, RGDF-Dex would particularly be worthy

  14. Utilization of a novel electrochemical 90Sr/90Y generator for the preparation of 90Y-labeled RGD peptide dimer in clinically relevant dose

    International Nuclear Information System (INIS)

    Chakraborty, Sudipta; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh; Sarma, Haladhar Dev

    2014-01-01

    The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dose of 90 Y-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)] 2 [DOTA-(RGD) 2 ] for in vivo targeted therapy utilizing 90 Y obtained from a novel electrochemical 90 Sr/ 90 Y generator. The performance of the generator was evaluated to ensure its suitability for providing 90 Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. 90 Y-DOTA-(RGD) 2 was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∝ 3.8 GBq) of 90 Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing 90 Y labeled cyclic RGD peptides for targeted therapy of tumors over-expressing integrin-α ν β 3 receptors. (orig.)

  15. Potent peptide-conjugated silicon phthalocyanines for tumor photodynamic therapy.

    Science.gov (United States)

    Liu, Qian; Pang, Mingpei; Tan, Sihai; Wang, Jin; Chen, Qingle; Wang, Kai; Wu, Wenjie; Hong, Zhangyong

    2018-01-01

    Phthalocyanines (Pcs) are a group of promising photosensitizers for use in photodynamic therapy (PDT). However, their extremely low solubility and their strong tendency to aggregate in aqueous solution greatly restrict their application. Conjugation of Pc macrocycles with peptide ligands could be a very useful strategy to optimize the physical properties of Pcs not only by increasing their water solubility and reducing their aggregation but also by endowing the conjugates with a tumor-targeting capability. To develop highly potent photosensitizers for tumor PDT, we prepared new peptide-conjugated photosensitizers using silicon Pc (SiPc), which has much higher photodynamic activity than zinc Pcs, as the light activation moiety and the cRGDfK peptide (or simply cRGD) as the peptide moiety. A polyethylene glycol linker and an extra carboxylic acid group were also tested for introduction into the conjugates to optimize the conjugate structure. The conjugates' photophysical and photodynamic behaviors were then carefully evaluated and compared using in vitro and in vivo experiments. One of the prepared conjugates, RGD-(Linker) 2 -Glu-SiPc, showed excellent physical properties and photodynamic activity, with an EC 50 (half maximal effective concentration) of 10-20 nM toward various cancer cells. This conjugate eradicated human glioblastoma U87-MG tumors in a xenograft murine tumor model after only one dose of photodynamic treatment, with no tumor regrowth during observation for up to 35 days. The conjugate RGD-(Linker) 2 -Glu-SiPc thus showed highly promising potential for use in tumor treatment.

  16. A collagen-targeted biomimetic RGD peptide to promote osteogenesis.

    Science.gov (United States)

    Visser, Rick; Arrabal, Pilar M; Santos-Ruiz, Leonor; Fernandez-Barranco, Raul; Becerra, Jose; Cifuentes, Manuel

    2014-01-01

    Osteogenesis is a complex, multifactorial process in which many different signals interact. The bone morphogenetic proteins (BMPs) are the most potent inducers of osteoblastic differentiation, although very high doses of BMPs in combination with collagen type I formulations have to be used for clinical applications. Although integrin-binding arginine-glycine-aspartic acid (RGD) biomimetic peptides have shown some promising abilities to promote the attachment of cells to biomaterials and to direct their differentiation, the linking of these peptides to collagen sponges usually implies chemical manipulation steps. In this study, we describe the design and characterization of a synthetic collagen-targeted RGD biomimetic (CBD-RGD) peptide formed from a collagen-binding domain derived from the von Willebrand factor and the integrin-binding RGD sequence. This peptide was demonstrated to bind to absorbable collagen type I sponges (ACSs) without performing any chemical linking, and to induce the differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells. Furthermore, in vivo experiments showed that ACSs functionalized with CBD-RGD and loaded with a subfunctional dose of BMP-2-formed ectopic bone in rats, while nonfunctionalized sponges loaded with the same amount of BMP-2 did not. These results indicate that the combination of this biomimetic peptide with the currently used collagen+BMP system might be a promising approach to improve osteogenesis and to reduce the doses of BMPs needed in clinical orthopedics.

  17. Status and Advances of RGD Molecular Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning YUE

    2014-12-01

    Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  18. Synthesis, analysis and biological evaluation of new RGD mimetics

    Czech Academy of Sciences Publication Activity Database

    Balacheva, A. A.; Lambev, M. K.; Pashov, I.; Detcheva, R. L.; Sázelová, Petra; Momekov, G. Ts.; Kašička, Václav; Pajpanova, T. I.; Golovinsky, E. V.

    2017-01-01

    Roč. 49, SI E (2017), s. 7-10 ISSN 0324-1130. [Bulgarian Peptide Symposium /7./. Blagoevgrad, 10.06.2016-12.06.2016] Institutional support: RVO:61388963 Keywords : RGD * biologically active peptides * cytotoxicity Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 0.238, year: 2016

  19. Antitumor magnetic hyperthermia induced by RGD-functionalized Fe3O4 nanoparticles, in an experimental model of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Oihane K. Arriortua

    2016-10-01

    Full Text Available This work reports important advances in the study of magnetic nanoparticles (MNPs related to their application in different research fields such as magnetic hyperthermia. Nanotherapy based on targeted nanoparticles could become an attractive alternative to conventional oncologic treatments as it allows a local heating in tumoral surroundings without damage to healthy tissue. RGD-peptide-conjugated MNPs have been designed to specifically target αVβ3 receptor-expressing cancer cells, being bound the RGD peptides by “click chemistry” due to its selectivity and applicability. The thermal decomposition of iron metallo-organic precursors yield homogeneous Fe3O4 nanoparticles that have been properly functionalized with RGD peptides, and the preparation of magnetic fluids has been achieved. The nanoparticles were characterized by transmission electron microscopy (TEM, vibrating sample magnetometry (VSM, electron magnetic resonance (EMR spectroscopy and magnetic hyperthermia. The nanoparticles present superparamagnetic behavior with very high magnetization values, which yield hyperthermia values above 500 W/g for magnetic fluids. These fluids have been administrated to rats, but instead of injecting MNP fluid directly into liver tumors, intravascular administration of MNPs in animals with induced colorectal tumors has been performed. Afterwards the animals were exposed to an alternating magnetic field in order to achieve hyperthermia. The evolution of an in vivo model has been described, resulting in a significant reduction in tumor viability.

  20. Data on interaction between adeno-associated virus and U87 cell via cRGD chemical modification

    Directory of Open Access Journals (Sweden)

    Chuanling Zhang

    2016-06-01

    Full Text Available RGD tripeptide is a specific, high-affinity ligand for integrin, which is highly expressed in cancer cells. We previously reported that cRGD chemically modified AAV2 (AAV2N587+1/azido+RGD showed significantly enhanced infectivity compared to RGD genetically inserted AAV2 (AAV2N587+RGD (10.1016/j.biomaterials.2015.11.066 [1]. Herein we provide the binding ability analysis of RGD modified AAV2 and U87 cell by flow cytometry and the theoretical working model of RGD–αvβ3 integrin interaction.

  1. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide

    International Nuclear Information System (INIS)

    Dijkgraaf, Ingrid; Liu, Shuang; Kruijtzer, John A.W.; Soede, Annemieke C.; Oyen, Wim J.G.; Liskamp, Rob M.J.; Corstens, Frans H.M.; Boerman, Otto C.

    2007-01-01

    Introduction: Due to the selective expression of the α v β 3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study, we systematically investigated the effects of linker modification between two cyclic RGD sequences and DOTA (1,4,7,10-tetraazadodecane-N,N',N ' ,N'''-tetraacetic acid) on the in vitro and in vivo characteristics of the tracer. Methods: A dimeric RGD peptide was synthesized and conjugated either directly with DOTA or via different linkers: PEG 4 (polyethylene glycol), glutamic acid or lysine. The RGD peptides were radiolabeled with 111 In, and their in vitro and in vivo α v β 3 -binding characteristics were determined. Results: LogP values varied between -2.82±0.06 and -3.95±0.33. The IC 50 values for DOTA-E-[c(RGDfK)] 2 , DOTA-PEG 4 -E-[c(RGDfK)] 2 , DOTA-E-E-[c(RGDfK)] 2 and DOTA-K-E-[c(RGDfK)] 2 were comparable. Two hours after injection, the tumor uptakes of the 111 In-labeled compounds were not significantly different. The kidney accumulation of [ 111 In]-DOTA-K-E-[c(RGDfK)] 2 [4.05±0.20% of the injected dose per gram (ID/g)] was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (2.63±0.19% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.16±0.21% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.12±0.09% ID/g) was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (1.64±0.1% ID/g; P 111 In]-DOTA-K-E-[c(RGDfK)] 2 (1.52±0.04% ID/g; P v β 3 and tumor uptake. Insertion of lysine caused enhanced kidney retention; that of glutamic acid also resulted in enhanced retention in the kidneys. PEG 4 appeared to be the most suitable linker as compared with glutamic acid and lysine because it has the highest tumor-to-blood ratio and the lowest uptake in the kidney and liver

  2. Catalyst-Free Conjugation and In Situ Quantification of Nanoparticle Ligand Surface Density Using Fluorogenic Cu-Free Click Chemistry

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming; Sun, Honghao; Berg, Rolf Henrik

    2011-01-01

    A highly efficient method for functionalizing nanoparticles and directly quantifying conjugation efficiency and ligand surface density has been developed. Attachment of 3-azido-modifed RGD-peptides to PEGylated liposomes was achieved by using Cu-free click conditions. Upon coupling a fluorophore ...

  3. The RGD finger of Del-1 is a unique structural feature critical for integrin binding

    Energy Technology Data Exchange (ETDEWEB)

    Schürpf, Thomas; Chen, Qiang; Liu, Jin-huan; Wang, Rui; Springer, Timothy A.; Wang, Jia-huai (Harvard-Med)

    2012-11-13

    Developmental endothelial cell locus-1 (Del-1) glycoprotein is secreted by endothelial cells and a subset of macrophages. Del-1 plays a regulatory role in vascular remodeling and functions in innate immunity through interaction with integrin {alpha}{sub V}{beta}{sub 3}. Del-1 contains 3 epidermal growth factor (EGF)-like repeats and 2 discoidin-like domains. An Arg-Gly-Asp (RGD) motif in the second EGF domain (EGF2) mediates adhesion by endothelial cells and phagocytes. We report the crystal structure of its 3 EGF domains. The RGD motif of EGF2 forms a type II' {beta} turn at the tip of a long protruding loop, dubbed the RGD finger. Whereas EGF2 and EGF3 constitute a rigid rod via an interdomain calcium ion binding site, the long linker between EGF1 and EGF2 lends considerable flexibility to EGF1. Two unique O-linked glycans and 1 N-linked glycan locate to the opposite side of EGF2 from the RGD motif. These structural features favor integrin binding of the RGD finger. Mutagenesis data confirm the importance of having the RGD motif at the tip of the RGD finger. A database search for EGF domain sequences shows that this RGD finger is likely an evolutionary insertion and unique to the EGF domain of Del-1 and its homologue milk fat globule-EGF 8. The RGD finger of Del-1 is a unique structural feature critical for integrin binding.

  4. Utilization of a novel electrochemical {sup 90}Sr/{sup 90}Y generator for the preparation of {sup 90}Y-labeled RGD peptide dimer in clinically relevant dose

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sudipta; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, Haladhar Dev [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

    2014-09-01

    The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dose of {sup 90}Y-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)]{sub 2} [DOTA-(RGD){sub 2}] for in vivo targeted therapy utilizing {sup 90}Y obtained from a novel electrochemical {sup 90}Sr/{sup 90}Y generator. The performance of the generator was evaluated to ensure its suitability for providing {sup 90}Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. {sup 90}Y-DOTA-(RGD){sub 2} was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∝ 3.8 GBq) of {sup 90}Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing {sup 90}Y labeled cyclic RGD peptides for targeted therapy of tumors over-expressing integrin-α{sub ν}β{sub 3} receptors. (orig.)

  5. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging.

    Science.gov (United States)

    Haedicke, Katja; Brand, Christian; Omar, Murad; Ntziachristos, Vasilis; Reiner, Thomas; Grimm, Jan

    2017-06-01

    Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher ® (BHQ) dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to α v β 3 -integrin expressing glioblastoma cell spheroids in vitro . The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo . Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  6. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Katja Haedicke

    2017-06-01

    Full Text Available Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher® (BHQ dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to αvβ3-integrin expressing glioblastoma cell spheroids in vitro. The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo. Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  7. Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model

    Directory of Open Access Journals (Sweden)

    Anton V Borovjagin

    2012-02-01

    Full Text Available Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds, genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach.This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, “Δ24DoubleRGD.” Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD motif incorporated into both fiber and capsid protein IX (pIX and its oncolytic efficacy was evaluated in ovarian cancer. In vitro analysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cells in vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.

  8. Synthesis and Bioevaluation of Iodine-131 Directly Labeled Cyclic RGD-PEGylated Gold Nanorods for Tumor-Targeted Imaging

    Directory of Open Access Journals (Sweden)

    Yingying Zhang

    2017-01-01

    Full Text Available Introduction. Radiolabeled gold nanoparticles play an important role in biomedical application. The aim of this study was to prepare iodine-131 (131I-labeled gold nanorods (GNRs conjugated with cyclic RGD and evaluate its biological characteristics for targeted imaging of integrin αvβ3-expressing tumors. Methods. HS-PEG(5000-COOH molecules were applied to replace CTAB covering the surface of bare GNRs for better biocompatibility, and c(RGDfK peptides were conjugated onto the carboxyl terminal of GNR-PEG-COOH via EDC/NHS coupling reactions. The nanoconjugate was characterized, and 131I was directly tagged on the surface of GNRs via AuI bonds for SPECT/CT imaging. We preliminarily studied the characteristics of the probe and its feasibility for tumor-targeting SPECT/CT imaging. Results. The [131I]GNR-PEG-cRGD probe was prepared in a simple and rapid manner and was stable in both PBS and fetal bovine serum. It targeted selectively and could be taken up by tumor cells mainly via integrin αvβ3-receptor-mediated endocytosis. In vivo imaging, biodistribution, and autoradiography results showed evident tumor uptake in integrin αvβ3-expressing tumors. Conclusions. These promising results showed that this smart nanoprobe can be used for angiogenesis-targeted SPECT/CT imaging. Furthermore, the nanoprobe possesses a remarkable capacity for highly efficient photothermal conversion in the near-infrared region, suggesting its potential as a multifunctional theranostic agent.

  9. Preparation of the radiopharmaceutical 99m Tc-HYNIC-cyclo-Lys-D-Phe-RGD for In vivo image of integrines

    International Nuclear Information System (INIS)

    Hernandez H, E.

    2007-01-01

    The diagnostic of some pathological processes by means of images constitutes one of the used methods in the determination of the origin, condition and/or evolution of one illness. The use of contrast agents in conjunction with other techniques help to the obtaining and visualization of complex systems, among these we can find to those radiopharmaceuticals used in nuclear medicine to visualize diverse organs and corporal systems. At the moment it is sought to develop a radiopharmaceutical of third generation that can be used for image In vivo of integrines with the purpose of detecting angio genesis processes, that which would allow to diagnose in way it specifies a wide range of primary tumors and their metastasis. Presently work it developed the radiopharmaceutical 99m Tc-HYNIC-cycle-Lys-D-Phe-RGD, likewise the good conditions were determined for the formation of this complex. The HYNIC was employee as chelating agent, using as co ligands EDDA and Tricine for to complete the sphere of coordination of the 99m Tc. The conjugated HYNIC-RGD was synthesized, purified, characterized and radiolabelled In situ with 99m Tc using High pressure liquid chromatography as analysis method in Reverse Phase (RP-HPLC). By this way it was developed the lyophilized formulation for its instantaneous labelled to which were carried out quality control tests. The one conjugated was obtained free of impurities, showing stability at same as their complex formed with 99m Tc. The analysis method was validated turning out to be necessary, exact, lineal and specific for the quantification of the analyte of interest. The lyophilized formulation showed a radiochemical purity bigger than 95%, besides being sterile and free of pyrogens. The biodistribution tests in athymic mice with induced tumors showed that the radiopharmaceutical was united mainly to the tumor and that this it was excreted mainly for renal via. (Author)

  10. Iminodiacetic acid as bifunctional linker for dimerization of cyclic RGD peptides

    International Nuclear Information System (INIS)

    Xu, Dong; Zhao, Zuo-Quan; Chen, Shu-Ting; Yang, Yong; Fang, Wei; Liu, Shuang

    2017-01-01

    Introduction: In this study, I2P-RGD 2 was used as the example to illustrate a novel approach for dimerization of cyclic RGD peptides. The main objective of this study was to explore the impact of bifunctional linkers (glutamic acid vs. iminodiacetic acid) on tumor-targeting capability and excretion kinetics of the 99m Tc-labeled dimeric cyclic RGD peptides. Methods: HYNIC-I2P-RGD 2 was prepared by reacting I2P-RGD 2 with HYNIC-OSu in the presence of diisopropylethylamine, and was evaluated for its α v β 3 binding affinity against 125 I-echistatin bound to U87MG glioma cells. 99m Tc-I2P-RGD 2 was prepared with high specific activity (~185 GBq/μmol). The athymic nude mice bearing U87MG glioma xenografts were used to evaluate its biodistribution properties and image quality in comparison with those of 99m Tc-3P-RGD 2 . Results: The IC 50 value for HYNIC-I2P-RGD 2 was determined to be 39 ± 6 nM, which was very close to that (IC 50 = 33 ± 5 nM) of HYNIC-3P-RGD 2 . Replacing glutamic acid with iminodiacetic acid had little impact on α v β 3 binding affinity of cyclic RGD peptides. 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 shared similar tumor uptake values over the 2 h period, and its α v β 3 -specificity was demonstrated by a blocking experiment. The uptake of 99m Tc-I2P-RGD 2 was significantly lower than 99m Tc-3P-RGD 2 in the liver and kidneys. The U87MG glioma tumors were visualized by SPECT with excellent contrast using both 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 . Conclusion: Iminodiacetic acid is an excellent bifunctional linker for dimerization of cyclic RGD peptides. Bifunctional linkers have significant impact on the excretion kinetics of 99m Tc radiotracers. Because of its lower liver uptake and better tumor/liver ratios, 99m Tc-I2P-RGD 2 may have advantages over 99m Tc-3P-RGD 2 for diagnosis of tumors in chest region. -- Graphical abstract: This report presents novel approach for dimerization of cyclic RGD peptides using iminodiacetic acid as a

  11. Targeting B16 tumors in vivo with peptide-conjugated gold nanoparticles

    Science.gov (United States)

    Poon, Wilson; Zhang, Xuan; Bekah, Devesh; Teodoro, Jose G.; Nadeau, Jay L.

    2015-07-01

    This study examines the effects of polyethylene glycol (PEG) and peptide conjugation on the biodistribution of ultrasmall (2.7 nm) gold nanoparticles in mice bearing B16 melanoma allografts. Nanoparticles were delivered intravenously, and biodistribution was measured at specific timepoints by organ digestion and inductively coupled plasma mass spectrometry. All major organs were examined. Two peptides were tested: the cyclic RGD peptide (cRGD, which targets integrins); and a recently described peptide derived from the myxoma virus. We found the greatest specific tumor delivery using the myxoma peptide, with or without PEGylation. Un-PEGylated cRGD performed poorly, but PEGylated RGD showed a significant transient collection in the tumor. Liver and kidney were the primary targets of all constructs. None of the particles were able to cross the blood-brain barrier. Although it was able to deliver Au to B16 cells, the myxoma peptide did not show any cytotoxic activity against these cells, in contrast to previous reports. These results indicate that the effect of passive targeting by PEGylation and active targeting by peptides can be independent or combined, and that they should be evaluated on a case-by-case basis when designing new nanosystems for targeted therapies. Both myxoma peptide and cRGD should be considered for specific targeting to melanoma, but a thorough investigation of the cytotoxicity of the myxoma peptide to different cell lines remains to be performed.

  12. High affinity recognition of a Phytophthora protein by Arabidopsis via an RGD motif

    NARCIS (Netherlands)

    Senchou, V.; Weide, R.L.; Carrasco, A.; Bouyssou, H.; Pont-Lezica, R.; Govers, F.; Canut, H.

    2004-01-01

    The RGD tripeptide sequence, a cell adhesion motif present in several extracellular matrix proteins of mammalians, is involved in numerous plant processes. In plant-pathogen interactions, the RGD motif is believed to reduce plant defence responses by disrupting adhesions between the cell wall and

  13. Topical application of palmitoyl-RGD reduces human facial wrinkle formation in Korean women.

    Science.gov (United States)

    Bae, Jung-Soo; Kim, Jong Mook; Kim, Jung Yun; Choi, Chi Ho; Kim, Ju Yeon; Moon, Won Kang; Lee, Min Sup; Moon, Sung Ho; Lim, Joo Hyuck; Park, Sung Jun; Lee, Jin Seo; Song, Hyunnam; Kim, Beom Joon; Park, Young Jun; Seo, Jin Seok

    2017-10-01

    Maintaining a youthful appearance is a common desire among the aging population. Loss of elasticity and dermal density constitutes major causes of wrinkle formation during skin aging. In particular, periorbital wrinkles comprise the critical assessment point of skin aging. To address these issues, cosmetic industries have been making increasing efforts to develop efficient agents against wrinkle formation. Arg-Gly-Asp (RGD) is a tripeptide sequence used for surface coating because of its integrin-binding property. However, its pharmacological properties on skin have not yet been studied. Here, we synthesize the novel palmitoyl-Arg-Gly-Asp (Palm-RGD) and investigate its effects on periorbital wrinkle formation by clinical and in vitro studies. We observed that Palm-RGD cream application for 12 weeks decreased global photodamage and skin roughness (R1, R2, R3, and Ra) scores without causing skin irritation. In addition, topical application of Palm-RGD cream time-dependently increased skin elasticity and dermal density. An in vitro study using human dermal fibroblasts (HDFs) demonstrated increased type I procollagen production by Palm-RGD treatment. Furthermore, Palm-RGD suppressed MMP-1 expression in HDFs. Our results demonstrate that Palm-RGD has protective effects against wrinkle formation, likely through the activation of collagen expression and the protection against collagen degradation. Therefore, Palm-RGD could be used as a potential agent for the prevention of wrinkle formation consequent to aging.

  14. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

  15. Enhanced transduction and replication of RGD-fiber modified adenovirus in primary T cells.

    Directory of Open Access Journals (Sweden)

    Sadhak Sengupta

    2011-03-01

    Full Text Available Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR. T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD.A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replication-competent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35-45% of splenic T cells were transduced by Ad-RGD.Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary T cells of both murine and human origin.

  16. Functionalization of the PEG Corona of Nanoparticles by Clip Photochemistry in Water: Application to the Grafting of RGD Ligands on PEGylated USPIO Imaging Agent.

    Science.gov (United States)

    Pourcelle, Vincent; Laurent, Sophie; Welle, Alexandre; Vriamont, Nicolas; Stanicki, Dimitri; Vander Elst, Luce; Muller, Robert N; Marchand-Brynaert, Jacqueline

    2015-05-20

    The fast development of nanomedicines requires more and more reliable chemical tools in order to accurately design materials and control the surface properties of the nano-objects used in biomedical applications. In this study we describe a smooth and simple photografting technique, i.e., the clip photochemistry, that allows the introduction of molecules of interest in inert polymers or on stealth nanoparticles directly in aqueous solution. First we developed the methodology on polyethylene glycol (PEG) and looked for critical parameters of the process (irradiation times, concentrations, washings) by using several molecular probes and adapted analytical techniques ((19)F qNMR, EA, LSC). We found that the clip photochemistry in water is a robust and efficient method to functionalize PEG. Second we applied it on PEGylated USPIO (USPIO-PEG) magnetic resonance imaging agent and succeeded in introducing RGD peptide and homemade peptidomimetics on their PEG segments. The magnetic abilities of the conjugated nanoparticles were unchanged by the derivatization process as evidenced by their relaxometric properties and their NMRD profile. When tested on Jurkat lymphocyte T Cells, which express αvβ3 integrins, the USPIO conjugated with RGD ligands leads to an increase of the transverse relaxation rate (R2) by a factor 10 to 14 as compared to USPIO-PEG. Consequently, it makes them good candidates for targeted imaging technology in cancer therapy.

  17. Toward realization of 'mix-and-use' approach in ⁶⁸Ga radiopharmacy: preparation, evaluation and preliminary clinical utilization of ⁶⁸Ga-labeled NODAGA-coupled RGD peptide derivative.

    Science.gov (United States)

    Chakraborty, Sudipta; Chakravarty, Rubel; Vatsa, Rakhee; Bhusari, Priya; Sarma, H D; Shukla, Jaya; Mittal, B R; Dash, Ashutosh

    2016-01-01

    The present article demonstrates a 'mix-and-use' approach for radiolabeling RGD peptide derivative with (68)Ga, which is easily adaptable in hospital radiopharmacy practice. The radiotracer thus formulated was successfully used for positron emission tomography (PET) imaging of breast cancer in human patients. The conditions for radiolabeling NODAGA-coupled dimeric cyclic RGD peptide derivative [NODAGA-(RGD)2] with (68)Ga were optimized using (68)Ga obtained from a (68)Ge/(68)Ga generator developed in-house with CeO2-PAN composite sorbent as well as from a commercial (68)Ge/(68)Ga generator obtained from ITG, Germany. Preclinical studies were carried out in C57BL/6 mice bearing melanoma tumors. The radiotracer was prepared in a hospital radiopharmacy using (68)Ga obtained from ITG generator and used for monitoring breast cancer patients by positron emission tomography (PET) imaging. (68)Ga-NODAGA-(RGD)2 could be prepared with high radiolabeling yield (>98%) and specific activity (~50 GBq/μmol) within 10 min at room temperature by mixing (68)Ga with the solution of the peptide conjugate. In vivo biodistribution studies showed significant uptake (5.24±0.39% ID/g) in melanoma tumor at 30 min post-injection, with high tumor-to-background contrast. The integrin αvβ3 specificity of the tracer was corroborated by blocking study. Preliminary clinical studies in locally advanced breast cancer (LABC) patients indicated specifically high tumor uptake (SUVmax 10-15) with good contrast. This is one of the very few reports which presents preliminary clinical data on use of (68)Ga-NODAGA-(RGD)2 and the developed 'mix-and-use' holds tremendous prospect in clinical PET imaging using (68)Ga. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Effects of RGD immobilization on light-induced cell sheet detachment from TiO{sub 2} nanodots films

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kui; Wang, Tiantian [School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027 (China); Yu, Mengliu [The Affiliated Stomatologic Hospital, Zhejiang University, Hangzhou 310003 (China); The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, 310003 (China); Wan, Hongping [School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027 (China); Lin, Jun [The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, 310003 (China); Weng, Wenjian, E-mail: wengwj@zju.edu.cn [School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027 (China); The Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050 (China); Wang, Huiming, E-mail: hmwang1960@hotmail.com [The Affiliated Stomatologic Hospital, Zhejiang University, Hangzhou 310003 (China); The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, 310003 (China)

    2016-06-01

    Light-induced cell detachment is reported to be a safe and effective cell sheet harvest method. In the present study, the effects of arginine–glycine–aspartic acid (RGD) immobilization on cell growth, cell sheet construction and cell harvest through light illumination are investigated. RGD was first immobilized on TiO{sub 2} nanodots films through simple physical adsorption, and then mouse pre-osteoblastic MC3T3-E1 cells were seeded on the films. It was found that RGD immobilization promoted cell adhesion and proliferation. It was also observed that cells cultured on RGD immobilized films showed relatively high level of pan-cadherin. Cells harvested with ultraviolet illumination (365 nm) showed good viability on both RGD immobilized and unmodified TiO{sub 2} nanodot films. Single cell detachment assay showed that cells detached more quickly on RGD immobilized TiO{sub 2} nanodot films. That could be ascribed to the RGD release after UV365 illumination. The current study demonstrated that RGD immobilization could effectively improve both the cellular responses and light-induced cell harvest. - Highlights: • RGD immobilization on TiO{sub 2} nanodots film favors light-induced cell sheet detachment. • Physically adsorbed RGD detaches from the film through ultraviolet illumination. • RGD detachment promotes cells and cell sheets detachment.

  19. Novel Approach to Prepare {sup 99m}Tc-Based Multivalent RGD Peptides

    Energy Technology Data Exchange (ETDEWEB)

    Shuang Liu

    2012-10-24

    This project presents a novel approach to prepare the {sup 99m}Tc-bridged multivalent RGD (arginine-glycine-aspartate) peptides. This project will focus on fundamentals of {sup 99m}Tc radiochemistry. The main objective of this project is to demonstrate the proof-of-principle for the proposed radiotracers. Once a kit formulation is developed for preparation of the {sup 99m}Tc-bridged multivalent RGD peptides, various tumor-bearing animal models will be used to evaluate their potential for SPECT (single photon-emission computed tomography) imaging of cancer. We have demonstrated that (1) multimerization of cyclic RGD peptides enhances the integrin {alpha}{sub v}{beta}{sub 3} bonding affinity and radiotracer tumor uptake; (2) addition of G{sub 3} or PEG{sub 4} linkers makes it possible for two RGD motifs in 3P-RGD{sub 2} and 3G-RGD{sub 2} to achieve simultaneous integrin {alpha}{sub v}{beta}{sub 3} binding; and (3) multimers are actually bivalent (not multivalent), the presence of extra RGD motifs can enhance the tumor retention time of the radiotracer.

  20. Pharmacokinetics, pharmacodynamics, and safety of a platelet GPIIb/IIIa antagonist, RGD891, following intravenous administration in healthy male volunteers.

    Science.gov (United States)

    Zannikos, P N; Rohatagi, S; Jensen, B K; DePhillips, S L; Massignon, D; Calic, F; Sibille, M; Kirkesseli, S

    2000-11-01

    The pharmacokinetics (PK), pharmacodynamics (PD), and safety of a platelet GPIIb/IIIa receptor antagonist, RGD891, and its active metabolite, RGD039, were evaluated after administration of various intravenous regimens of RGD891 to healthy male volunteers in two Phase I studies. Plasma and urine concentrations of RGD891 and RGD039 were measured by validated LC/MS/MS methods with minimum quantifiable limit (MQL) of 1 ng/mL and 10 ng/mL, respectively. PD activity was assessed by percent inhibition of ADP (20 microM)-induced platelet aggregation. Following intravenous dosing, the RGD891 was the predominant compound in plasma. The PK of RGD891 was dose independent associated with modest between-subject variability. RGD891 was rapidly cleared (Cl, 11.2-15.5 L/h), exhibited a restricted distribution (Vss, 23.0-25.9 L) and a short terminal t1/2 lambda z (1.2-2.1 h). Plasma concentrations of the metabolite (RGD039) increased with dose but were variable. RGD039 had longer t1/2 lambda z of 4.5 to 6.6 hours. Renal excretion of unchanged drug played an important role in the elimination of the parent compound. Both RGD891 and RGD039 exhibited renal clearance values that were comparable to the glomerular filtration rate. Intravenous administration of RGD891 effectively inhibited platelet aggregation in a dose-dependent and reversible manner. At the highest dose (60 micrograms/kg bolus dose + 336 micrograms/kg 8-h infusion) > 90% inhibition of platelet aggregation was achieved. PD activity was primarily attributed to the parent compound. Inhibition of platelet aggregation was dependent on the anticoagulant present, with samples containing PPACK showing 20% to 30% lower activity as compared to citrate. RGD891 was safe and well tolerated across the various regimens studies.

  1. Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jianquan; Guo Haixun [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin, E-mail: ymiao@salud.unm.ed [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)

    2010-11-15

    Introduction: The purpose of this study was to examine whether {sup 99m}Tc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone ({alpha}-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and {alpha}{sub v{beta}3} integrin receptors was superior in melanoma targeting to {sup 99m}Tc-labeled {alpha}-MSH or RGD peptide targeting only the MC1 or {alpha}{sub v{beta}3} integrin receptor. Methods: RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were designed to target both MC1 and {alpha}{sub v{beta}3} integrin receptors, MC1 receptor only and {alpha}{sub v{beta}3} integrin receptor only, respectively. The MC1 or {alpha}{sub v{beta}3} integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of {sup 99m}Tc-labeled RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts. Results: RGD-Lys-(Arg{sup 11})CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and {alpha}{sub v{beta}3} integrin receptors, whereas RAD-Lys-(Arg{sup 11})CCMSH or RGD-Lys-(Arg{sup 11})CCMSHscramble lost their {alpha}{sub v{beta}3} integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of {sup 99m}Tc-RAD-Lys-(Arg{sup 11})CCMSH and {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg{sup 11})CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH, whereas the coinjection of RGD+(Arg{sup 11})CCMSH peptide mixture

  2. RGD-conjugated iron oxide magnetic nanoparticles for magnetic resonance imaging contrast enhancement and hyperthermia.

    Science.gov (United States)

    Zheng, S W; Huang, M; Hong, R Y; Deng, S M; Cheng, L F; Gao, B; Badami, D

    2014-03-01

    The purpose of this study was to develop a specific targeting magnetic nanoparticle probe for magnetic resonance imaging and therapy in the form of local hyperthermia. Carboxymethyl dextran-coated ultrasmall superparamagnetic iron oxide nanoparticles with carboxyl groups were coupled to cyclic arginine-glycine-aspartic peptides for integrin α(v)β₃ targeting. The particle size, magnetic properties, heating effect, and stability of the arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide were measured. The arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide demonstrates excellent stability and fast magneto-temperature response. Magnetic resonance imaging signal intensity of Bcap37 cells incubated with arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide was significantly decreased compared with that incubated with plain ultrasmall superparamagnetic iron oxide. The preferential uptake of arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide by target cells was further confirmed by Prussian blue staining and confocal laser scanning microscopy.

  3. Preparation and in vitro evaluation of polymer conjugates actively targeted using RGD-based peptides

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Eliška; Pola, Robert; Pechar, Michal; Janoušková, Olga; Zuska, K.; Etrych, Tomáš

    2017-01-01

    Roč. 6, 4 (Suppl) (2017), s. 91 ISSN 2325-9604. [International Conference and Exhibition on Nanomedicine and Drug Delivery. 29.05.2017-31.05.2017, Osaka] R&D Projects: GA ČR(CZ) GA16-17207S Institutional support: RVO:61389013 Keywords : polymer drug carriers * HPMA * peptide tumor targeting Subject RIV: CD - Macromolecular Chemistry

  4. Conjugal violence

    Directory of Open Access Journals (Sweden)

    Simona Mihaiu

    2015-10-01

    Full Text Available Scientific knowledge of different aspects related to conjugal violence is highly important for people directly involved, such as researchers, practitioners and the entire society. In this respect, globally, specialised studies continue to advance, offer correct definitions, clear descriptions, convincing assessments to certain issues, encouraging thus long-term research, since some specialists have managed to overcome restrictive or ideological methods and explanations. Moreover, in practice, debates reach almost all social, political and legal dimensions regarding appropriate and efficient forms of preventing conjugal violence. Unfortunately, in Romania there are fewer research and prevention approaches of this social problem. In general, attention is directed to domestic violence and conjugal violence is dealt with only implicitly. Considering the given context, the aim of the paper is to outline, by analysing specialised literature, a new research direction and implicitly, social intervention. I specify that this article represents a stage in the ongoing postdoctoral research project, entitled "Conjugal homicide. Aggressors and victims".

  5. NGR-peptide-drug conjugates with dual targeting properties.

    Directory of Open Access Journals (Sweden)

    Kata Nóra Enyedi

    Full Text Available Peptides containing the asparagine-glycine-arginine (NGR motif are recognized by CD13/aminopeptidase N (APN receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integrins provide tumor-homing, which can be exploited for dual targeted delivery of anticancer drugs. We synthesized small cyclic NGR peptide-daunomycin conjugates using NGR peptides of varying stability (c[KNGRE]-NH2, Ac-c[CNGRC]-NH2 and the thioether bond containing c[CH2-CO-NGRC]-NH2, c[CH2-CO-KNGRC]-NH2. The cytotoxic effect of the novel cyclic NGR peptide-Dau conjugates were examined in vitro on CD13 positive HT-1080 (human fibrosarcoma and CD13 negative HT-29 (human colon adenocarcinoma cell lines. Our results confirm the influence of structure on the antitumor activity and dual acting properties of the conjugates. Attachment of the drug through an enzyme-labile spacer to the C-terminus of cyclic NGR peptide resulted in higher antitumor activity on both CD13 positive and negative cells as compared to the branching versions.

  6. Osseous response on linear and cyclic RGD-peptides immobilized on titanium surfaces in vitro and in vivo.

    Science.gov (United States)

    Heller, M; Kumar, V V; Pabst, A; Brieger, J; Al-Nawas, B; Kämmerer, P W

    2018-02-01

    Biomimetic surface modifications of titanium (Ti) implants using the Arg-Gly-Asp-sequence (RGD) are promising to accelerate bone healing in cases of medical implants. Therefore, we compared the impact of linear and cyclic RGD (l- and c-RGD) covalently coupled onto Ti surfaces on the osseous response in vitro and in vivo. In vitro, osteoblasts' behavior on different surfaces (unmodified, amino-silanized [APTES], l- and c-RGD) was analysed regarding adhesion (fluorescence microscopy), proliferation (resazurin stain) and differentiation (reverse transcription polymerase chain reaction on alkaline phosphatase and osteocalcin). In vivo, osteosynthesis screws (unmodified n = 8, l-RGD n = 8, c-RGD n = 8) were inserted into the proximal tibiae of 12 rabbits and evaluated for bone growth parameters (bone implant contact [%] and vertical bone apposition [VBA;%]) at 3 and 6 weeks. In vitro, c- as well as l-RGD surfaces stimulated osteoblasts' adherence, proliferation and differentiation in a similar manner, with only subtle evidence of superiority of the c-RGD modifications. In vivo, c-RGD-modifications led to a significantly increased VBA after 3 and 6 weeks. Thus, coating with c-RGD appears to play an important role influencing osteoblasts' behaviour in vitro but especially in vivo. These findings can be applied prospectively to implantable biomaterials with hypothetically improved survival and success rates. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 106A: 419-427, 2018. © 2017 Wiley Periodicals, Inc.

  7. Sulfonation of Tyrosine as a Method To Improve Biodistribution of Peptide-Based Radiotracers: Novel18F-Labeled Cyclic RGD Analogues.

    Science.gov (United States)

    Haskali, Mohammad B; Denoyer, Delphine; Noonan, Wayne; Culinane, Carleen; Rangger, Christine; Pouliot, Normand; Haubner, Roland; Roselt, Peter D; Hicks, Rodney J; Hutton, Craig A

    2017-04-03

    Control of the biodistribution of radiolabeled peptides has proven to be a major challenge in their application as imaging agents for positron emission tomography (PET). Modification of peptide hydrophilicity in order to increase renal clearance has been a common endeavor to improve overall biodistribution. Herein, we examine the effect of site-specific sulfonation of tyrosine moieties in cyclic(RGDyK) peptides as a means to enhance their hydrophilicity and improve their biodistribution. The novel sulfonated cyclic(RGDyK) peptides were conjugated directly to 4-nitrophenyl 2-[ 18 F]fluoropropionate, and the biodistribution of the radiolabeled peptides was compared with that of their nonsulfonated, clinically relevant counterparts, [ 18 F]GalactoRGD and [ 18 F]FPPRGD2. Site-specific sulfonation of the tyrosine residues was shown to increase hydrophilicity and improve biodistribution of the RGD peptides, despite contributing just 79 Da toward the MW, compared with 189 Da for both the "Galacto" and mini-PEG moieties, suggesting this may be a broadly applicable approach to enhancing biodistribution of radiolabeled peptides.

  8. Angiogenesis Imaging Using (68)Ga-RGD PET/CT: Therapeutic Implications.

    Science.gov (United States)

    Eo, Jae Seon; Jeong, Jae Min

    2016-09-01

    Angiogenesis imaging is important for diagnostic and therapeutic treatment of various malignant and nonmalignant diseases. The Arg-Gly-Asp (RGD) sequence has been known to bind with the αvβ3 integrin that is expressed on the surface of angiogenic blood vessels or tumor cells. Thus, various radiolabeled derivatives of RGD peptides have been developed for angiogenesis imaging. Among the various radionuclides, (68)Ga was the most widely studied for RGD peptide imaging because of its excellent nuclear physical properties, easy-to-label chemical properties, and cost-effectiveness owing to the availability of a (68)Ge-(68)Ga generator. Thus, various (68)Ga-labeled RGD derivatives have been developed and applied for preclinical and clinical studies. Clinical trials were performed for both malignant and nonmalignant diseases. Breast cancer, glioma, and lung cancer were malignant, and myocardial infarction, atherosclerosis, and moyamoya disease were nonmalignant among the investigated diseases. Further, these (68)Ga-labeled RGD derivatives could be applied to assess the effects of antiangiogenic treatment or theragnosis or both, of cancers. In conclusion, the angiogenesis imaging technology using (68)Ga-labeled RGD derivatives might be useful for the development of new therapeutic assessments, and for diagnostic and theragnostic applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. RGD-modified poly(D,L-lactic acid nanoparticles enhance tumor targeting of oridonin

    Directory of Open Access Journals (Sweden)

    Xu J

    2012-01-01

    Full Text Available Jie Xu, Ji-Hui Zhao, Ying Liu, Nian-Ping Feng, Yong-Tai ZhangSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of ChinaObjective: The purpose of this study was to develop an active targeting strategy to improve the therapeutic antitumor efficacy of oridonin (ORI, the main active ingredient in the medicinal herb Rabdosia rubescens.Methods: A modified spontaneous emulsification solvent diffusion method was used to prepare the ORI-loaded atactic poly(D,L-lactic acid nanoparticles (ORI-PLA-NPs. Surface cross-linking with the peptide Arg-Gly-Asp (RGD further modified the ORI-PLA-NPs, generating ORI-PLA-RGD-NPs. The NPs were characterized and release experiments were performed in vitro. The pharmacokinetics, tissue distribution, and antitumor activity of the NPs were studied in mice bearing hepatocarcinoma 22 (H22-derived tumors.Results: The ORI-PLA-NPs and ORI-PLA-RGD-NPs were smooth, sphere-like, and relatively uniform in size. The RGD surface modification slightly increased the mean particle size (95.8 nm for ORI-PLA-NPs versus 105.2 nm for ORI-PLA-RGD-NPs and considerably altered the surface electrical property (-10.19 mV for ORI-PLA-NPs versus -21.95 mV for ORI-PLA-RGD-NPs, but it had no obvious influence on ORI loading (8.23% ± 0.35% for ORI-PLA-NPs versus 8.02% ± 0.38% for ORI-PLA-RGD-NPs, entrapment efficiency (28.86% ± 0.93% for ORI-PLA-NPs versus 28.24% ± 0.81% for ORI-PLA-RGD-NPs, or the release of ORI. The pharmacokinetic properties of free ORI were improved by encapsulation in NPs, as shown by increased area under the concentration-time curve (11.89 ± 0.35 µg·mL-1 · h for ORI solution versus 22.03 ± 0.01 µg · mL-1 · h for ORI-PLA-RGD-NPs and prolonged mean retention time (2.03 ± 0.09 hours for ORI solution versus 8.68 ± 0.66 hours for ORI-PLA-RGD-NPs. In the tissue distribution study, more ORI targeted tumor tissue in the mice treated with ORI-PLA-RGD-NPs than with ORI

  10. Preparation of 177Lu-DOTA/DTPA-Bz-Cys-RGD dimer and biodistribution evaluation in normal mice

    International Nuclear Information System (INIS)

    Sheng Feng; Jia Bing; Wang Fan; He Weiwei; Liu Zhaofei; Zhao Huiyun

    2008-01-01

    177 Lu-DOTA-Bz-Cys-RGD dimer and 177 Lu-DTPA-Bz-Cys-RGD dimer were prepared, and the in vitro and in vivo properties were compared. TLC and HPLC show that the labeling yields of two radiolabeled compounds are more than 95% under optimal conditions (pH=5.0, reacting at 100 degree C for 15-20 min), and the two radiolabeled compounds show pretty good in vitro stability. HPLC analyses and lg P values reveal that lipophilicity of 177 Lu-DOTA-Bz-Cys- RGD dimer is higher than 177 Lu-DTPA-Bz-Cys-RGD dimer. The uptake of 177 Lu-DTPA-Bz-Cys- RGD dimer in other tissues is significantly higher than that of 177 Lu-DOTA-Bz-Cys-RGD dimer at 4 h postinjection, except for blood and spleen. The in vivo stability of 177 Lu-DOTA-Bz-Cys-RGD dimer is much better than 177 Lu-DTPA-Bz-Cys-RGD dimer. Bz-DOTA is an ideal bifunctional chelator for 177 Lu labeling of RGD dimer. (authors)

  11. Cell-adhesive RGD peptide-displaying M13 bacteriophage/PLGA nanofiber matrices for growth of fibroblasts.

    Science.gov (United States)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Oh, Jin-Woo; Kim, Tai Wan; Han, Dong-Wook

    2014-01-01

    M13 bacteriophages can be readily fabricated as nanofibers due to non-toxic bacterial virus with a nanofiber-like shape. In the present study, we prepared hybrid nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 bacteriophages which were genetically modified to display the RGD peptide on their surface (RGD-M13 phage). The surface morphology and chemical composition of hybrid nanofiber matrices were characterized by scanning electron microscopy (SEM) and Raman spectroscopy, respectively. Immunofluorescence staining was conducted to investigate the existence of M13 bacteriophages in RGD-M13 phage/PLGA hybrid nanofibers. In addition, the attachment and proliferation of three different types of fibroblasts on RGD-M13 phage/PLGA nanofiber matrices were evaluated to explore how fibroblasts interact with these matrices. SEM images showed that RGD-M13 phage/PLGA hybrid matrices had the non-woven porous structure, quite similar to that of natural extracellular matrices, having an average fiber diameter of about 190 nm. Immunofluorescence images and Raman spectra revealed that RGD-M13 phages were homogeneously distributed in entire matrices. Moreover, the attachment and proliferation of fibroblasts cultured on RGD-M13 phage/PLGA matrices were significantly enhanced due to enriched RGD moieties on hybrid matrices. These results suggest that RGD-M13 phage/PLGA matrices can be efficiently used as biomimetic scaffolds for tissue engineering applications.

  12. Secretory pathway-dependent localization of the Saccharomyces cerevisiae Rho GTPase-activating protein Rgd1p at growth sites.

    Science.gov (United States)

    Lefèbvre, Fabien; Prouzet-Mauléon, Valérie; Hugues, Michel; Crouzet, Marc; Vieillemard, Aurélie; McCusker, Derek; Thoraval, Didier; Doignon, François

    2012-05-01

    Establishment and maintenance of cell polarity in eukaryotes depends upon the regulation of Rho GTPases. In Saccharomyces cerevisiae, the Rho GTPase activating protein (RhoGAP) Rgd1p stimulates the GTPase activities of Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. Consistent with the distribution of Rho3p and Rho4p, Rgd1p is found mostly in areas of polarized growth during cell cycle progression. Rgd1p was mislocalized in mutants specifically altered for Golgi apparatus-based phosphatidylinositol 4-P [PtdIns(4)P] synthesis and for PtdIns(4,5)P(2) production at the plasma membrane. Analysis of Rgd1p distribution in different membrane-trafficking mutants suggested that Rgd1p was delivered to growth sites via the secretory pathway. Rgd1p may associate with post-Golgi vesicles by binding to PtdIns(4)P and then be transported by secretory vesicles to the plasma membrane. In agreement, we show that Rgd1p coimmunoprecipitated and localized with markers specific to secretory vesicles and cofractionated with a plasma membrane marker. Moreover, in vivo imaging revealed that Rgd1p was transported in an anterograde manner from the mother cell to the daughter cell in a vectoral manner. Our data indicate that secretory vesicles are involved in the delivery of RhoGAP Rgd1p to the bud tip and bud neck.

  13. Evaluation of the therapeutic efficacy and radiotoxicity of the conjugates 177Lu-DOTA-E-c(RGDfK)2 and 177Lu-DOTA-GGC-AuNP-c[RGDfk(C)] in a murine model and their relationship with the inhibition of the angiogenic factors VEGF and HIF-1α

    International Nuclear Information System (INIS)

    Vilchis J, A.

    2013-01-01

    Molecular targeting therapy has become a relevant therapeutic strategy for cancer. The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been proven, and radiolabeled peptides have been demonstrated to be effective in patients with malignant tumors. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of α(v)β(3) integrin, thereby inhibiting angio genesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable m ultimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of 177 Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare with that of 177 Lu-AuNP or 177 Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-micro PET/CT), renal radiotoxicity, renal and tumoral histological characteristics as well as tumoral VEGF and HIF-1? gene expression (by realtime polymerase chain reaction) following treatment with 177 Lu-AuNP-RGD, 177 Lu-AuNP or 177 Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, 177 Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 ± 7.9 Gy) vs other treatments. These results correlated with the observed therapeutic response, in which 177 Lu-AuNP-RGD significantly (p 177 Lu). There was a low uptake in non-target organs and no induction of renal toxicity. 177 Lu-AuNP-RGD demonstrates properties suitable for use as an agent for molecular targeting radiotherapy. (Author)

  14. Development of a new anti-cancer agent for targeted radionuclide therapy: β- radiolabeled RAFT-RGD

    International Nuclear Information System (INIS)

    Petitprin, A.

    2013-01-01

    β-emitters radiolabeled RAFT-RGD as new agents for internal targeted radiotherapy. The αvβ3 integrin is known to play an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. Because of its overexpression on neo-endothelial cells such as those present in growing tumors, as well as on tumor cells of various origins, αvβ3 integrin is an attractive molecular target for diagnosis and therapy of the rapidly growing and metastatic tumors. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin αvβ3 in vitro and in vivo. RAFT-RGD has been used for tumor imaging and drug targeting. This study is the first to evaluate the therapeutic potential of the β-emitters radiolabeled tetrameric RGD peptide RAFT-RGD in a Nude mouse model of αvβ3 -expressing tumors. An injection of 37 MBq of 90 Y-RAFT-RGD or 177 Lu-RAFT-RGD in mice with αvβ3 -positive tumors caused a significant growth delay as compared with mice treated with 37 MBq of 90 Y-RAFT-RAD or 177 Lu-RAFT-RAD or untreated mice. In comparison, an injection of 30 MBq of 90 Y-RAFT-RGD had no efficacy for the treatment of αvβ3 -negative tumors. 90 Y-RAFT-RGD and 177 Lu-RAFT-RGD are potent αvβ3 -expressing tumor targeting agents for internal targeted radiotherapy. (author)

  15. Comparison of biological properties of 99mTc-labeled cyclic RGD Peptide trimer and dimer useful as SPECT radiotracers for tumor imaging

    International Nuclear Information System (INIS)

    Zhao, Zuo-Quan; Yang, Yong; Fang, Wei; Liu, Shuang

    2016-01-01

    Introduction: This study sought to evaluate a 99m Tc-labeled trimeric cyclic RGD peptide ( 99m Tc-4P-RGD 3 ) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of 99m Tc-3P-RGD 2 in the same animal model. Methods: HYNIC-4P-RGD 3 was prepared by reacting 4P-RGD 3 with excess HYNIC-OSu in the presence of diisopropylethylamine. 99m Tc-4P-RGD 3 was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose, 99m Tc-3P-RGD 2 (a α v β 3 -targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the α v β 3 specificity of 99m Tc-4P-RGD 3 . Results: 99m Tc-4P-RGD 3 was prepared with > 95% RCP and high specific activity (~ 200 GBq/μmol). 99m Tc-4P-RGD 3 and 99m Tc-3P-RGD 2 shared almost identical tumor uptake and similar biodistribution properties. 99m Tc-4P-RGD 3 had higher uptake than 99m Tc-3P-RGD 2 in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with 99m Tc-4P-RGD 3 and 99m Tc-3P-RGD 2 . Conclusion: Increasing peptide multiplicity from 3P-RGD 2 to 4P-RGD 3 offers no advantages with respect to the tumor-targeting capability. 99m Tc-4P-RGD 3 is as good a SPECT radiotracer as 99m Tc-3P-RGD 2 for imaging α v β 3 -positive tumors. -- Graphical abstract: This report presents evaluations of a 99m Tc-labeled cyclic RGD peptide trimer ( 99m Tc-4P-RGD 3 ) as the new SPECT radiotracer for tumor imaging. It was found that 99m Tc-4P-RGD 3 was able to accumulate in the xenografted U87MG tumors with high specificity. Display Omitted

  16. Glutathione Conjugation

    Science.gov (United States)

    Shimabukuro, R. H.; Frear, D. S.; Swanson, H. R.; Walsh, W. C.

    1971-01-01

    The primary factor for atrazine selectivity in corn (Zea mays) is the activity of a soluble enzyme, glutathione S-transferase, which detoxifies atrazine by catalyzing the formation of an atrazine-glutathione conjugate (GS-atrazine). The nonenzymatic, benzoxazinone-catalyzed hydrolysis of atrazine to hydroxyatrazine contributed to the total resistance of corn to atrazine, but the nonenzymatic detoxication pathway does not seem to be essential for resistance. All corn lines investigated, except for susceptible GT112, rapidly detoxified atrazine by glutathione conjugation. Only GT112 had low glutathione S-transferase activity. Hydroxyatrazine was found in significant quantities only when atrazine was introduced initially into the roots. The amount of hydroxyatrazine formed was nearly equal for susceptible GT112 and most of the resistant corn lines investigated. This investigation indicates that some plants protect themselves against toxic organic halide compounds with a mechanism similar to that known to exist in animals. PMID:5543779

  17. Roughened titanium surfaces with silane and further RGD peptide modification in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wen-Cheng, E-mail: wencchen@fcu.edu.tw [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, College of Engineering, Feng Chia University, Taichung 40724, Taiwan, ROC (China); Ko, Chia-Ling [School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC (China)

    2013-07-01

    The strategy to achieve osteoregeneration of dental implants during early-stage regeneration is strongly related to surface conditions for achieving highly successful effects after implantation. Surface modifications, namely, mechanical ground, silanization, bonded and sandblasted with pentasequence Gly-Arg-Gly-Asp-Ser (GRGDS) peptide, and acid-etched with Arg-Gly-Asp (RGD) peptide, were compared for their ability to support cell attachment, proliferation, and differentiation on titanium surfaces. The characteristics and comparative in vitro bio-interactions toward osteoprogenitor cells were tested in the four groups with various surface modifications. Compared with the other groups, the sandblasted and acid-etched, and silane with subsequent RGD peptide modified surfaces had the smallest wetting angle, absence of a significant cell viability difference, and largest quantity of alkaline phosphatase production during the expressions of early-stage cell differentiation. The method of synthesizing GRGDS peptides on roughened titanium surfaces has the potential to provide a combination of early bone regeneration and implant of long-term anchored capabilities. Highlights: • The osteoregeneration during early-stage is strongly related to surface conditions. • The wettability with RGD peptide treated surfaces can be enhanced. • Rougher surface binding with RGD peptide can achieve better osseogeneration. • Surfaces with RGD peptide accelerate the progenitor bone cell mineralization.

  18. Neovascularization after ischemic injury: evaluation with {sup 99m}Tc-HYNIC-RGD

    Energy Technology Data Exchange (ETDEWEB)

    Faintuch, Bluma Linkowski; Teodoro, Rodrigo, E-mail: blfaintuch@hotmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Radiopharmacy Center; Oliveira, Erica Aparecida de; Fernandez Nunez, Eutimio Gustavo [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Postgraduation Program; Faintuch, Joel [Universidade de Sao Paulo (USP), SP (Brazil). Medical School. Dept. of Gastroenterology

    2011-01-15

    Purpose: angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of {sup 99m}Tc-HYNIC-{beta}-Ala-RGD. Methods: {sup 99m}Tc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies. Results: the highest ratio between ischemia and control was achieved at the 7th day (2.62 {+-} 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 {+-} 0.23. Scintigraphic image confirmed different uptakes. Conclusion: {sup 99m}Tc-HYNIC-RGD analog concentrated in ischemic tissue by the time of widespread angiogenesis and pertechnetate confirmed reduction in blood flow. In this sense, the protocol can be recommended for ischemic models. (author)

  19. Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

    Science.gov (United States)

    Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2015-10-01

    Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy.

  20. Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with 177Lu for tumors therapy that expressing αβ integrin s

    International Nuclear Information System (INIS)

    Luna G, M. A.

    2014-01-01

    The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of 177 Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of 177 Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential 177 Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain 177 Lu-AuNP-c[RGDfK(C)], the 177 Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. 177 Lu-DOTA-GGC, 177 Lu- DOTA-cRGDfK and 177 Lu-DOTA-E-c(RGDfK) 2 were prepared by adding 177 LuCl 3 (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with 177 Lu-AuNP-c[RGDfK(C)], the MCF7 cell proliferation was significantly inhibited

  1. Preparation of the radiopharmaceutical {sup 99m} Tc-HYNIC-cyclo-Lys-D-Phe-RGD for In vivo image of integrines; Preparacion del radiofarmaco {sup 99m} Tc-HYNIC-ciclo-Lys-D-Phe-RGD para imagen In vivo de integrinas

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez H, E. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

    2007-07-01

    The diagnostic of some pathological processes by means of images constitutes one of the used methods in the determination of the origin, condition and/or evolution of one illness. The use of contrast agents in conjunction with other techniques help to the obtaining and visualization of complex systems, among these we can find to those radiopharmaceuticals used in nuclear medicine to visualize diverse organs and corporal systems. At the moment it is sought to develop a radiopharmaceutical of third generation that can be used for image In vivo of integrines with the purpose of detecting angio genesis processes, that which would allow to diagnose in way it specifies a wide range of primary tumors and their metastasis. Presently work it developed the radiopharmaceutical {sup 99m}Tc-HYNIC-cycle-Lys-D-Phe-RGD, likewise the good conditions were determined for the formation of this complex. The HYNIC was employee as chelating agent, using as co ligands EDDA and Tricine for to complete the sphere of coordination of the {sup 99m}Tc. The conjugated HYNIC-RGD was synthesized, purified, characterized and radiolabelled In situ with {sup 99m}Tc using High pressure liquid chromatography as analysis method in Reverse Phase (RP-HPLC). By this way it was developed the lyophilized formulation for its instantaneous labelled to which were carried out quality control tests. The one conjugated was obtained free of impurities, showing stability at same as their complex formed with {sup 99m}Tc. The analysis method was validated turning out to be necessary, exact, lineal and specific for the quantification of the analyte of interest. The lyophilized formulation showed a radiochemical purity bigger than 95%, besides being sterile and free of pyrogens. The biodistribution tests in athymic mice with induced tumors showed that the radiopharmaceutical was united mainly to the tumor and that this it was excreted mainly for renal via. (Author)

  2. Preparation and evaluation of 177Lu-DOTA-Bz-RGD dimer and 177Lu-DOTA-Bz-PEG4-RGD dimer

    International Nuclear Information System (INIS)

    Shi Jiyun; Jia Bing; Wang Fan; Yu Zilin; Zhao Huiyun

    2007-01-01

    177 Lu-DOTA-Bz-RGD dimer and 177 Lu-DOTA-Bz-PEG4-RGD dimer were pre- pared, and the effect of PEG4 on labeling conditions and in vitro stability as well as pharma-cokinetic properties and biodistribution in normal mice for the radiolebeled compounds was compared. The results of TLC and HPLC show that the labeling yield of two radiolabeled compounds was more than 95% under optimal conditions (pH 4.0 and pH 6.0, respectively, reacting at 100 degree C for 15-20 min). The two radiolabeled compounds show pretty good stability in saline. HPLC analyses and lgP ow values revealed that introducing of PEG4 increased the lipophilic character of radiolabeled compounds, but had no significant changes on pharmacokinetic properties and biodistribution in normal mice. (authors)

  3. The Disease Portals, disease-gene annotation and the RGD disease ontology at the Rat Genome Database.

    Science.gov (United States)

    Hayman, G Thomas; Laulederkind, Stanley J F; Smith, Jennifer R; Wang, Shur-Jen; Petri, Victoria; Nigam, Rajni; Tutaj, Marek; De Pons, Jeff; Dwinell, Melinda R; Shimoyama, Mary

    2016-01-01

    The Rat Genome Database (RGD;http://rgd.mcw.edu/) provides critical datasets and software tools to a diverse community of rat and non-rat researchers worldwide. To meet the needs of the many users whose research is disease oriented, RGD has created a series of Disease Portals and has prioritized its curation efforts on the datasets important to understanding the mechanisms of various diseases. Gene-disease relationships for three species, rat, human and mouse, are annotated to capture biomarkers, genetic associations, molecular mechanisms and therapeutic targets. To generate gene-disease annotations more effectively and in greater detail, RGD initially adopted the MEDIC disease vocabulary from the Comparative Toxicogenomics Database and adapted it for use by expanding this framework with the addition of over 1000 terms to create the RGD Disease Ontology (RDO). The RDO provides the foundation for, at present, 10 comprehensive disease area-related dataset and analysis platforms at RGD, the Disease Portals. Two major disease areas are the focus of data acquisition and curation efforts each year, leading to the release of the related Disease Portals. Collaborative efforts to realize a more robust disease ontology are underway. Database URL:http://rgd.mcw.edu. © The Author(s) 2016. Published by Oxford University Press.

  4. Improved tumor targeting of radiolabeled RGD peptides using rapid dose fractionation.

    NARCIS (Netherlands)

    Janssen, M.; Frielink, C.; Dijkgraaf, I.; Oyen, W.J.G.; Edwards, D.S.; Liu, S.; Rajopadhye, M.; Massuger, L.F.A.G.; Corstens, F.H.M.; Boerman, O.C.

    2004-01-01

    Arginine-glycine-aspartic acid (RGD) peptides preferentially bind to alphavbeta3 integrin, an integrin expressed on newly formed endothelial cells and on various tumor cells. When labeled with beta-emitting radionuclides, these peptides can be used for peptide-receptor radionuclide therapy of

  5. Scanning electron microscopy and swelling test of shrimp shell chitosan and chitosan-RGD scaffolds

    Science.gov (United States)

    Mandacan, M. C.; Yuniastuti, M.; Amir, L. R.; Idrus, E.; Suniarti, D. F.

    2017-08-01

    Shrimp shell chitosan and chitosan-RGD scaffold membranes are produced to be biocompatible with tissue engineering. Nonetheless, their architectural properties have not yet been studied. Analyze the architectural properties of chitosan and chitosan-RGD scaffolds. Analyze pore count and size, interpore distance, and porosity (using SEM testing and ImageJ analysis) and water absorption (using a swelling test). The properties of the chitosan and chitosan-RGD scaffolds were as follows, respectively. The pore counts were 225 and 153; pore size, 171.4 μam and 180.2 μam interpore distance, 105.7 μam and 101.4 μam porosity, 22% and 10.2%; and water absorption, 9.1 mgH2O/mgScaffold and 19.3 mgH2O/mgScaffold. The shrimp shell chitosan-RGD membrane scaffold was found to have architectural properties that make it more conducive to use in tissue engineering.

  6. In Vitro Bioactivity Study of RGD-Coated Titanium Alloy Prothesis for Revision Total Hip Arthroplasty.

    Science.gov (United States)

    Man, Zhentao; Sha, Dan; Sun, Shui; Li, Tao; Li, Bin; Yang, Guang; Zhang, Laibo; Wu, Changshun; Jiang, Peng; Han, Xiaojuan; Li, Wei

    2016-01-01

    Total hip arthroplasty (THA) is a common procedure for the treatment of end-stage hip joint disease, and the demand for revision THA will double by 2026. Ti6Al4V (Titanium, 6% Aluminum, and 4% Vanadium) is a kind of alloy commonly used to make hip prothesis. To promote the osseointegration between the prothesis and host bone is very important for the revision THA. The peptide Arg-Gly-Asp (RGD) could increase cell attachment and has been used in the vascular tissue engineering. In this study, we combined the RGD with Ti6Al4V alloy using the covalent cross-linking method to fabricate the functional Ti6Al4V alloy (FTA). The distribution of RGD oligopeptide on the FTA was even and homogeneous. The FTA scaffolds could promote mouse osteoblasts adhesion and spreading. Furthermore, the result of RT-qPCR indicated that the FTA scaffolds were more beneficial to osteogenesis, which may be due to the improvement of osteoblast adhesion by the RGD oligopeptide coated on FTA. Overall, the FTA scaffolds developed herein pave the road for designing and building more efficient prothesis for osseointegration between the host bone and prothesis in revision THA.

  7. Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically

    Science.gov (United States)

    Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

    2017-02-01

    The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity.

  8. Radiolabeled antibodies and RGD-peptides for the treatment of ovarian cancer.

    NARCIS (Netherlands)

    Janssen, M.L.H.

    2004-01-01

    In this thesis, preclinical studies on new treatment modalities for ovarian cancer are descibed, applying radiolabeled antibodies and radiolabeled RGD-peptides. In chapter 2 a study is described comparing the therapeutic efficacy of the antibody HMFG1 radiolabeled with several beta-emitting

  9. In Vitro Bioactivity Study of RGD-Coated Titanium Alloy Prothesis for Revision Total Hip Arthroplasty

    Directory of Open Access Journals (Sweden)

    Zhentao Man

    2016-01-01

    Full Text Available Total hip arthroplasty (THA is a common procedure for the treatment of end-stage hip joint disease, and the demand for revision THA will double by 2026. Ti6Al4V (Titanium, 6% Aluminum, and 4% Vanadium is a kind of alloy commonly used to make hip prothesis. To promote the osseointegration between the prothesis and host bone is very important for the revision THA. The peptide Arg-Gly-Asp (RGD could increase cell attachment and has been used in the vascular tissue engineering. In this study, we combined the RGD with Ti6Al4V alloy using the covalent cross-linking method to fabricate the functional Ti6Al4V alloy (FTA. The distribution of RGD oligopeptide on the FTA was even and homogeneous. The FTA scaffolds could promote mouse osteoblasts adhesion and spreading. Furthermore, the result of RT-qPCR indicated that the FTA scaffolds were more beneficial to osteogenesis, which may be due to the improvement of osteoblast adhesion by the RGD oligopeptide coated on FTA. Overall, the FTA scaffolds developed herein pave the road for designing and building more efficient prothesis for osseointegration between the host bone and prothesis in revision THA.

  10. Rat Strain Ontology: structured controlled vocabulary designed to facilitate access to strain data at RGD.

    Science.gov (United States)

    Nigam, Rajni; Munzenmaier, Diane H; Worthey, Elizabeth A; Dwinell, Melinda R; Shimoyama, Mary; Jacob, Howard J

    2013-11-22

    The Rat Genome Database (RGD) ( http://rgd.mcw.edu/) is the premier site for comprehensive data on the different strains of the laboratory rat (Rattus norvegicus). The strain data are collected from various publications, direct submissions from individual researchers, and rat providers worldwide. Rat strain, substrain designation and nomenclature follow the Guidelines for Nomenclature of Mouse and Rat Strains, instituted by the International Committee on Standardized Genetic Nomenclature for Mice. While symbols and names aid in identifying strains correctly, the flat nature of this information prohibits easy search and retrieval, as well as other data mining functions. In order to improve these functionalities, particularly in ontology-based tools, the Rat Strain Ontology (RS) was developed. The Rat Strain Ontology (RS) reflects the breeding history, parental background, and genetic manipulation of rat strains. This controlled vocabulary organizes strains by type: inbred, outbred, chromosome altered, congenic, mutant and so on. In addition, under the chromosome altered category, strains are organized by chromosome, and further by type of manipulations, such as mutant or congenic. This allows users to easily retrieve strains of interest with modifications in specific genomic regions. The ontology was developed using the Open Biological and Biomedical Ontology (OBO) file format, and is organized on the Directed Acyclic Graph (DAG) structure. Rat Strain Ontology IDs are included as part of the strain report (RS: ######). As rat researchers are often unaware of the number of substrains or altered strains within a breeding line, this vocabulary now provides an easy way to retrieve all substrains and accompanying information. Its usefulness is particularly evident in tools such as the PhenoMiner at RGD, where users can now easily retrieve phenotype measurement data for related strains, strains with similar backgrounds or those with similar introgressed regions. This

  11. Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with {sup 177}Lu for tumors therapy that expressing αβ integrin s; Sistema monomerico, dimerico y multimerico de peptidos de RGD radiomarcados con {sup 177}Lu para terapia de tumores que expresan integrinas αβ

    Energy Technology Data Exchange (ETDEWEB)

    Luna G, M. A.

    2014-07-01

    The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of {sup 177}Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of {sup 177}Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential {sup 177}Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain {sup 177}Lu-AuNP-c[RGDfK(C)], the {sup 177}Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. {sup 177}Lu-DOTA-GGC, {sup 177}Lu- DOTA-cRGDfK and {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} were prepared by adding {sup 177}LuCl{sub 3} (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with {sup 177}Lu

  12. Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD.

    Science.gov (United States)

    Balasundaram, Ganesan; Sato, Michiko; Webster, Thomas J

    2006-05-01

    Better materials are needed to promote bone growth. For this reason, the present study created nanometer crystalline hydroxyapatite (HA) and amorphous calcium phosphate compacts functionalized with the arginine-glycine-aspartic acid (RGD) peptide sequence. Crystalline HA and amorphous calcium phosphate nanoparticles were synthesized by a wet chemical process followed by a hydrothermal treatment for 2 h at 200 degrees C and 70 degrees C, respectively. Resulting particles were then pressed into compacts. For the preparation of conventional HA particles (or those with micron diameters), the aforementioned pressed compacts were sintered at 1,100 degrees C for 2 h. Peptide functionalization was conducted by means of a three step reaction procedure: silanization with 3-aminopropyltriethoxysilane (APTES), cross-linking with N-succinimidyl-3-maleimido propionate (SMP), and finally peptide immobilization. The three step reaction procedure was characterized by a novel 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) fluorescence technique. For all materials, results showed that the immobilization of the cell adhesive RGD sequence increased osteoblast (bone-forming cell) adhesion compared to those non-functionalized and those functionalized with the noncell adhesive control peptide (RGE) after 4 h. However, surprisingly, results also showed that the adhesion of osteoblasts on non-functionalized amorphous nanoparticulate calcium phosphate was similar to conventional HA functionalized with RGD. Osteoblast adhesion on nanocrystalline HA (unfunctionalized and functionalized with RGD) was below that of the respective functionalized amorphous calcium phosphate but above that of the respective functionalized conventional HA. In this manner, results of this study suggest that decreasing the particulate size into the nanometer regime and reducing crystallinity of calcium phosphate based materials may promote osteoblast adhesion to the same degree as the well

  13. Fluorescent and quantitative mitochondrial redox imaging of tumor targeted by Octa-RGD probe

    Directory of Open Access Journals (Sweden)

    Shuang Sha

    2016-07-01

    Full Text Available Integrins, over-expressed in a broad range of cancer diseases, are widely utilized as a tumor biomarker. Metabolism investigation also plays important roles in tumor theranostics. Developing simple integrin-targetting probe and monitoring tumor metabolism will give opportunities to find ways for cancer treatment, however, the investigation of tumor metabolism with integrin receptor based probes has been rarely reported so far. Here, we developed an octavalent fluorescent probe Octa-RGD by convenient genetic method, based on one tetrameric far-red fluorescent protein (fRFP linked with RGD peptides. We validated its intergin targeting by confocal imaging in vitro. Then we screened a variety of tumor cells, and differentiated their binding affinity based on the fluorescence of the probe via flow cytometry. Among these cells, CNE-2 cells had the highest uptake of the probe, while B16 cells had the lowest, corresponding with their intergin expression levels. Next, the fluorescent and metabolic imaging was performed in HT1080 (intergin postive tumor, where nicotinamide adenine dinucleotide hydrogen (NADH, flavoprotein (Fp and fRFP fluorescent signals were collected. The tumor from mice intravenously injected with Octa-RGD probe displayed obviously higher NADH redox ratio NADH/(Fp+NADH and fRFP signal, than those with fRFP protein. It suggested that integrin targeting may have influence on the target cell metabolism, and further demonstrated Octa-RGD probe facilitated its uptake in the targeted tumor in vivo. This paper developed a useful probe, which can bind integrins specifically and efficiently in tumor cells, and together with tumor metabolic information, it may provide new insight for RGD targeting-based cancer therapeutics.

  14. Molecular imaging-guided photothermal/photodynamic therapy against tumor by iRGD-modified indocyanine green nanoparticles.

    Science.gov (United States)

    Yan, Fei; Wu, Hao; Liu, Hongmei; Deng, Zhiting; Liu, Hong; Duan, Wanlu; Liu, Xin; Zheng, Hairong

    2016-02-28

    Multifunctional near-infrared (NIR) nanoparticles demonstrate great potential in tumor theranostic applications. To achieve the sensitive detection and effective phototherapy in the early stage of tumor genesis, it is highly desirable to improve the targeting of NIR theranostic agents to biomarkers and to enhance their accumulation in tumor. Here we report a novel targeted multifunctional theranostic nanoparticle, internalized RGD (iRGD)-modified indocyanine green (ICG) liposomes (iRGD-ICG-LPs), for molecular imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) therapy against breast tumor. The iRGD peptides with high affinity to αvβ3 integrin and effective tumor-internalized property were firstly used to synthesize iRGD-PEG2000-DSPE lipopeptides, which were further utilized to fabricate the targeted ICG liposomes. The results indicated that iRGD-ICG-LPs exhibited excellent stability and could provide an accurate and sensitive detection of breast tumor through NIR fluorescence molecular imaging. We further employed this nanoparticle for tumor theranostic application, demonstrating significantly higher tumor accumulation and tumor inhibition efficacy through PTT/PDT effects. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of iRGD-ICG-LPs over non-targeted ICG-LPs. Notably, the targeting therapy mediated by iRGD provides almost equivalent anti-tumor efficacy at a 12.5-fold lower drug dose than that by monoclonal antibody, and no tumor recurrence and obvious treatment-induced toxicity were observed in our study. Our study provides a promising strategy to realize the sensitive detection and effective treatment of tumors by integrating molecular imaging into PTT/PDT therapy. Copyright © 2015. Published by Elsevier B.V.

  15. Graphene oxide-stimulated myogenic differentiation of C2C12 cells on PLGA/RGD peptide nanofiber matrices

    Science.gov (United States)

    Shin, Y. C.; Lee, J. H.; Kim, M. J.; Hong, S. W.; Oh, J.-W.; Kim, C.-S.; Kim, B.; Hyun, J. K.; Kim, Y.-J.; Han, D.-W.

    2015-07-01

    During the last decade, much attention has been paid to graphene-based nanomaterials because they are considered as potential candidates for biomedical applications such as scaffolds for tissue engineering and substrates for the differentiation of stem cells. Until now, electrospun matrices composed of various biodegradable copolymers have been extensively developed for tissue engineering and regeneration; however, their use in combination with graphene oxide (GO) is novel and challenging. In this study, nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 phage with RGD peptide displayed on its surface (RGD peptide-M13 phage) were prepared as extracellular matrix (ECM)-mimicking substrates. RGD peptide is a tripeptide (Arg-Gly-Asp) found on ECM proteins that promotes various cellular behaviors. The physicochemical properties of PLGA and RGD peptide-M13 phage (PLGA/RGD peptide) nanofiber matrices were characterized by atomic force microscopy, Fourier-transform infrared spectroscopy and thermogravimetric analysis. In addition, the growth of C2C12 mouse myoblasts on the PLGA/RGD peptide matrices was examined by measuring the metabolic activity. Moreover, the differentiation of C2C12 mouse myoblasts on the matrices when treated with GO was evaluated. The cellular behaviors, including growth and differentiation of C2C12 mouse myoblasts, were substantially enhanced on the PLGA/RGD peptide nanofiber matrices when treated with GO. Overall, these findings suggest that the PLGA/RGD peptide nanofiber matrices can be used in combination with GO as a novel strategy for skeletal tissue regeneration.

  16. 124I labeled Arg-Gly-Asp (RGD) peptide: PET/MR fusion imaging of tumor expressing integrin v3

    International Nuclear Information System (INIS)

    Yun, Seon Young; Park, Jeong Chan; Chen, Xiaoyuan

    2007-01-01

    Tumor-induced angiogenesis and metastasis express high level of integrin v3 which has become a promising diagnostic biomarker and therapeutic target for various tumors. Radiolabeled RGD (Arg-Gly-Asp) peptides are well known to specifically bind to integrin and can be used not only for noninvasive imaging of integrin over-expression but also for integrin-targeted radionuclide therapy. We used three RGDyK derivatives, monomeric-, dimeric- and tetrameric-RGD for radio labeling. They were labeled with [ 124 I]NaI using iodo-bead. Labeled RGD peptide was purified by FPLC. Xenografts were induced by subcutaneous injection of 1X10 7 U87MG cells into the right thigh of female Balb/c nude mice. After injection of 124 I-labeled monomeric-RGD via the tail vein, the microPET imaging was obtained during 2 hours. Right after microPET imaging, T 2 -weighted MR imaging was performed with fast gradient spin echo sequence in 0.8 mm of a slice thickness. PET/MR fusion images were constructed by AMIDE program. For immobilization and reproducible positioning of animal, animal-specific positioning molds were fabricated. Monomeric-RGD peptide was labeled with 124 I in labeling yield of 50%. After FPLC purification, the radiochemical purity was above 90%. U87MG tumor was clearly seen in both microPET and MR imaging of tumor-bearing nude mouse. The fusion imaging was well constructed by using AMIDE with little discrepancy thanks to animal-specific molds. Three RGD derivatives were also labeled with 131 I in labeling yield of 20-55%. All three RGD peptides were successfully radioiodinated with 124 I or 131 I. U87MG glioblastoma tumor was clearly visualized in PET/MR fusion imaging. MicroPET/MR fusion imaging of dimeric- and tetrameric-RGD peptides in tumor bearing mice will also be presented during conference

  17. Tat PTD-Endostatin-RGD: A novel protein with anti-angiogenesis effect in retina via eye drops.

    Science.gov (United States)

    Li, Yan; Li, Lian; Li, Zhiwei; Sheng, Juzheng; Zhang, Xinke; Feng, Danyang; Zhang, Xu; Yin, Fengxin; Wang, Aijun; Wang, Fengshan

    2016-10-01

    Diabetic retinopathy is a leading cause of blindness. The objective was to design a novel fusion protein, Tat PTD-Endostatin-RGD, to treat retinal neovascularization via eye drops instead of traditional intravitreal injection trepapeutical methods. The anti-angiogenesis ability was evaluated in vitro by chick embryo chorioallantoic membrane assay, wound healing assay and tube formation assay. Corneal barrier and blood-retina barrier were constructed in vitro to investigate the penetration ability of Tat PTD-Endostatin-RGD. Western blot was used to detect the integrin αvβ3 expression level in rat retina microvascular endothelial cells which was stimulated by S-nitroso-N-acetylpenicillamine. The binding affinity of Tat PTD-Endostatin-RGD to integrin αvβ3 was investigated by evaluating the penetration ability on blood-retina barriers treated with S-nitroso-N-acetylpenicillamine. The pharmacodynamics and efficacy analysis were further carried out in the oxygen-induced retinopathy model in vivo. In addition, the pharmacokinetic profile via eye drops was studied on a C57BL/6 mice model. Tat PTD-Endostatin-RGD showed high anti-angiogenesis activity and high ability to penetrate these two barriers in vitro. The Western blot results indicated S-nitroso-N-acetylpenicillamine upregulated the expression level of integrin αvβ3 in a dose-dependent manner. Tat PTD-Endostatin-RGD showed a high affinity to rat retina microvascular endothelial cells treated with S-nitroso-N-acetylpenicillamine. The results showed that Tat PTD-Endostatin-RGD could inhibit abnormal angiogenesis in retina via eye drops. Tat PTD-Endostatin-RGD showed high penetration ability through ocular barriers, bound specifically to integrin αvβ3 and effectively inhibited the abnormal angiogenesis. Tat PTD-Endostatin-RGD represents a potent novel drug applied via eye drops for fundus oculi neovascularization diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Cell-adhesive RGD peptide-displaying M13 bacteriophage/PLGA nanofiber matrices for growth of fibroblasts

    OpenAIRE

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Oh, Jin-Woo; Kim, Tai Wan; Han, Dong-Wook

    2014-01-01

    Background M13 bacteriophages can be readily fabricated as nanofibers due to non-toxic bacterial virus with a nanofiber-like shape. In the present study, we prepared hybrid nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 bacteriophages which were genetically modified to display the RGD peptide on their surface (RGD-M13 phage). Results The surface morphology and chemical composition of hybrid nanofiber matrices were characterized by scanning electron microscopy (SEM)...

  19. Enhanced {sup 18}F-FDG uptake in activated neutrophils is unaffected by respiratory burst inhibition with RGD

    Energy Technology Data Exchange (ETDEWEB)

    Paik, J. Y.; Lee, K. H.; Go, B. H.; Jeong, K. H.; Kim, H. K.; Choi, J. S.; Choi, Y.; Kim, P. T [Samsung Medical Center, Seoul (Korea, Republic of)

    2004-07-01

    Respiratory burst generation is an important response of activated neutrophils and is associated with enhanced glucose metabolism. Since such activation in dependent on adhesion through integrins, we investigated how integrin occupation with RGD influences respiratory burst response and {sup 18}F-FDG uptake in neutrophils. Human neutrophils separated from healthy volunteers were incubated in RPMI media. For RGD peptide inhibitory experiments, neutrophils were preincubated with 200 {mu} g/ml of cRGD peptides ad 37.deg. for 2 hr prior. Respiratory burst generation and uptake of {sup 18}F-FDG was then measured with or without PMA stimulation. Cellular total hexokinase levels were assayed with a colorimetric method. Treatment with RGD in the basal state resulted in a significant but relatively small increase in neutrophil superoxide release to 1.5{+-}0.25 fold o control levels (p<0.005). Whereas PMA stimulation caused a marked increase in superoxide generation, pretreatment with RGD caused a significant attenuation of this response to 35.6{+-}0.2% (p<0.005). PMA stimulation resulted in a significant increase in {sup 18}F-FDG uptake. However, unlike the attenution of superoxide generation, neutrophils pretreated with RGD before PMA stimulation showed an identical magnitude of enhanced {sup 18}F-FDG uptake (201.8{+-}20.5 of controls, p=0.0001). In addition, hexokinase levels were increased to comparable levels of approximately 1.5 fold for PMA stimulated neutrophils irrespective of RGD pretreatment. In conclusion, soluble RGD blocks stimulation of respiratory burst activation in neutrophils but does not inhibit stimulation of cellular glucose metabolism. This dissociation may contribute to maximally enhanced neutrophil FDG uptake in inflammatory lesions regardless of the occupancy of their integrin receptors.

  20. Mechanisms of cell penetration and cytotoxicity of ultrasmall Au nanoparticles conjugated to doxorubicin and/or targeting peptides

    Science.gov (United States)

    Nadeau, Jay; Poon, Wilson; Zhang, Xuan

    2015-03-01

    The goals of this work were to determine whether conjugation of any of four selected peptides to Au nanoparticles improved their delivery to B16 melanoma in vitro and in vivo. In in vitro cytotoxicity assays, peptides and conjugates were endocytosed but did not escape from endosomes. None of the peptides showed any cytotoxicity, with or without conjugation to the nanoparticles. The combination of peptides and doxorubicin did not improve upon the cytotoxicity of gold-doxorubicin alone. We then tested targeting in vivo using inductively coupled plasma mass spectrometry to quantify the concentration of Au in the organs of B16 tumor-bearing mice 4, 24, and 72 h after intravenous Au nanoparticle injection. These experiments showed that in some cases, peptide conjugation improved upon the enhanced permeability and retention (EPR) effect. A peptide based upon the myxoma virus and the cyclic RGD peptide were both effective at tumor targeting; myxoma was more effective with un-PEGylated particles, and cRGD with PEGylated particles. The FREG and melanocyte stimulating hormone (MSH) peptides did not improve targeting. These results suggest that these peptides may improve delivery of Au particles to tumors, but also may prevent entry of particles into cell nuclei.

  1. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    International Nuclear Information System (INIS)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang Seok; Hong, Suck Won; Han, Dong Wook; Kim, Chun Tae; Oh, Jin Woo

    2015-01-01

    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic-co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

  2. The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is mediated by tumor-specific immunity.

    Directory of Open Access Journals (Sweden)

    Anne Kleijn

    Full Text Available The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy.

  3. RGD Peptide-Grafted Graphene Oxide as a New Biomimetic Nano interface for Impedance-Monitoring Cell Behaviors

    International Nuclear Information System (INIS)

    Li, J.; Zheng, L.; Zeng, L.; Zhang, Y.; Jiang, L.; Song, J.; Li, J.; Zheng, L.; Song, J.; Li, J.; Zheng, L.; Song, J.

    2016-01-01

    A new biomimetic nano interface was constructed by facile grafting the bioactive arginylglycylaspartic acid (RGD) peptide on the graphene oxide (GO) surface through carbodiimide and N-hydroxysuccinimide coupling amidation reaction. The formed RGD-GO nano composites own unique two-dimensional structure and desirable electrochemical performance. The linked RGD peptides could improve GO∼s biocompatibility and support the adhesion and proliferation of human periodontal ligament fibroblasts (HPLFs) on RGD-GO biofilm surface. Furthermore the biologically active RGD-GO nano composites were demonstrated as a potential biomimetic nano interface for monitoring cell bio behaviors by electrochemical impedance spectroscopy (EIS). By analysis of the data obtained from equivalent circuit-fitting impedance spectroscopy, the information related to cell membrane capacitance, cell-cell gap resistance, and cell-electrode interface gap resistance in the process of cell adhesion and proliferation could be obtained. Besides, this proposed impedance-based cell sensor could be used to assess the inhibition effect of the lipopolysaccharide (LPS) on the HPLFs proliferation. Findings from this work suggested that RGD peptide functionalized GO nano materials may be not only applied in dental tissue engineering but also used as a sensor interface for electrochemical detection and analysis of cell behaviors in vitro.

  4. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang Seok; Hong, Suck Won; Han, Dong Wook; Kim, Chun Tae; Oh, Jin Woo [Pusan National University, Busan (Korea, Republic of)

    2015-01-15

    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic-co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

  5. An iRGD Based Strategy to Study Electrochemically the Species Inside a Cell

    Directory of Open Access Journals (Sweden)

    Genxi Li

    2012-08-01

    Full Text Available This paper reports a method for electrical communication between the inner part of cells and an electrode with the help of iRGD peptide. Due to the enhancement of the cell penetration caused by iRGD peptide, DNA molecules, previously modified on a gold electrode surface, can be easily transfected into the cells. At the same time, doxorubicin, an anticancer drug, can also be transfected into cells with high penetration. Consequently, doxorubicin binds to DNA chains through electrostatic interaction, and the redox reaction is transferred out of the cell across the cell membrane. As a result, this work may provide a novel way to get information from inside of cells.

  6. The Adenovirus Type 3 Dodecahedron's RGD Loop Comprises an HSPG Binding Site That Influences Integrin Binding

    Directory of Open Access Journals (Sweden)

    E. Gout

    2010-01-01

    Full Text Available Human type 3 adenovirus dodecahedron (a virus like particle made of twelve penton bases features the ability to enter cells through Heparan Sulphate Proteoglycans (HSPGs and integrins interaction and is used as a versatile vector to deliver DNA or proteins. Cryo-EM reconstruction of the pseudoviral particle with Heparan Sulphate (HS oligosaccharide shows an extradensity on the RGD loop. A set of mutants was designed to study the respective roles of the RGD sequence (RGE mutant and of a basic sequence located just downstream. Results showed that the RGE mutant binding to the HS deficient CHO-2241 cells was abolished and unexpectedly, mutation of the basic sequence (KQKR to AQAS dramatically decreased integrin recognition by the viral pseudoparticle. This basic sequence is thus involved in integrin docking, showing a close interplay between HSPGs and integrin receptors.

  7. Bio-compatibility of ion beam-modified and RGD-grafted polyethylene

    Czech Academy of Sciences Publication Activity Database

    Ročková-Hlaváčková, K.; Švorčík, V.; Bačáková, Lucie; Dvořánková, B.; Heitz, J.; Hnatowicz, Vladimír

    2004-01-01

    Roč. 225, č. 3 (2004), s. 275-282 ISSN 0168-583X R&D Projects: GA AV ČR IAA5011301; GA ČR GA106/03/0514 Grant - others:CZ-AT(CZ) Aktion 2002-7 Institutional research plan: CEZ:AV0Z5011922 Keywords : modified polyethylene * ion beam * RGD grafting Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.997, year: 2004

  8. Segmented conjugated polymers

    Indian Academy of Sciences (India)

    Segmented conjugated polymers, wherein the conjugation is randomly truncated by varying lengths of non-conjugated segments, form an interesting class of polymers as they not only represent systems of varying stiffness, but also ones where the backbone can be construed as being made up of chromophores of varying ...

  9. Locally-Delivered T-Cell-Derived Cellular Vehicles Efficiently Track and Deliver Adenovirus Delta24-RGD to Infiltrating Glioma

    Directory of Open Access Journals (Sweden)

    Rutger K. Balvers

    2014-08-01

    Full Text Available Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs, which can be targeted towards the tumor microenvironment. Here, we studied T-cells, often having a natural capacity to target tumors, for their feasibility as a CV to deliver the oncolytic adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in co-culture with the glioblastoma stem cell (GSC line, MGG8, for the optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail vein injections on intratumoral virus distribution and overall survival was addressed in an orthotopic glioma stem cell (GSC-based xenograft model. Jurkat T-cells were demonstrated to facilitate the amplification and transfer of Delta24-RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T-cells into the brains of GSC-bearing mice led to migration towards the tumor and dispersion of the virus within the tumor core and infiltrative zones. This occurred after injection into the ipsilateral hemisphere, as well as into the non-tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD led to the inhibition of tumor growth compared to non-treated controls, resulting in prolonged survival (p = 0.007. Systemic administration of virus-loaded T-cells resulted in intratumoral viral delivery, albeit at low levels. Based on these findings, we conclude that T-cell-based CVs are a feasible approach to local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting requires further improvement.

  10. Fetal muscle gene transfer is not enhanced by an RGD capsid modification to high-capacity adenoviral vectors.

    Science.gov (United States)

    Bilbao, R; Reay, D P; Hughes, T; Biermann, V; Volpers, C; Goldberg, L; Bergelson, J; Kochanek, S; Clemens, P R

    2003-10-01

    High levels of alpha(v) integrin expression by fetal muscle suggested that vector re-targeting to integrins could enhance adenoviral vector-mediated transduction, thereby increasing safety and efficacy of muscle gene transfer in utero. High-capacity adenoviral (HC-Ad) vectors modified by an Arg-Gly-Asp (RGD) peptide motif in the HI loop of the adenoviral fiber (RGD-HC-Ad) have demonstrated efficient gene transfer through binding to alpha(v) integrins. To test integrin targeting of HC-Ad vectors for fetal muscle gene transfer, we compared unmodified and RGD-modified HC-Ad vectors. In vivo, unmodified HC-Ad vector transduced fetal mouse muscle with four-fold higher efficiency compared to RGD-HC-Ad vector. Confirming that the difference was due to muscle cell autonomous factors and not mechanical barriers, transduction of primary myogenic cells isolated from murine fetal muscle in vitro demonstrated a three-fold better transduction by HC-Ad vector than by RGD-HC-Ad vector. We hypothesized that the high expression level of coxsackievirus and adenovirus receptor (CAR), demonstrated in fetal muscle cells both in vitro and in vivo, was the crucial variable influencing the relative transduction efficiencies of HC-Ad and RGD-HC-Ad vectors. To explore this further, we studied transduction by HC-Ad and RGD-HC-Ad vectors in paired cell lines that expressed alpha(v) integrins and differed only by the presence or absence of CAR expression. The results increase our understanding of factors that will be important for retargeting HC-Ad vectors to enhance gene transfer to fetal muscle.

  11. Effect of amino acids near the RGD sequence on binding activities between αIIbβ3 integrin and fibrinogen in the presence of RGD-containing synthetic peptides from elegantin and angustatin.

    Science.gov (United States)

    Oyama, Etsuko; Takahashi, Hidenobu; Ishii, Kazuyuki

    2017-10-01

    Elegantin and angustatin, which were isolated from the snake venoms of Protobothrops elegans and Dendroaspis angusticeps, markedly inhibit binding between platelet integrins and fibrinogen via the Arg-Gly-Asp (RGD) sequence. Angustatin, which is a three-finger toxin containing the RGD sequence, inhibits platelet aggregation almost ten times more strongly than disintegrin isolated from the venoms of Viperidae and Crotalidae. The RGD sequences of both polypeptides are located at the top of hairpin loops, and the composition of the RGD loop is very important for binding to integrin. We investigated the effects of synthetic RGD loop peptides from angustatin and elegantin on ADP- or collagen-induced platelet aggregation and αIIbβ3-fibrinogen binding. Synthetic angustatin (PRGDMP)-type peptides inhibited platelet aggregation more strongly than elegantin (ARGDDX)-type peptides. In particular, the cyclic angustatin peptide (CPRGDMPC) inhibited ADP- and collagen-induced platelet aggregation at least 10-50 times more strongly than the other peptides. The cyclic angustatin peptide (CPRGDMPC) was also the strongest inhibitor of binding between αIIbβ3 and fibrinogen, the IC 50 of this peptide was approximately 2.58μM. Regarding the inhibition of binding between αIIbβ3 and fibrinogen, CPRGDMPC demonstrated a stronger inhibitory and more stable effect in the presence of Mg 2+ than in the presence of Ca 2+ . Copyright © 2017 Elsevier Inc. All rights reserved.

  12. RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice.

    Science.gov (United States)

    Jahanban-Esfahlan, Rana; Seidi, Khaled; Monhemi, Hassan; Adli, Amir Daei Farshchi; Minofar, Babak; Zare, Peyman; Farajzadeh, Davoud; Farajnia, Safar; Behzadi, Ramezan; Abbasi, Mehran Mesgari; Zarghami, Nosratollah; Javaheri, Tahereh

    2017-08-15

    Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any significant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and afforded favorable interaction of fusion proteins with prothrombin and α v β 3 endothelial cell receptors, as verified by in silico, in vitro, and in vivo experiments. Although free coagulase elicited robust coagulase activity in vitro, only targeted coagulase (tCoa-RGD) was capable of producing extensive thrombosis, and subsequent infarction and massive necrosis of CT26 mouse colon, 4T1 mouse mammary and SKOV3 human ovarian tumors in mice. Additionally, systemic injections of lower doses of tCoa-RGD produced striking tumor growth inhibition of CT26, 4T1 and SKOV3 solid tumors in animals. Altogether, the nontoxic nature, unique shortcut mechanism, minimal effective dose, wide therapeutic window, efficient induction of thrombosis, local effects and susceptibility of human blood to coagulase suggest tCoa-RGD fusion proteins as a novel and promising anticancer therapy for human trials.

  13. cRGD-installed docetaxel-loaded mertansine prodrug micelles: redox-triggered ratiometric dual drug release and targeted synergistic treatment of B16F10 melanoma

    Science.gov (United States)

    Zhong, Ping; Qiu, Min; Zhang, Jian; Sun, Huanli; Cheng, Ru; Deng, Chao; Meng, Fenghua; Zhong, Zhiyuan

    2017-07-01

    Combinatorial chemotherapy, which has emerged as a promising treatment modality for intractable cancers, is challenged by a lack of tumor-targeting, robust and ratiometric dual drug release systems. Here, docetaxel-loaded cRGD peptide-decorated redox-activable micellar mertansine prodrug (DTX-cRGD-MMP) was developed for targeted and synergistic treatment of B16F10 melanoma-bearing C57BL/6 mice. DTX-cRGD-MMP exhibited a small size of ca. 49 nm, high DTX and DM1 loading, low drug leakage under physiological conditions, with rapid release of both DTX and DM1 under a cytoplasmic reductive environment. Notably, MTT and flow cytometry assays showed that DTX-cRGD-MMP brought about a synergistic antitumor effect to B16F10 cancer cells, with a combination index of 0.37 and an IC50 over 3- and 13-fold lower than cRGD-MMP (w/o DTX) and DTX-cRGD-Ms (w/o DM1) controls, respectively. In vivo studies revealed that DTX-cRGD-MMP had a long circulation time and a markedly improved accumulation in the B16F10 tumor compared with the non-targeting DTX-MMP control (9.15 versus 3.13% ID/g at 12 h post-injection). Interestingly, mice treated with DTX-cRGD-MMP showed almost complete growth inhibition of B16F10 melanoma, with tumor inhibition efficacy following an order of DTX-cRGD-MMP > DTX-MMP (w/o cRGD) > cRGD-MMP (w/o DTX) > DTX-cRGD-Ms (w/o DM1) > free DTX. Consequently, DTX-cRGD-MMP significantly improved the survival rates of B16F10 melanoma-bearing mice. Importantly, DTX-cRGD-MMP caused little adverse effects as revealed by mice body weights and histological analyses. The combination of two mitotic inhibitors, DTX and DM1, appears to be an interesting approach for effective cancer therapy.

  14. 68Ga- and 111In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

    International Nuclear Information System (INIS)

    Decristoforo, Clemens; Hernandez Gonzalez, Ignacio; Rupprich, Marco; Virgolini, Irene; Carlsen, Janette; Huisman, Marc; Wester, Hans-Juergen; Haubner, Roland

    2008-01-01

    αvβ3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [ 18 F]Galacto-RGD that monitoring of αvβ3 expression is feasible. Here, we introduce 68 Ga- and 111 In-labelled derivatives and compare them with [ 18 F]Galacto-RGD. For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, αvβ3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (αvβ3 positive) and M21-L (αvβ3 negative) cells were used. Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [ 68 Ga]DOTA-RGD and only up to 1.4% for [ 111 In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in αvβ3-positive tumours was 2.9 ± 0.3%ID/g and in αvβ3-negative tumours 0.8 ± 0.1%ID/g for [ 68 Ga]DOTA-RGD ([ 111 In]DOTA-RGD: 1.9 ± 0.3%ID/g and 0.5 ± 0.2%ID/g; [ 18 F]Galacto-RGD: 1.6 ± 0.2%ID/g and 0.4 ± 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [ 68 Ga]DOTA-RGD, tumour/blood ratios were higher for [ 111 In]DOTA-RGD and [ 18 F]Galacto-RGD. However, microPET studies demonstrated that visualisation of αvβ3-positive tumours using [ 68 Ga]DOTA-RGD is possible. Our data indicate that [ 68 Ga]DOTA-RGD allows monitoring of αvβ3 expression. Especially, the much easier radiosynthesis compared to [ 18 F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [ 18 F]Galacto-RGD remains superior for imaging αvβ3 expression. Introduction of alternative chelator

  15. In vivo characterization of four 68Ga-labeled multimeric RGD peptides to image αvβ3 integrin expression in two human tumor xenograft mouse models.

    Science.gov (United States)

    Lobeek, Daphne; Franssen, Gerben M; Ma, Michelle T; Wester, Hans-Jürgen; Decristoforo, Clemens; Oyen, Wim J G; Boerman, Otto C; Terry, Samantha Y A; Rijpkema, Mark

    2018-04-06

    Rationale: α v β 3 integrins play an important role in angiogenesis and cell migration of cancers. They are highly expressed on activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics of four 68 Ga-labeled multimeric cyclic arginine-glycine-aspartate RGD-based tracers in an α v β 3 integrin-expressing tumor model and in a tumor model where α v β 3 integrin is expressed solely on the neovasculature. Methods: Female BALB/c nude mice were subcutaneously injected with SK-RC-52 (α v β 3 integrin-positive) or FaDu (α v β 3 integrin-negative) tumor cells. 68 Ga-labeled DOTA-(RGD) 2 , TRAP-(RGD) 3 , FSC-(RGD) 3 , or THP-(RGD) 3 were intravenously administered to the mice (0.5 nmol per mouse, 10-20 MBq), followed by microPET/CT imaging and ex vivo biodistribution studies one hour post injection. Nonspecific uptake of the tracers in both models was determined by co-injecting an excess of unlabeled DOTA-(RGD) 2 (50 nmol) along with the radiolabeled tracers. Results: Imaging and biodistribution data showed specific uptake in the tumors for each tracer in both tumor models. Tumor uptake of [ 68 Ga]Ga-FSC-(RGD) 3 was significantly higher than that of [ 68 Ga]Ga-DOTA-(RGD) 2 , [ 68 Ga]Ga-TRAP-(RGD) 3 , and [ 68 Ga]Ga-THP-(RGD) 3 , in the SK-RC-52 model, but not in the FaDu model, where [ 68 Ga]Ga-FSC-(RGD) 3 showed significantly higher tumor uptake than [ 68 Ga]Ga-TRAP-(RGD) 3 Most importantly, differences were also observed in normal tissues and in tumor-to-blood ratios. Conclusion: All tracers showed sufficient targeting of α v β 3 integrin expression to allow for tumor detection. Although the highest tumor uptake was found for [ 68 Ga]Ga-FSC-(RGD) 3 and [ 68 Ga]Ga-THP-(RGD) 3 in the SK-RC-52 and FaDu model, respectively, selection of the most optimal tracer for specific diagnostic or therapeutic applications also depends on tumor-to-blood ratio and uptake in normal tissues, and should therefore also be considered

  16. Evaluation of two novel {sup 64}Cu-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin α{sub v}β{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Reinier; Graves, Stephen A.; Nickles, Robert J. [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); Czerwinski, Andrzej; Valenzuela, Francisco [Peptides International, Inc., Louisville, KY (United States); Chakravarty, Rubel; Yang, Yunan; England, Christopher G. [University of Wisconsin, Department of Radiology, Madison, WI (United States); Cai, Weibo [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2015-11-15

    Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin α{sub v}β{sub 3}, may offer advantages in image contrast, time for imaging, and low uptake in nontarget tissues. Two cyclic RGDfK derivatives, (PEG){sub 2}-c(RGDfK) and PEG{sub 4}-SAA{sub 4}-c(RGDfK), were constructed and conjugated to NOTA for {sup 64}Cu labeling. Their integrin α{sub v}β{sub 3}-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the {sup 64}Cu-labeled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h after injection. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers. The IC{sub 50} values of NOTA-(PEG){sub 2}-c(RGDfK) and NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) were 444 ± 41 nM and 288 ± 66 nM, respectively. Dynamic PET data of {sup 64}Cu-NOTA-(PEG){sub 2}-c(RGDfK) and {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) showed similar circulation t{sub 1/2} and peak tumor uptake of about 4 %ID/g for both tracers. Due to its marked hydrophilicity, {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintained excellent tumor-to-background ratios. Static PET scans at later time-points corroborated the enhanced excretion of the tracer, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the integrin α{sub v}β{sub 3}-specificity of the peptides. Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed fast, high-contrast PET imaging of tumor-associated integrin α{sub v}β{sub 3}. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake. (orig.)

  17. Enhancing osteogenic differentiation of MC3T3-E1 cells by immobilizing RGD onto liquid crystal substrate

    International Nuclear Information System (INIS)

    Wu, Shaopeng; Yang, Xiaohui; Li, Wenqiang; Du, Lin; Zeng, Rong; Tu, Mei

    2017-01-01

    To understand the effects of GRGDF modification on MC3T3-E1 cell behavior, we cultured these cells onto a biomimetic liquid crystalline matrix modified with GRGDF peptide (OPC-GA-RGD). Successful immobilization of GRGDF on the liquid crystalline surface was verified by fluorescent labeling, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). OPC-GA-RGDs retained its liquid crystalline feature after surface modification. The RGD-immobilized OPC substrate was hardly beneficial to initial cell adhesion but could support long-term cell survival. The enhancement in cell proliferation did not correlate with RGD density. The lower GRGDF density immobilized on the liquid crystalline OPC matrix (OPC-GA-RGD3) promoted cell adhesion, proliferation, ALP expression level and mineralization, suggesting that both the viscoelasticity-based mechanical stimuli and receptor/ligand-based biochemical cue synergistically modulate MC3T3-E1 cell behavior. - Highlight: • A novel type of GRGDF-immobilized liquid crystalline matrices was fabricated and served as a substrate for the in vitro culture of MC3T3-E1 cells. • The lower RGD density might provide a better condition for initial cell adhesion and proliferation, up-regulation of ALP expression levels, and mineralization. • The intrinsic liquid crystalline feature of OPC matrix, instead of RGD efficiency, promoted initial cell adhesion. • Properties of the liquid crystalline OPC matrix together with the stable receptor-ligand binging synergistically modulated MC3T3-E1 cell behavior.

  18. In Vitro Bioactivity Study of RGD-Coated Titanium Alloy Prothesis for Revision Total Hip Arthroplasty

    OpenAIRE

    Man, Zhentao; Sha, Dan; Sun, Shui; Li, Tao; Li, Bin; Yang, Guang; Zhang, Laibo; Wu, Changshun; Jiang, Peng; Han, Xiaojuan; Li, Wei

    2016-01-01

    Total hip arthroplasty (THA) is a common procedure for the treatment of end-stage hip joint disease, and the demand for revision THA will double by 2026. Ti6Al4V (Titanium, 6% Aluminum, and 4% Vanadium) is a kind of alloy commonly used to make hip prothesis. To promote the osseointegration between the prothesis and host bone is very important for the revision THA. The peptide Arg-Gly-Asp (RGD) could increase cell attachment and has been used in the vascular tissue engineering. In this study, ...

  19. Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

    International Nuclear Information System (INIS)

    Escudero-Castellanos, Alondra; Universidad Autonoma del Estado de Mexico, Toluca, Estado de Mexico; Ocampo-Garcia, B.E.; Ferro-Flores, Guillermina; Santos-Cuevas, C.L.; Isaac-Olive, Keila; Olmos-Ortiz, Andrea; Garcia-Quiroz, Janice; Garcia-Becerra, Rocio; Diaz, Lorenza

    2017-01-01

    This study aimed to synthesize a new 177 Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and α(v) β(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and α(v)β(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177 Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical. (author)

  20. Molecular nuclear imaging of tumoral angio genesis using a rgd-containing tracer, Raft-RGD, targeted at the neo vessel-specific integrin αvβ3

    International Nuclear Information System (INIS)

    Sancey, L.

    2006-06-01

    Tumoral neo-angio genesis targeting is currently a major field of research for the diagnostic and treatment of solid tumors. Endothelial cells from neo vessels over express several specific markers such as the α v β 3 integrin, which binds RGD (-Arg-Gly-Asp-)- containing peptides. We evaluated the potential of a novel radiotracer - RAFT-RGD - for the molecular nuclear imaging of neo vessels. In vitro, the coupling of 4 c(RGDfK) to the RAFT platform resulted in an increased cellular uptake of the tracer by α v β 3 positive cells when compared to c(RGDfK). Furthermore, RAFTRGD has a higher affinity than c(RGDfK) and similar properties for angio genesis inhibition. In vivo, both α v β 3 positive and negative tumors were visible by non invasive whole body planar and tomographic imaging from 30 min to 24 h post-injection, using a gamma camera dedicated to small animal imaging. Despite a lack of significant contrast improvement compare with c(RGDfK), RAFT-RGD could represent a promising tracer for tumoral angio genesis since it could provide invaluable information about tumor development and treatment efficacy in Nuclear Medicine departments. Furthermore, thanks to its chemical structure, RAFT-RGD can be labelled with a variety of radioisotopes including γ and β - emitters, allowing interesting therapeutical applications such as internal targeted radiotherapy. (author)

  1. DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries.

    Science.gov (United States)

    Nakamura, T; Ruiz-Lozano, P; Lindner, V; Yabe, D; Taniwaki, M; Furukawa, Y; Kobuke, K; Tashiro, K; Lu, Z; Andon, N L; Schaub, R; Matsumori, A; Sasayama, S; Chien, K R; Honjo, T

    1999-08-06

    We have identified and characterized mouse, rat, and human cDNAs that encode a novel secreted protein of 448 amino acids named DANCE (developmental arteries and neural crest epidermal growth factor (EGF)-like). DANCE contains six calcium-binding EGF-like domains, one of which includes an RGD motif. Overexpression studies of recombinant DANCE protein document that DANCE is a secreted 66-kDa protein. DANCE and recently described protein S1-5 comprise a new EGF-like protein family. The human DANCE gene was mapped at chromosome 14q32.1. DANCE mRNA is mainly expressed in heart, ovary, and colon in adult human tissues. Expression profile analysis by in situ hybridization revealed prominent DANCE expression in developing arteries. DANCE is also expressed in neural crest cell derivatives, endocardial cushion tissue, and several other mesenchymal tissues. In adult vessels, DANCE expression is largely diminished but is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells that lose their ability to proliferate in late stage of injury. DANCE protein was shown to promote adhesion of endothelial cells through interaction of integrins and the RGD motif of DANCE. DANCE is thus a novel vascular ligand for integrin receptors and may play a role in vascular development and remodeling.

  2. YY-39, a tick anti-thrombosis peptide containing RGD domain.

    Science.gov (United States)

    Tang, Jing; Fang, Yaqun; Han, Yajun; Bai, Xuewei; Yan, Xiuwen; Zhang, Yun; Lai, Ren; Zhang, Zhiye

    2015-06-01

    Ticks are obligatory blood feeding ectoparasites, which continuously attach to their hosts for 1-2 weeks. There are many biologically active compounds in tick salivary glands interfering host haemostatic system and to successfully obtain blood meal. Several platelet aggregation inhibitors have been identified from ticks. A family of conserved peptides, which were identified from transcriptome analysis of many tick salivary glands, were found to contain unique primary structure including predicted mature peptides of 39-47 amino acid residues in length and a Pro/Glu(P/E)-Pro/His(P/H)-Lys-Gly-Asp(RGD) domain. Given their unique structure and RGD domain, they are considered a novel family of disintegrins that inhibit platelet aggregation. One of them (YY-39) was tested for its effects on platelets and thrombosis in vivo. YY-39 was found effectively to inhibit platelet aggregation induced by adenosine diphosphate (ADP), thrombin and thromboxane A2 (TXA2). Furthermore, YY-39 blocked platelet adhesion to soluble collagen and bound to purified GPIIb/IIIa in a dose-dependent manner. In in vivo experiments, YY-39 reduced thrombus weight effectively in a rat arteriovenous shunt model and inhibited thrombosis in a carrageenan-induced mouse tail thrombosis model. Combined with their prevalence in ticks and platelet inhibitory functions, this family of peptides might be conserved tick anti-haemostatic molecules. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Enhanced Cellular Adhesion on Titanium by Silk Functionalized with titanium binding and RGD peptides

    Science.gov (United States)

    Vidal, Guillaume; Blanchi, Thomas; Mieszawska, Aneta J.; Calabrese, Rossella; Rossi, Claire; Vigneron, Pascale; Duval, Jean-Luc; Kaplan, David L.; Egles, Christophe

    2012-01-01

    Soft tissue adhesion on titanium represents a challenge for implantable materials. In order to improve adhesion at the cell/material interface we used a new approach based on the molecular recognition of titanium by specific peptides. Silk fibroin protein was chemically grafted with titanium binding peptide (TiBP) to increase adsorption of these chimeric proteins to the metal surface. Quartz Crystal Microbalance was used to quantify the specific adsorption of TiBP-functionalized silk and an increase in protein deposition by more than 35% was demonstrated due to the presence of the binding peptide. A silk protein grafted with TiBP and fibronectin-derived RGD peptide was then prepared. The adherence of fibroblasts on the titanium surface modified with the multifunctional silk coating demonstrated an increase in the number of adhering cells by 60%. The improved adhesion was demonstrated by Scanning Electron Microscopy and immunocytochemical staining of focal contact points. Chick embryo organotypic culture also revealed strong adhesion of endothelial cells expanding on the multifunctional silk-peptide coating. These results demonstrated that silk functionalized with TiBP and RGD represents a promising approach to modify cell-biomaterial interfaces, opening new perspectives for implantable medical devices, especially when reendothelialization is required. PMID:22975628

  4. Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Sivolapenko, G.B. [Encephalos Research and Therapeutic Inst., Athens (Greece)]|[Agii Anargiri Cancer Hospital, Athens (Greece); Skarlos, D. [Agii Anargiri Cancer Hospital, Athens (Greece); Pectasides, D. [Metaxa Cancer Hospital, Athens (Greece); Stathopoulou, E.; Milonakis, A.; Sirmalis, G.; Konstantinides, K. [Encephalos Research and Therapeutic Inst., Athens (Greece); Stuttle, A.; Courtenay-Luck, N.S.; Epenetos, A.A. [Antisoma plc., London (United Kingdom)

    1998-10-01

    Integrins are cell-surface glycoproteins found in different forms on all cells except erythrocytes. Integrins bind to cell adhesion molecules and to proteins found in the extracellular matrix. A tripeptidic sequence Arg-Gly-Asp (RGD) is often the primary site of recognition by integrins which are expressed on tumour cells and are responsible for tumour invasion and metastasis. A synthetic decapeptide designated {alpha}P2 containing two RGD sequences radiolabelled with technetium-99m was used to image malignant melanoma in vivo. Fourteen patients previously diagnosed with metastatic melanoma underwent gamma camera imaging 20-180 min following intravenous administration of the radiolabelled synthetic decapeptide {alpha}P2. Six out of eight (6/8) of the lymph node metastases (75%) and all other neoplastic sites (11 sites) were successfully imaged, with the exception of three sites in the mediastinal area which were not positively imaged. In two cases there was false positive uptake in the rounded pigmented areolar/nipple area. In three cases (seven sites) the peptide scan confirmed the absence of disease in suspected lesions (true-negative). The synthetic peptide was rapidly removed from the circulation by filtration through the kidneys and excretion in the urine. No toxicity or adverse events were recorded. Radiolabelled {alpha}P2 peptide, which binds specifically to adhesion molecules on tumours, can be used for the in vivo detection of neoplastic metastases. (orig.) With 5 figs., 2 tabs., 24 refs.

  5. Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene (TPX with cRGD pentapeptide

    Directory of Open Access Journals (Sweden)

    Lena Möller

    2013-02-01

    Full Text Available Covalent multistep coating of poly(methylpentene, the membrane material in lung ventilators, by using a copper-free “click” approach with a modified cyclic RGD peptide, leads to a highly biocompatible poly(methylpentene surface. The resulting modified membrane preserves the required excellent gas-flow properties while being densely seeded with lung endothelial cells.

  6. PET imaging of alphavbeta integrin expression in tumours with Ga-labelled mono-, di- and tetrameric RGD peptides

    NARCIS (Netherlands)

    Dijkgraaf, I.; Yim, C.B.; Franssen, G.M.; Schuit, R.C.; Luurtsema, G.; Liu, S.; Oyen, W.J.G.; Boerman, O.C.

    2011-01-01

    PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared

  7. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Liu, S.; Kruijtzer, J.A.; Soede, A.C.; Oyen, W.J.G.; Liskamp, R.M.; Corstens, F.H.M.; Boerman, O.C.

    2007-01-01

    INTRODUCTION: Due to the selective expression of the alpha(v)beta3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study,

  8. Development of a strategy to functionalize a dextrin-based hydrogel for animal cell cultures using a starch-binding module fused to RGD sequence

    Directory of Open Access Journals (Sweden)

    Gama Miguel

    2008-10-01

    Full Text Available Abstract Background Several approaches can be used to functionalize biomaterials, such as hydrogels, for biomedical applications. One of the molecules often used to improve cells adhesion is the peptide Arg-Gly-Asp (RGD. The RGD sequence, present in several proteins from the extra-cellular matrix (ECM, is a ligand for integrin-mediated cell adhesion; this sequence was recognized as a major functional group responsible for cellular adhesion. In this work a bi-functional recombinant protein, containing a starch binding module (SBM and RGD sequence was used to functionalize a dextrin-based hydrogel. The SBM, which belongs to an α-amylase from Bacillus sp. TS-23, has starch (and dextrin, depolymerized starch affinity, acting as a binding molecule to adsorb the RGD sequence to the hydrogel surface. Results The recombinant proteins SBM and RGD-SBM were cloned, expressed, purified and tested in in vitro assays. The evaluation of cell attachment, spreading and proliferation on the dextrin-based hydrogel surface activated with recombinant proteins were performed using mouse embryo fibroblasts 3T3. A polystyrene cell culture plate was used as control. The results showed that the RGD-SBM recombinant protein improved, by more than 30%, the adhesion of fibroblasts to dextrin-based hydrogel. In fact, cell spreading on the hydrogel surface was observed only in the presence of the RGD-SBM. Conclusion The fusion protein RGD-SBM provides an efficient way to functionalize the dextrin-based hydrogel. Many proteins in nature that hold a RGD sequence are not cell adhesive, probably due to the conformation/accessibility of the peptide. We therefore emphasise the successful expression of a bi-functional protein with potential for different applications.

  9. Evaluation of the therapeutic efficacy and radiotoxicity of the conjugates {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} and {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfk(C)] in a murine model and their relationship with the inhibition of the angiogenic factors VEGF and HIF-1α; Evaluacion de la eficacia terapeutica y radiotoxicidad de los conjugados {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} y {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfK(C)] en un modelo murino y su relacion con la inhibicion de los factores angiogenicos VEGF y HIF-1α

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2013-07-01

    Molecular targeting therapy has become a relevant therapeutic strategy for cancer. The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been proven, and radiolabeled peptides have been demonstrated to be effective in patients with malignant tumors. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of α(v)β(3) integrin, thereby inhibiting angio genesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable m ultimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of {sup 177}Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare with that of {sup 177}Lu-AuNP or {sup 177}Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-micro PET/CT), renal radiotoxicity, renal and tumoral histological characteristics as well as tumoral VEGF and HIF-1? gene expression (by realtime polymerase chain reaction) following treatment with {sup 177}Lu-AuNP-RGD, {sup 177}Lu-AuNP or {sup 177}Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, {sup 177}Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 ± 7.9 Gy) vs other treatments. These results correlated with the observed therapeutic response, in which {sup 177}Lu-AuNP-RGD significantly (p<0.05) reduced tumor progression, tumor metabolic activity, intratumoral vessels and VEGF gene expression compared to the other radiopharmaceuticals. This was consequence of high tumor retention and a combination of molecular targeting therapy (m ultimeric RGD system) and radiotherapy ({sup 177}Lu). There was a low uptake in non-target organs and no induction of renal toxicity. {sup 177}Lu-AuNP-RGD demonstrates properties suitable for use as an agent for molecular targeting radiotherapy. (Author)

  10. cRGD-directed, NIR-responsive and robust AuNR/PEG-PCL hybrid nanoparticles for targeted chemotherapy of glioblastoma in vivo.

    Science.gov (United States)

    Zhong, Yinan; Wang, Chao; Cheng, Ru; Cheng, Liang; Meng, Fenghua; Liu, Zhuang; Zhong, Zhiyuan

    2014-12-10

    cRGD-directed, NIR-responsive and robust AuNR/PEG-PCL hybrid nanoparticles (cRGD-HNs) were designed and developed for targeted chemotherapy of human glioma xenografts in mice. As expected, cRGD-HNs had excellent colloidal stability. The in vitro release studies showed that drug release from DOX-loaded cRGD-HNs (cRGD-HN-DOX) was minimal under physiological conditions but markedly accelerated upon NIR irradiation at a low power density of 0.2 W/cm2, due to photothermally induced phase transition of PCL regime. MTT assays showed that the antitumor activity of cRGD-HN-DOX in αvβ3 integrin over-expressed human glioblastoma U87MG cells was greatly boosted by mild NIR irradiation, which was significantly more potent than non-targeting HN-DOX counterpart under otherwise the same conditions and was comparable or superior to free DOX, supporting receptor-mediated endocytosis mechanism. The in vivo pharmacokinetics studies showed that cRGD-HN-DOX had much longer circulation time than free DOX. The in vivo imaging and biodistribution studies revealed that cRGD-HN-DOX could actively target human U87MG glioma xenograft in nude mice. The therapeutic studies in human U87MG glioma xenografts exhibited that cRGD-HN-DOX in combination with NIR irradiation completely inhibited tumor growth and possessed much lower side effects than free DOX. The Kaplan-Meier survival curves showed that all mice treated with cRGD-HN-DOX plus NIR irradiation survived over an experimental period of 48 days while control groups treated with PBS, cRGD-HN-DOX, cRGD-HNs with NIR irradiation, free DOX, or HN-DOX with NIR irradiation (non-targeting control) had short life spans of 15-40 days. Ligand-directed AuNR/PEG-PCL hybrid nanoparticles with evident tumor-targetability as well as superior spatiotemporal and rate control over drug release have emerged as an appealing platform for cancer chemotherapy in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Targeted radionuclide therapy with RAFT-RGD radiolabelled with {sup 90}Y or {sup 177}Lu in a mouse model of αvβ3-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bozon-Petitprin, A.; Bacot, S.; Ahmadi, M.; Marti-Batlle, D.; Perret, P.; Broisat, A.; Riou, L.M. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); Gauchez, A.S.; Bourre, J.C.; Fagret, D.; Vuillez, J.P. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); CHRU Grenoble, Hopital Michallon, Service de Medecine Nucleaire, Grenoble (France); Claron, M.; Boturyn, D. [CNRS, UMR 5250, Departement de Chimie Moleculaire, Grenoble (France); Ghezzi, Catherine [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); INSERM U1039, Radiopharmaceutiques biocliniques, Batiment Jean Roget, Domaine de la Merci, Faculte de Medecine, La Tronche (France)

    2014-08-28

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK]){sub 4} (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β{sup -} emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD and {sup 90}Y-RAFT-RAD or {sup 177}Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of {sup 90}Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of {sup 177}Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of {sup 90}Y-RAFT-RAD or 37 MBq of {sup 177}Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of {sup 90}Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. {sup 90}Y-RAFT-RGD and {sup 177}Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy. (orig.)

  12. Qualidade conjugal: mapeando conceitos

    Directory of Open Access Journals (Sweden)

    Clarisse Mosmann

    2006-12-01

    Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

  13. Conjugated Polymer Solar Cells

    National Research Council Canada - National Science Library

    Paraschuk, Dmitry Y

    2006-01-01

    This report results from a contract tasking Moscow State University as follows: Conjugated polymers are promising materials for many photonics applications, in particular, for photovoltaic and solar cell devices...

  14. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  15. Endothelial cell adhesion and proliferation to PEGylated polymers with covalently linked RGD peptides.

    Science.gov (United States)

    Wang, Xin; Heath, Daniel E; Cooper, Stuart L

    2012-03-01

    A nonfouling peptide grafted polymer was synthesized that can promote endothelial cell (EC) binding. The polymer was composed of hexyl methacrylate, methyl methacrylate, poly(ethylene glycol) methacrylate, and CGRGDS peptide. The peptide was incorporated into the polymer system either by a chain transfer reaction or by coupling to an acrylate-PEG-N-hydroxysuccinimide (NHS) comonomer. The introduction of PEG chains minimizes protein adsorption. Human umbilical vein ECs and endothelial colony forming cells were cultured on these surfaces in short term and long-term studies. A difference in number and morphology of ECs was observed depending on the method of peptide incorporation. Both cell types adhered better to polymer films containing NHS coupled RGD peptide after 2 h even in the presence of albumin but significant cell detachment occurred after 4 days. Polymer solutions were electrospun into fibrous scaffolds. Both nonfouling and peptide binding characteristics were retained after processing. Copyright © 2012 Wiley Periodicals, Inc.

  16. Construction of expressing vectors including melanoma differentiation-associated gene-7 (mda-7 fused with the RGD sequences for better tumor targeting

    Directory of Open Access Journals (Sweden)

    Mahboobeh Khodadad

    2015-08-01

    Conclusion: Theoretically RGD tagged mda-7 would be able to induce apoptosis with more specificity and stronger than the standard one, therefore, these new constructs may have the potential for further researches.

  17. A rapid and clean synthetic approach to cyclic peptides via micro-flow peptide chain elongation and photochemical cyclization: synthesis of a cyclic RGD peptide.

    Science.gov (United States)

    Mifune, Yuto; Nakamura, Hiroyuki; Fuse, Shinichiro

    2016-11-29

    A cyclic RGD peptide was efficiently synthesized based on micro-flow, triphosgene-mediated peptide chain elongation and micro-flow photochemical macrolactamization. Our approach enabled a rapid (amidation for peptide chain elongation peptide.

  18. Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

    Science.gov (United States)

    Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

    2017-04-13

    In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD

  19. A pilot study imaging integrin αvβ3 with RGD PET/CT in suspected lung cancer patients.

    Science.gov (United States)

    Gao, Song; Wu, Honghu; Li, Wenwu; Zhao, Shuqiang; Teng, Xuepeng; Lu, Hong; Hu, Xudong; Wang, Suzhen; Yu, Jinming; Yuan, Shuanghu

    2015-12-01

    Angiogenesis is an essential step in tumour development and metastasis. Integrin αvβ3 plays a major role in angiogenesis, tumour growth and progression. A new tracer, (18)F-AL-NOTA-PRGD2, denoted as (18)F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin αvβ3. This is a pilot study to test the safety and diagnostic value of (18)F- arginine-glycine-aspartic acid (RGD) PET/computed tomography (CT) in suspected lung cancer patients. Twenty-six patients with suspected lung cancer on enhanced CT underwent (18)F-alfatide RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUVs) and the tumour-to-blood ratios were measured, and diagnoses were pathologically confirmed. RGD PET/CT with (18)F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed. The (18)F-alfatide RGD PET/CT analysis correctly recognized 17 patients with lung cancer, 4 patients (hamartoma) as true negative, and 5 patients (4 chronic inflammation and 1 inflammatory pseudotumour) as false positive. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of (18)F-alfatide RGD PET/CT for the diagnosis of suspected lung cancer patients was 100, 44.44, 80.77, 77.27, and 100%, respectively. The area under a receiver operating characteristic (ROC) curve was 0.75 (P = 0.038), and ROC analysis suggested an SUVmax cut-off value of 2.65 to differentiate between malignant lesions and benign lesions. The SUV for malignant lesions was 5.37 ± 2.17, significantly higher than that for hamartomas (1.60 ± 0.11; P  0.05). Sixteen of 26 patients later underwent successful surgery, and pathologic examination confirmed nodes positive for metastasis in 14 of 152 lymph nodes. The sensitivity, specificity, accuracy, PPV, and NPV of PET/CT for lymph nodes was 92.86, 95.65, 95.40, 61.90, and 99.25%, respectively. Our results suggest that

  20. [{sup 68}Ga]NODAGA-RGD - Metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Haubner, Roland; Rangger, Christine; Decristoforo, Clemens; Virgolini, Irene J. [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Finkenstedt, Armin; Zoller, Heinz [Medical University of Innsbruck, Department of Internal Medicine II, Innsbruck (Austria); Stegmayr, Armin [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); FH Gesundheit/University of Applied Sciences Tyrol, Innsbruck (Austria)

    2016-10-15

    This study was designed to determine safety, tolerability, and radiation burden of a [{sup 68}Ga]NODAGA-RGD-PET for imaging integrin α{sub v}β{sub 3} expression in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Moreover, metabolic stability and biokinetic data were compiled. After injection of 154-184 MBq [{sup 68}Ga]NODAGA-RGD three consecutive PET/CT scans were acquired starting 8.3 ± 2.1, 36.9 ± 2.8, and 75.1 ± 3.4 min after tracer injection. For metabolite analysis, blood and urine samples were analyzed by HPLC. For dosimetry studies, residence time VOIs were placed in the corresponding organs. The OLINDA/EXM program was used to estimate the absorbed radiation dose. The radiopharmaceutical was well tolerated and no drug-related adverse effects were observed. No metabolites could be detected in blood (30 and 60 min p.i.) and urine (60 min p.i.). [{sup 68}Ga]NODAGA-RGD showed rapid and predominantly renal elimination. Background radioactivity in blood, intestine, lung, and muscle tissue was low (%ID/l 60 min p.i. was 0.56 ± 0.43, 0.54 ± 0.39, 0.22 ± 0.05, and 0.16 ± 0.8, respectively). The calculated effective dose was 21.5 ± 5.4 μSv/MBq, and the highest absorbed radiation dose was found for the urinary bladder wall (0.26 ± 0.09 mSv/MBq). No increased uptake of the tracer was found in HCC compared with the background liver tissue. [{sup 68}Ga]NODAGA-RGD uptake in the HCCs lesions was not sufficient to use this tracer for imaging these tumors. [{sup 68}Ga]NODAGA-RGD was well tolerated and metabolically stable. Due to rapid renal excretion, background radioactivity was low in most of the body, resulting in low radiation burden and indicating the potential of [{sup 68}Ga]NODAGA-RGD PET for non-invasive determination of integrin α{sub v}β{sub 3} expression. (orig.)

  1. Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects.

    Science.gov (United States)

    Song, Zhiwang; Lin, Yun; Zhang, Xia; Feng, Chan; Lu, Yonglin; Gao, Yong; Dong, Chunyan

    2017-01-01

    Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin α v β 3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer.

  2. Optimization of a siRNA Carrier Modified with a pH-Sensitive Cationic Lipid and a Cyclic RGD Peptide for Efficiently Targeting Tumor Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Tomoya Hada

    2015-09-01

    Full Text Available In recent years, anti-angiogenic therapy has attracted much interest because it is a versatile approach to treating most types of tumors, and therefore would be expected to be applicable for various cancers. Severe adverse events in patients treated with currently available anti-angiogenic therapeutics have, however, been reported, and these are caused by their inhibitory effects in normal tissue. To achieve an efficient anti-angiogenic therapy with minimal toxicity, a drug delivery system (DDS specific to tumor endothelial cells (TECs is needed. Cyclic RGD (cRGD is a well-known ligand against αVβ3 integrin that is expressed at high levels in the cell surface of TECs. To address this issue, we previously developed a cyclic RGD-equipped liposomal DDS (RGD-MEND in which small interfering RNA (siRNA was encapsulated. However, in the previous study, details of the preparation steps were not thoroughly examined. In this paper, to produce the most efficient delivery of therapeutic TECs, we explored optimum preparation conditions and components of the RGD-MEND. The cellular uptake and silencing ability of the RGD-MEND were investigated as a function of ligand density, poly(ethyleneglycol linker length, and lipid composition. As a result, a knockdown efficiency that was five-fold higher than that of the previously reported one (ED50, from 4.0 to 0.75 mg/kg was achieved.

  3. Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus

    Directory of Open Access Journals (Sweden)

    Ahmed Abdullah Al-Zaher

    2018-03-01

    Full Text Available To enhance adenovirus-mediated oncolysis, different approaches that tackle the selectivity, tumor penetration, and spreading potential of oncolytic adenoviruses have been reported. We have previously demonstrated that insertion of the internalizing Arginine-Glycine-Aspartic (iRGD tumor-penetrating peptide at the C terminus of the fiber or transgenic expression of a secreted hyaluronidase can improve virus tumor targeting and spreading. Here we report a new oncolytic adenovirus ICOVIR17K-iRGD in which both modifications have been incorporated. In xenografted A549 tumors in nude mice, ICOVIR17K-iRGD shows higher efficacy than the non-iRGD counterpart. To gain insights into the role of the immune system in oncolysis, we have studied ICOVIR17K-iRGD in the tumor isograft mouse model CMT64.6, partially permissive to human adenovirus 5 replication, in immunodeficient or immunocompetent mice. Whereas no efficacy was observed in the immunodeficient setting due to insufficient viral replication, partial efficacy and a polymorphonuclear and CD8+ T cell infiltrate were observed in the immunocompetent mice. The results indicate that the elicitation of a virus-induced anti-tumoral immune response is responsible for the observed partial anti-tumoral effect. Keywords: oncolytic adenovirus, iRGD tumor-penetrating peptide, immune response

  4. Optimization of the production process of hybrid and multivalent formulation Bombesin/RGD for the opportune detection of breast cancer

    International Nuclear Information System (INIS)

    Robles M, M.

    2013-01-01

    The radiopharmaceuticals of third generation are used in nuclear medicine to obtain images of specific molecular targets, and they are unique in their capacity to detect in vivo specific biochemical sites as receptors that are over-expressed in diverse illness. In cancer cells several types of receptors are over-expressed, as the integrin s α(v)β(3) and α(v)β(5) that specifically recognize the sequence RGD (Arginine-Glycin-Ac. Aspartic) and gastrin-releasing peptide that recognizes specifically to the peptide Lys 3 -Bombesin. The integrin s α(v)β(3) and α(v)β(5) are involved in the tumor angio genesis processes and the gastrin-releasing peptide is over-expressed in breast and prostate cancer. The molecular recognition of the specific receptors is the basis to be utilized as targets of the radiopharmaceuticals 99m Tc-HYNIC-Bombesin and 99m Tc-HYNIC-RGD. In this work was developed a lyophilized pharmaceutical formulation effective, stable and safe for the simultaneous obtaining of the radiopharmaceuticals 99m Tc-HYNIC-Bombesin ( 99m Tc-EDDA/HYNIC-Lys 3 -Bombesin) and 99m Tc-HYNIC-RGD ( 99m Tc EDDA/HYNIC-E-[c(RGDfK)] 2 ). Later on the production process of the product HYNIC-Bombesin/RGD-Sn was optimized using a factorial design and the formulation was transferred to the production plant of radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ). The optimized formulation is described in the following chart: HYNIC-[Lys 3 ]-Bombesin - 12.5 μg; HYNIC-E-c[RGDfK] 2 - 12.5 μg; Stannous chloride (SnCl 2 ) - 20 μg; Ethylenediamine diacetic acid (EDDA) - 10 mg; N-tris(hydroxymethyl)methyl glycin (Tricine) - 20 mg; Mannitol - 50 mg. The production process was validated and were carried out the stability studies under refrigeration conditions. (Author)

  5. Use of RGD-Functionalized Sandwich Cultures to Promote Redifferentiation of Human Pancreatic Beta Cells After In Vitro Expansion.

    Science.gov (United States)

    Aloy-Reverté, Caterina; Moreno-Amador, José L; Nacher, Montserrat; Montanya, Eduard; Semino, Carlos E

    2018-03-01

    Islet transplantation has provided proof of concept that cell therapy can restore normoglycemia in patients with diabetes. However, limited availability of islet tissue severely restricts the clinical use of the treatment. Thus, there is an urgent need to develop new strategies to generate an abundant source of insulin-producing cells that could be used to treat diabetes. A potential approach is the in vitro expansion of pancreatic beta cells obtained from cadaveric organ donors. However, when human beta cells are expanded in vitro, they dedifferentiate and lose the expression of insulin, probably as a consequence of pancreatic islet dissociation into single cells. We have studied whether reestablishment of cell-cell and cell-matrix relationships with a biomimetic synthetic scaffold could induce redifferentiation of expanded dedifferentiated beta cells. Cells isolated from human islet preparations were expanded in monolayer cultures and allowed to reaggregate into islet-like cell clusters (ICCs). Afterward, ICCs were embedded between two thin layers of the noninstructive self-assembling peptide (SAP), RAD16-I or RAD16-I functionalized with the integrin-binding motif RGD (RAD16-I/RGD) (R: arginine, G: glycine, D: aspartic acid), which was expected to promote cell-extracellular matrix interactions. ICCs cultured with RAD16-I were viable, maintained their cluster conformation, and increased in size by aggregation of ICCs, suggesting a self-organizing process. ICCs cultured in RAD16-I/RGD showed enhanced cell adhesion to RAD16-I matrix and reexpression of the beta cell-specific genes, Ins, Pdx1, Nkx6.1, and MafA. Redifferentiation was caused solely by bioactive cues introduced to the RAD16-I peptide since no differentiation factors were added to the culture medium. The results indicate that RGD-functionalized SAP in sandwich conformation is a promising three-dimensional platform to induce redifferentiation toward a beta cell phenotype and to generate insulin

  6. Induction of Chondrogenic Differentiation of Human Mesenchymal Stem Cells by Biomimetic Gold Nanoparticles with Tunable RGD Density.

    Science.gov (United States)

    Li, Jingchao; Li, Xiaomeng; Zhang, Jing; Kawazoe, Naoki; Chen, Guoping

    2017-07-01

    Nanostructured materials have drawn a broad attention for their applications in biomedical fields. Ligand-modified nanomaterials can well mimic the dynamic extracellular matrix (ECM) microenvironments to regulate cell functions and fates. Herein, ECM mimetic gold nanoparticles (Au NPs) with tunable surface arginine-glycine-aspartate (RGD) density are designed and synthesized to induce the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The biomimetic Au NPs with an average size of 40 nm shows good biocompatibility without affecting the cell proliferation in the studied concentration range. The RGD motifs on Au NPs surface facilitate cellular uptake of NPs into monolayer hMSCs through integrin-mediated endocytosis. The biomimetic NPs have a promotive effect on cartilaginous matrix production and marker gene expression in cell pellet culture, especially for the biomimetic Au NPs with high surface RGD density. This study provides a novel strategy for fabricating biomimetic NPs to regulate cell differentiation, which holds great potentials in tissue engineering and biomedical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. RGD-functionalized polyethylene glycol hydrogels support proliferation and in vitro chondrogenesis of human periosteum-derived cells.

    Science.gov (United States)

    Kudva, Abhijith K; Luyten, Frank P; Patterson, Jennifer

    2018-01-01

    The combination of progenitor cells with appropriate scaffolds and in vitro culture regimes is a promising area of research in bone and cartilage tissue engineering. Mesenchymal stem cells (MSCs), when encapsulated within hydrogels composed of the necessary cues and/or preconditioned using suitable culture conditions, have been shown to differentiate into bone or cartilage. Here, we utilized human periosteum-derived cells (hPDCs), a progenitor cell population with MSC characteristics, paired with protease-degradable, functionalized polyethylene glycol (PEG) hydrogels to create tissue-engineered constructs. The objective of this study was to investigate the effects of scaffold composition, exploring the addition of the cell-binding motif Arginine-Glycine-Aspartic Acid (RGD), in combination with various in vitro culture conditions on the proliferation, chondrogenic gene expression, and matrix production of encapsulated hPDCs. In growth medium, the hPDCs in the RGD-functionalized hydrogels maintained high levels of viability and demonstrated an enhanced proliferation when compared with hPDCs in non-functionalized hydrogels. Additionally, the RGD-containing hydrogels promoted higher glycosaminoglycan (GAG) synthesis and chondrogenic gene expression of the encapsulated hPDCs, as opposed to the non-functionalized constructs, when cultured in two different chondrogenic media. These results demonstrate the potential of hPDCs in combination with enzymatically degradable PEG hydrogels functionalized with adhesion ligands for cartilage regenerative applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 33-42, 2018. © 2017 Wiley Periodicals, Inc.

  8. Inducing Optimal Antitumor Immune Response through Coadministering iRGD with Pirarubicin Loaded Nanostructured Lipid Carriers for Breast Cancer Therapy.

    Science.gov (United States)

    Deng, Caifeng; Jia, Mengdi; Wei, Guangfei; Tan, Tiantian; Fu, Yao; Gao, Huile; Sun, Xun; Zhang, Quan; Gong, Tao; Zhang, Zhirong

    2017-01-03

    Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death. Subsequently, the cytotoxic T lymphocytes (CD3 + and CD8 + cells) infiltration and cytokine (IFN-γ and INF-α) secretion in tumors were heavily increased. The efficient T-cell dependent control of tumors in the late stage and the lower side effects contributed to the longest whole survival of THP-NLC + iRGD treated mice. Therefore, the coadministration of THP-NLC with iRGD resulted in increased tumor cell direct-killing death and enhanced antitumor immune response. Our results illustrated that THP could serve as an immunogenic cell death inducer and the proposed drug delivery strategy might impact cancer immunotherapy by arousing increased immunogenic tumor cell death.

  9. Synthesis and characterization of a new class of glycosylated porphyrins bearing the RGD moiety and their application in photodynamic therapy

    International Nuclear Information System (INIS)

    Chaleix, Vincent

    2003-01-01

    The use of porphyrins and analogues as photosensitisers together with visible light is a new treatment of tumors (photodynamic therapy, PDT). Carbohydrate-substituted porphyrins are in this domain very promising compounds. In addition, it is known that endothelial cells of the neo-vascularisation in tumors express αVβ3 integrin. Extracellular domains of this transmembrane glycoprotein are able to bind components of the extracellular matrix (ECM) and more precisely the sequence Arg-Gly-Asp. With the aim of their utilization in photodynamic therapy of cancers, we describe the synthesis and characterization (UV-Visible, mass, NMR) of new glucosylated porphyrins bearing the RGD moiety. The first synthesised compounds were derived from tritolyl and tri-glucosyl-aryl-porphyrins where the peptidic moiety is linked to the phenyl group by a spacer arm by means of a solid phase reaction.. The second series consists of glucosylated porphyrin derivatives bearing a cyclical unsaturated pentapeptide including RGD sequence, obtained by ring closing metathesis in solid phase. We have also synthesized a dimer in which the two glucosylated porphyrins are linked by the RGD sequence. These compounds produced 1 O 2 and photo-cyto-toxicities against K562 leukemia cell line were favourably compared to Photofrin II R . Due to their sensitising abilities, these compounds are of considerable interest for photodynamic therapy. (author) [fr

  10. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  11. Photoluminescence in conjugated polymers

    International Nuclear Information System (INIS)

    Furst, J.E.; Laugesen, R.; Dastoor, P.; McNeill, C.

    2002-01-01

    Full text: Conjugated polymers combine the electronic and optical properties of semiconductors with the processability of polymers. They contain a sequence of alternate single and double carbon bonds so that the overlap of unhybridised p z orbitals creates a delocalised ρ system which gives semiconducting properties with p-bonding (valence) and p* -antibonding (conduction) bands. Photoluminesence (PL) in conjugated polymers results from the radiative decay of singlet excitons confined to a single chain. The present work is the first in a series of studies in our laboratory that will characterize the optical properties of conjugated polymers. The experiment involves the illumination of thin films of conjugated polymer with UV light (I=360 nm) and observing the subsequent fluorescence using a custom-built, fluorescence spectrometer. Photoluminesence spectra provide basic information about the structure of the polymer film. A typical spectrum is shown in the accompanying figure. The position of the first peak is related to the polymer chain length and resolved multiple vibronic peaks are an indication of film structure and morphology. We will also present results related to the optical degradation of these materials when exposed to air and UV light

  12. Ultraviolet phase conjugation

    International Nuclear Information System (INIS)

    Slatkine, M.; Bigio, I.J.; Fisher, R.A.; Maloney, M.L.; Busse, J.R.; Tercovich, R.G.; Feldman, B.J.

    1981-01-01

    Diffraction-limited phase conjugate reflection of an injection-locked high-power (approx. 1 MW) ultraviolet excimer laser beam has been demonstrated via stimulated Brillouin scattering. Reflectivities higher than 70% were attained. Limitations as well as coherence and power requirements for image retention are discussed

  13. Crisis and Conjugal Power

    Science.gov (United States)

    Bahr, Stephen L.; Rollins, Boyd C.

    1971-01-01

    It was hypothesized that the more equalitarian the conjugal power structure in a noncrisis situation, the more likely the relative marital power will change during a crisis. This was tested using an observational experimental method, and the hypothesis was supported. (Author/CG)

  14. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  15. Poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds coated with PhaP-RGD fusion protein promotes the proliferation and chondrogenic differentiation of human umbilical cord mesenchymal stem cells in vitro.

    Science.gov (United States)

    Li, Xiaoli; Chang, Huimin; Luo, Huanan; Wang, Zhenghui; Zheng, Guoxi; Lu, Xiaoyun; He, Xijing; Chen, Fang; Wang, Ting; Liang, Jianmin; Xu, Min

    2015-03-01

    Human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs) have been widely used in tissue engineering. The aim of this study is to evaluate the ability of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) scaffolds coated with polyhydroxyalkanoate binding protein fused with arginyl-glycyl-aspartic acid (PhaP-RGD) to promote the proliferation and chondrogenic differentiation of hUC-MSCs seeded on them. The PhaP-RGD fusion protein was expressed by Escherichia coli. PHBHHx films were coated with PhaP-RGD fusion protein and the physiochemical properties were examined. hUC-MSCs were seeded on PHBHHx films with or without PhaP-RGD precoating and tested for changes in morphology, viability, and chondrogenic differentiation. We found that PhaP-RGD-coated PHBHHx films had similar surface morphology to uncoated PHBHHx. The water contact angle of the coated PHBHHx surface was lower than that of the uncoated surface (10.63° vs. 98.69°). At 7 and 14 days after seeding, the PhaP-RGD-coated PHBHHx group showed greater numbers of viable cells compared to the uncoated PHBHHx group. The expression levels of aggrecan and collagen II were enhanced in the PhaP-RGD-coated PHBHHx group relative to the uncoated PHBHHx group. Histological analysis using toluidine blue staining showed elevated formation of proteoglycan producing chondrocytes in the PhaP-RGD-coated PHBHHx group. Additionally, the synthesis of proteoglycan and collagen was significantly enhanced within the PhaP-RGD constructs. Taken together, PhaP-RGD coating promotes the proliferation and chondrogenic differentiation of hUC-MSCs seeded on PHBHHx films. PhaP-RGD-coated PHBHHx may be a useful scaffold for cartilage tissue engineering. © 2014 Wiley Periodicals, Inc.

  16. Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold.

    Science.gov (United States)

    Moshaverinia, Alireza; Chen, Chider; Xu, Xingtian; Akiyama, Kentaro; Ansari, Sahar; Zadeh, Homayoun H; Shi, Songtao

    2014-02-01

    Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD- (arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

  17. Three-Dimensional Graphene–RGD Peptide Nanoisland Composites That Enhance the Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Ee-Seul Kang

    2018-02-01

    Full Text Available Graphene derivatives have immense potential in stem cell research. Here, we report a three-dimensional graphene/arginine-glycine-aspartic acid (RGD peptide nanoisland composite effective in guiding the osteogenesis of human adipose-derived mesenchymal stem cells (ADSCs. Amine-modified silica nanoparticles (SiNPs were uniformly coated onto an indium tin oxide electrode (ITO, followed by graphene oxide (GO encapsulation and electrochemical deposition of gold nanoparticles. A RGD–MAP–C peptide, with a triple-branched repeating RGD sequence and a terminal cysteine, was self-assembled onto the gold nanoparticles, generating the final three-dimensional graphene–RGD peptide nanoisland composite. We generated substrates with various gold nanoparticle–RGD peptide cluster densities, and found that the platform with the maximal number of clusters was most suitable for ADSC adhesion and spreading. Remarkably, the same platform was also highly efficient at guiding ADSC osteogenesis compared with other substrates, based on gene expression (alkaline phosphatase (ALP, runt-related transcription factor 2, enzyme activity (ALP, and calcium deposition. ADSCs induced to differentiate into osteoblasts showed higher calcium accumulations after 14–21 days than when grown on typical GO-SiNP complexes, suggesting that the platform can accelerate ADSC osteoblastic differentiation. The results demonstrate that a three-dimensional graphene–RGD peptide nanoisland composite can efficiently derive osteoblasts from mesenchymal stem cells.

  18. Dual targeting strategy of magnetic nanoparticle-loaded and RGD peptide-activated stimuli-sensitive polymeric micelles for delivery of paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Meng Meng [Tsinghua University, Department of Chemical Engineering (China); Kang, Yoon Joong [Jungwon University, Department of Biomedical Science (Korea, Republic of); Sohn, Youngjoo [Kyung Hee University, Department of Anatomy, College of Korean Medicine (Korea, Republic of); Kim, Do Kyung, E-mail: eurokorean@gmail.com, E-mail: dokyung@konyang.ac.kr [Konyang University, Industry Cooperation Foundation (Korea, Republic of)

    2015-06-15

    A double targeting strategy of anti-neoplastic agent paclitaxel (PTX) was developed by incorporating magnetic nanoparticles and RGD peptide for enhanced cell cytotoxicity effect at lower dosage. A dual targeting mechanism including magnetic targeting and RGD ligand-specific targeting enhanced the overall cytotoxicity and reduced the effective dosage of PTX to achieve enhanced and sustained release of PTX in vitro. We addressed the issues of water-insolubility of oleic acid (OA)-stabilized SPIONs and low incorporation efficiency of hydrophobic PTX with SPION nanocarriers by using an amphiphilic polymer poly[(N-isopropylacrylamide-r-acrylamide)-b-l-lactic acid] (PNAL) as micelle-forming materials. A targeting moiety, GGGGRGD peptide, a RGD sequence-containing peptide with a short linker, is attached to the surface of PNAL-SPIONs via a homo-crosslinker. Confocal microscopy image analysis revealed that the cellular uptake was increased from (1.5 ± 0.5 % (PNAL) to 11.7 ± 0.8 % (RGD-PNAL-SPIONs) at 6 h incubation, once both RGD peptide and magnetic force attraction were incorporated into the carriers. Such multi-targeting nanocarriers showed promising potential in cancer-oriented diagnosis and therapy.

  19. High Mobility Conjugated Polymers

    Science.gov (United States)

    2007-10-20

    blends with poly(3- hexylthiophene) (PHT) could be readily fabricated as uniform nanofibers by co- electrospinning their solutions with another solution...We have demonstrated that nanofibers of conjugated 10 - polymers and their blends could be conveniently fabricated by electrospinning . Furthermore, we...luminance o - - characteristics of an ITO/ PEDOT /TAPC k D r a Vol gt, V, (V) /BPQ-PPO/LiF/A! device are shown in Fig. 30. (A) Current density-voltage

  20. A pilot study imaging integrin αvβ3 with RGD PET/CT in suspected lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Song [Shandong Cancer Hospital and Institute, Department of Radiation Oncology, Jinan, Shandong (China); University of Jinan-Shandong Academy of Medical Sciences, School of Medicine and Life Sciences, Jinan, Shandong (China); Wu, Honghu [Wuyi County People' s Hospital of Hengshui City, Hengshui, Hebei Province (China); Li, Wenwu; Zhao, Shuqiang; Teng, Xuepeng; Lu, Hong [Shandong Cancer Hospital and Institute, Department of Radiology, Jinan, Shandong (China); Hu, Xudong; Wang, Suzhen; Yu, Jinming; Yuan, Shuanghu [Shandong Cancer Hospital and Institute, Department of Radiation Oncology, Jinan, Shandong (China)

    2015-12-15

    Angiogenesis is an essential step in tumour development and metastasis. Integrin αvβ3 plays a major role in angiogenesis, tumour growth and progression. A new tracer, {sup 18}F-AL-NOTA-PRGD2, denoted as {sup 18}F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin αvβ3. This is a pilot study to test the safety and diagnostic value of {sup 18}F- arginine-glycine-aspartic acid (RGD) PET/computed tomography (CT) in suspected lung cancer patients. Twenty-six patients with suspected lung cancer on enhanced CT underwent {sup 18}F-alfatide RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUVs) and the tumour-to-blood ratios were measured, and diagnoses were pathologically confirmed. RGD PET/CT with {sup 18}F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed. The {sup 18}F-alfatide RGD PET/CT analysis correctly recognized 17 patients with lung cancer, 4 patients (hamartoma) as true negative, and 5 patients (4 chronic inflammation and 1 inflammatory pseudotumour) as false positive. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of {sup 18}F-alfatide RGD PET/CT for the diagnosis of suspected lung cancer patients was 100, 44.44, 80.77, 77.27, and 100 %, respectively. The area under a receiver operating characteristic (ROC) curve was 0.75 (P = 0.038), and ROC analysis suggested an SUVmax cut-off value of 2.65 to differentiate between malignant lesions and benign lesions. The SUV for malignant lesions was 5.37 ± 2.17, significantly higher than that for hamartomas (1.60 ± 0.11; P < 0.001). The difference between the tumour-to-blood ratio for malignant lesions (4.13 ± 0.91) and tissue of interest-to-blood ratio for hamartomas (1.56 ± 0.24) was also statistically significant (P < 0.001). Neither the SUVmax nor the tumour-to-blood ratio was significantly different between malignant

  1. Reproducibility study of [{sup 18}F]FPP(RGD){sub 2} uptake in murine models of human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Edwin; Liu, Shuangdong; Chin, Frederick; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Gowrishankar, Gayatri; Yaghoubi, Shahriar [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Wedgeworth, James Patrick [Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Berndorff, Dietmar; Gekeler, Volker [Bayer Schering Pharma AG, Global Drug Discovery, Berlin (Germany); Gambhir, Sanjiv S. [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Canary Center at Stanford for Cancer Early Detection, Nuclear Medicine, Departments of Radiology and Bioengineering, Molecular Imaging Program at Stanford, Stanford, CA (United States)

    2011-04-15

    An {sup 18}F-labeled PEGylated arginine-glycine-aspartic acid (RGD) dimer [{sup 18}F]FPP(RGD){sub 2} has been used to image tumor {alpha}{sub v}{beta}{sub 3} integrin levels in preclinical and clinical studies. Serial positron emission tomography (PET) studies may be useful for monitoring antiangiogenic therapy response or for drug screening; however, the reproducibility of serial scans has not been determined for this PET probe. The purpose of this study was to determine the reproducibility of the integrin {alpha}{sub v}{beta}{sub 3}-targeted PET probe, [{sup 18}F ]FPP(RGD){sub 2} using small animal PET. Human HCT116 colon cancer xenografts were implanted into nude mice (n = 12) in the breast and scapular region and grown to mean diameters of 5-15 mm for approximately 2.5 weeks. A 3-min acquisition was performed on a small animal PET scanner approximately 1 h after administration of [{sup 18}F]FPP(RGD){sub 2} (1.9-3.8 MBq, 50-100 {mu}Ci) via the tail vein. A second small animal PET scan was performed approximately 6 h later after reinjection of the probe to assess for reproducibility. Images were analyzed by drawing an ellipsoidal region of interest (ROI) around the tumor xenograft activity. Percentage injected dose per gram (%ID/g) values were calculated from the mean or maximum activity in the ROIs. Coefficients of variation and differences in %ID/g values between studies from the same day were calculated to determine the reproducibility. The coefficient of variation (mean {+-}SD) for %ID{sub mean}/g and %ID{sub max}/g values between [{sup 18}F]FPP(RGD){sub 2} small animal PET scans performed 6 h apart on the same day were 11.1 {+-} 7.6% and 10.4 {+-} 9.3%, respectively. The corresponding differences in %ID{sub mean}/g and %ID{sub max}/g values between scans were -0.025 {+-} 0.067 and -0.039 {+-} 0.426. Immunofluorescence studies revealed a direct relationship between extent of {alpha}{sub {nu}}{beta}{sub 3} integrin expression in tumors and tumor vasculature

  2. Spreading, proliferation and differentiation of human dental pulp stem cells on chitosan scaffolds immobilized with RGD or fibronectin.

    Science.gov (United States)

    Asghari Sana, Farzin; Çapkın Yurtsever, Merve; Kaynak Bayrak, Gökçe; Tunçay, Ekin Özge; Kiremitçi, Arlin S; Gümüşderelioğlu, Menemşe

    2017-08-01

    Nowadays, human dental pulp stem cells (hDPSCs) became more attractive for therapeutic purposes because of their high proliferation and differentiation potential. Thus, coupling the desired cellular characteristics of hDPSCs with good biomaterial properties of the chitosan scaffolds provide an interesting approach for tissue engineering applications. On the other hand, scaffold surface modification is also needed to promote stem cell adhesion since chitosan lacks adhesion motifs to support direct cell anchorage. In this study, hDPSCs were isolated from third molars of healthy female individuals (aged 16-25) with enzymatic digestion. For cell culture studies, the chitosan scaffolds which have approximately 9 mm diameter and 2 mm thickness with interconnected structure were prepared by freeze-drying. To support cellular attachment the scaffolds were covalently immobilized with either RGD (arginine-glycine-aspartic acid) or fibronectin (Fn) molecules. Cells were seeded on chitosan scaffolds with or without immobilized RGD and fibronectin. Cell attachment, spreading, adhesion behaviors and proliferation capacity were examined by scanning electron microscopy, immunofluorescence staining and PrestoBlue ® assays, respectively. In addition, differentiation potential of hDPSCs on Fn immobilized chitosan scaffolds was determined with real time reverse transcriptase polymerase chain reaction analysis. The results showed that chitosan scaffolds were not able to support stem cell attachment. hDPSCs on chitosan scaffolds formed spheroids more quickly and the size of spheroids were smaller than on chitosan-RGD while Fn-immobilized chitosan scaffolds strongly supported cellular attachment but not odontogenic differentiation. The results suggest that the Fn-immobilized chitosan scaffolds may serve as good three-dimensional substrates for dental pulp stem cell attachment and proliferation. In the case of dental regeneration, they must be supported by appropriate biosignals to

  3. Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yinbo Zhao

    2014-09-01

    Full Text Available In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs modified by Arg–Gly–Asp(RGD peptide, loaded with curcumin (Cur, were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid–mPEG (methoxyl poly(ethylene- glycol, RGD–polyethylene glycol (PEG–cholesterol (Chol copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD–lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD–lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD–lpNPs was increased for human umbilical vein endothelial cells (HUVEC. Furthermore, Cur loaded RGD–lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD–lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD–lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD–lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.

  4. 68Ga-BBN-RGD PET/CT for GRPR and Integrin αvβ3 Imaging in Patients with Breast Cancer.

    Science.gov (United States)

    Zhang, Jingjing; Mao, Feng; Niu, Gang; Peng, Li; Lang, Lixin; Li, Fang; Ying, Hongyan; Wu, Huanwen; Pan, Boju; Zhu, Zhaohui; Chen, Xiaoyuan

    2018-01-01

    Purpose: This study was to assess a gastrin-releasing peptide receptor (GRPR) and integrin αvβ3 dual targeting tracer 68 Ga-BBN-RGD for positron emission tomography (PET)/computed tomography (CT) imaging of breast cancer and metastasis. Materials and Methods: Twenty-two female patients were recruited either with suspected breast cancer on screening mammography (n = 16) or underwent breast cancer radical mastectomy (n = 6). All the 22 patients underwent PET/CT at 30-45 min after intravenous injection of 68 Ga-BBN-RGD. Eleven out of 22 patients also accepted 68 Ga-BBN PET/CT within 2 weeks for comparison. A final diagnosis was made based on the histopathologic examination of surgical excision or biopsy. Results: Both the primary cancer and metastases showed positive 68 Ga-BBN-RGD accumulation. The T/B ratios of 68 Ga-BBN-RGD accumulation were 2.10 to 9.44 in primary cancer and 1.10 to 3.71 in axillary lymph node metastasis, 3.80 to 10.7 in distant lymph nodes, 2.70 to 5.35 in lung metastasis and 3.17 to 22.8 in bone metastasis, respectively. For primary lesions, the SUVmax from 68 Ga-BBN-RGD PET in ER positive group was higher than that in ER negative group (P breast cancer. 68 Ga-BBN-RGD PET/CT may be of great value in discerning both primary breast cancers, axillary lymph node metastasis and distant metastases.

  5. An RGD-modified MRI-visible polymeric vector for targeted siRNA delivery to hepatocellular carcinoma in nude mice.

    Directory of Open Access Journals (Sweden)

    Chun Wu

    Full Text Available RNA interference (RNAi has significant therapeutic promise for the genetic treatment of hepatocellular carcinoma (HCC. Targeted vectors are able to deliver small interfering RNA (siRNA into HCC cells with high transfection efficiency and stability. The tripeptide arginine glycine aspartic acid (RGD-modified non-viral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (RGD-PEG-g-PEI-SPION, was constructed as a magnetic resonance imaging (MRI-visible nanocarrier for the delivery of Survivin siRNA targeting the human HCC cell line Bel-7402. The biophysical characterization of the RGD-PEG-g-PEI-SPION was performed. The RGD-modified complexes exhibited a higher transfection efficiency in transferring Survivin siRNA into Bel-7402 cells compared with a non-targeted delivery system, which resulted in more significant gene suppression at both the Survivin mRNA and protein expression levels. Then, the level of caspase-3 activation was significantly elevated, and a remarkable level of tumor cell apoptosis was induced. As a result, the tumor growth in the nude mice Bel-7402 hepatoma model was significantly inhibited. The targeting ability of the RGD-PEG-g-PEI-SPION was successfully imaged by MRI scans performed in vitro and in vivo. Our results strongly indicated that the RGD-PEG-g-PEI-SPION can potentially be used as a targeted non-viral vector for altering gene expression in the treatment of hepatocellular carcinoma and for detecting the tumor in vivo as an effective MRI probe.

  6. An RGD-Modified MRI-Visible Polymeric Vector for Targeted siRNA Delivery to Hepatocellular Carcinoma in Nude Mice

    Science.gov (United States)

    Shen, Min; Zhu, Kangshun; Cheng, Du; Liu, Zhihao; Shan, Hong

    2013-01-01

    RNA interference (RNAi) has significant therapeutic promise for the genetic treatment of hepatocellular carcinoma (HCC). Targeted vectors are able to deliver small interfering RNA (siRNA) into HCC cells with high transfection efficiency and stability. The tripeptide arginine glycine aspartic acid (RGD)-modified non-viral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (RGD-PEG-g-PEI-SPION), was constructed as a magnetic resonance imaging (MRI)-visible nanocarrier for the delivery of Survivin siRNA targeting the human HCC cell line Bel-7402. The biophysical characterization of the RGD-PEG-g-PEI-SPION was performed. The RGD-modified complexes exhibited a higher transfection efficiency in transferring Survivin siRNA into Bel-7402 cells compared with a non-targeted delivery system, which resulted in more significant gene suppression at both the Survivin mRNA and protein expression levels. Then, the level of caspase-3 activation was significantly elevated, and a remarkable level of tumor cell apoptosis was induced. As a result, the tumor growth in the nude mice Bel-7402 hepatoma model was significantly inhibited. The targeting ability of the RGD-PEG-g-PEI-SPION was successfully imaged by MRI scans performed in vitro and in vivo. Our results strongly indicated that the RGD-PEG-g-PEI-SPION can potentially be used as a targeted non-viral vector for altering gene expression in the treatment of hepatocellular carcinoma and for detecting the tumor in vivo as an effective MRI probe. PMID:23922634

  7. Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography

    Science.gov (United States)

    Schnell, Oliver; Krebs, Bjarne; Carlsen, Janette; Miederer, Isabelle; Goetz, Claudia; Goldbrunner, Roland H.; Wester, Hans-Jürgen; Haubner, Roland; Pöpperl, Gabriele; Holtmannspötter, Markus; Kretzschmar, Hans A.; Kessler, Horst; Tonn, Jörg-Christian; Schwaiger, Markus; Beer, Ambros J.

    2009-01-01

    Inhibitors targeting the integrin αvβ3 are promising new agents currently tested in clinical trials for supplemental therapy of glioblastoma multiforme (GBM). The aim of our study was to evaluate 18F-labeled glycosylated Arg-Gly-Asp peptide ([18F]Galacto-RGD) PET for noninvasive imaging of αvβ3 expression in patients with GBM, suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [18F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor hotspots, galea, and blood pool were derived by region-of-interest analysis. [18F]Galacto-RGD PET images were fused with cranial MR images for image-guided surgery. Tumor samples taken from areas with intense tracer accumulation in the [18F]Galacto-RGD PET images and were analyzed histologically and immunohistochemically for αvβ3 integrin expression. While normal brain tissue did not show significant tracer accumulation (mean SUV, 0.09 ± 0.04), GBMs demonstrated significant but heterogeneous tracer uptake, with a maximum in the highly proliferating and infiltrating areas of tumors (mean SUV, 1.6 ± 0.5). Immunohistochemical staining was prominent in tumor microvessels as well as glial tumor cells. In areas of highly proliferating glial tumor cells, tracer uptake (SUVs) in the [18F]Galacto-RGD PET images correlated with immunohistochemical αvβ3 integrin expression of corresponding tumor samples. These data suggest that [18F] Galacto-RGD PET successfully identifies αvβ3 expression in patients with GBM and might be a promising tool for planning and monitoring individualized cancer therapies targeting this integrin. PMID:19401596

  8. Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography.

    Science.gov (United States)

    Schnell, Oliver; Krebs, Bjarne; Carlsen, Janette; Miederer, Isabelle; Goetz, Claudia; Goldbrunner, Roland H; Wester, Hans-Jürgen; Haubner, Roland; Pöpperl, Gabriele; Holtmannspötter, Markus; Kretzschmar, Hans A; Kessler, Horst; Tonn, Jörg-Christian; Schwaiger, Markus; Beer, Ambros J

    2009-12-01

    Inhibitors targeting the integrin alpha(v)beta(3) are promising new agents currently tested in clinical trials for supplemental therapy of glioblastoma multiforme (GBM). The aim of our study was to evaluate (18)F-labeled glycosylated Arg-Gly-Asp peptide ([(18)F]Galacto-RGD) PET for noninvasive imaging of alpha(v)beta(3) expression in patients with GBM, suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [(18)F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor hotspots, galea, and blood pool were derived by region-of-interest analysis. [(18)F]Galacto-RGD PET images were fused with cranial MR images for image-guided surgery. Tumor samples taken from areas with intense tracer accumulation in the [(18)F]Galacto-RGD PET images and were analyzed histologically and immunohistochemically for alpha(v)beta(3) integrin expression. While normal brain tissue did not show significant tracer accumulation (mean SUV, 0.09 +/- 0.04), GBMs demonstrated significant but heterogeneous tracer uptake, with a maximum in the highly proliferating and infiltrating areas of tumors (mean SUV, 1.6 +/- 0.5). Immunohistochemical staining was prominent in tumor microvessels as well as glial tumor cells. In areas of highly proliferating glial tumor cells, tracer uptake (SUVs) in the [(18)F]Galacto-RGD PET images correlated with immunohistochemical alpha(v)beta(3) integrin expression of corresponding tumor samples. These data suggest that [(18)F] Galacto-RGD PET successfully identifies alpha(v)beta(3) expression in patients with GBM and might be a promising tool for planning and monitoring individualized cancer therapies targeting this integrin.

  9. Cell-Adhesive Matrices Composed of RGD Peptide-Displaying M13 Bacteriophage/Poly(lactic-co-glycolic acid) Nanofibers Beneficial to Myoblast Differentiation.

    Science.gov (United States)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Kim, Chuntae; Hong, Suck Won; Oh, Jin Woo; Han, Dong-Wook

    2015-10-01

    Recently, there has been considerable effort to develop suitable scaffolds for tissue engineering applications. Cell adhesion is a prerequisite for cells to survive. In nature, the extracellular matrix (ECM) plays this role. Therefore, an ideal scaffold should be structurally similar to the natural ECM and have biocompatibility and biodegradability. In addition, the scaffold should have biofunctionality, which provides the potent ability to enhance the cellular behaviors, such as adhesion, proliferation and differentiation. This study concentrates on fabricating cell-adhesive matrices composed of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) nanofibers. Long rod-shaped M13 bacteriophages are non-toxic and can express many desired proteins on their surface. A genetically engineered M13 phage was constructed to display RGD peptides on its surface. PLGA is a biodegradable polymer with excellent biocompatibility and suitable physicochemical property for adhesive matrices. In this study, RGD-M13 phage/PLGA hybrid nanofiber matrices were fabricated by electrospinning. The physicochemical properties of these matrices were characterized by scanning electron microscopy, atomic force microscopy, Raman spectroscopy, and contact angle measurement. In addition, the cellular behaviors, such as the initial attachment, proliferation and differentiation, were analyzed by a CCK-8 assay and immunofluorescence staining to evaluate the potential application of these matrices to tissue engineering scaffolds. The RGD-M13 phage/PLGA nanofiber matrices could enhance the cellular behaviors and promote the differentiation of C2C12 myoblasts. These results suggest that the RGD-M13 phage/PLGA nanofiber matrices are beneficial to myoblast differentiation and can serve as effective tissue engineering scaffolds.

  10. In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

    Directory of Open Access Journals (Sweden)

    Yin Hong

    2011-06-01

    Full Text Available Abstract Background Foot-and-mouth disease virus (FMDV uses a highly conserved Arg-Gly-Asp (RGD triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05 and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD or an Arg-Ser-Asp (RSD triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals. Results Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that

  11. The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Lotte M E Berghauser Pont

    Full Text Available A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastoma-pathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delta24-RGD. HDAC inhibitors (HDACi affect integrins and share common cell death pathways with Delta24-RGD. We studied the combination treatment effects of HDACi and Delta24-RGD in patient-derived glioblastoma stem-like cells (GSC, and we determined the most effective HDACi.SAHA, Valproic Acid, Scriptaid, MS275 and LBH589 were combined with Delta24-RGD in fourteen distinct GSCs. Synergy was determined by Chou Talalay method. Viral infection and replication were assessed using luciferase and GFP encoding vectors and hexon-titration assays. Coxsackie adenovirus receptor and αvβ3 integrin levels were determined by flow cytometry. Oncolysis and mechanisms of cell death were studied by viability, caspase-3/7, LDH and LC3B/p62, phospho-p70S6K. Toxicity was studied on normal human astrocytes. MGMT promotor methylation status, TCGA classification, Rb-pathway and integrin gene expression levels were assessed as markers of responsiveness.Scriptaid and LBH589 acted synergistically with Delta24-RGD in approximately 50% of the GSCs. Both drugs moderately increased αvβ3 integrin levels and viral infection in responding but not in non-responding GSCs. LBH589 moderately increased late viral gene expression, however, virus titration revealed diminished viral progeny production by both HDACi, Scriptaid augmented caspase-3/7 activity, LC3B conversion, p62 and phospho-p70S6K consumption, as well as LDH levels. LBH589 increased LDH and phospho-p70S6K consumption. Responsiveness correlated with expression of various Rb-pathway genes and integrins. Combination treatments induced limited toxicity to human astrocytes.LBH589 and Scriptaid combined with Delta24-RGD revealed synergistic anti

  12. Theranostics of Triple-Negative Breast Cancer Based on Conjugated Polymer Nanoparticles.

    Science.gov (United States)

    Jin, Guorui; He, Rongyan; Liu, Qian; Dong, Yuqing; Lin, Min; Li, Wenfang; Xu, Feng

    2018-04-04

    Triple-negative breast cancer (TNBC) does not respond to many targeted drugs due to the lack of three receptors (i.e., estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2), which makes it difficult for TNBC detection and treatment. As compared to traditional breast cancer treatments such as surgery and chemotherapy, photodynamic therapy (PDT) has emerged as a promising approach for treating TNBC due to its precise controllability, high spatiotemporal accuracy, and minimal invasive nature. However, traditional photosensitizers used in PDT are associated with limitations of aggregation-caused quenching (ACQ), and the ACQ induced a significant decrease in reactive oxygen species (ROS) generation. To address these, we synthesized a cyclic arginine-glycine-aspartic acid (cRGD) peptide-decorated conjugated polymer (CP) nanoparticles with poly[2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylenevinylene] (MEH-PPV) as the photosensitizer for the theranostics of TNBC. The synthesized CP nanoparticles show bright fluorescence with high stability and could effectively produce ROS under light irradiation. Cell viability studies showed that the CP nanoparticles have negligible dark cytotoxicity and could efficiently kill the α v β 3 integrin-overexpressed MDA-MB-231 cells (one subtype of TNBC cells) in a selective way. With the use of cRGD-modified MEH-PPV nanoparticles as the theranostic agent, it permits targeted imaging and PDT of TNBC both in the in vitro 3D tumor model and in living mice. The application of CP nanoparticles in the successful theranostics of TNBC could pave the way for future development of CP-based photosensitizers for clinical applications.

  13. Molecular nuclear imaging of tumoral angio genesis using a rgd-containing tracer, Raft-RGD, targeted at the neo vessel-specific integrin {alpha}{sub v}{beta}{sub 3}; Evaluation d'un radioligand de l'integrine {alpha}{sub v}{beta}{sub 3} (RAFT-RGD) pour l'imagerie moleculaire de l'angiogenese tumorale

    Energy Technology Data Exchange (ETDEWEB)

    Sancey, L

    2006-06-15

    Tumoral neo-angio genesis targeting is currently a major field of research for the diagnostic and treatment of solid tumors. Endothelial cells from neo vessels over express several specific markers such as the {alpha}{sub v}{beta}{sub 3} integrin, which binds RGD (-Arg-Gly-Asp-)- containing peptides. We evaluated the potential of a novel radiotracer - RAFT-RGD - for the molecular nuclear imaging of neo vessels. In vitro, the coupling of 4 c(RGDfK) to the RAFT platform resulted in an increased cellular uptake of the tracer by {alpha}{sub v}{beta}{sub 3} positive cells when compared to c(RGDfK). Furthermore, RAFTRGD has a higher affinity than c(RGDfK) and similar properties for angio genesis inhibition. In vivo, both {alpha}{sub v}{beta}{sub 3} positive and negative tumors were visible by non invasive whole body planar and tomographic imaging from 30 min to 24 h post-injection, using a gamma camera dedicated to small animal imaging. Despite a lack of significant contrast improvement compare with c(RGDfK), RAFT-RGD could represent a promising tracer for tumoral angio genesis since it could provide invaluable information about tumor development and treatment efficacy in Nuclear Medicine departments. Furthermore, thanks to its chemical structure, RAFT-RGD can be labelled with a variety of radioisotopes including {gamma} and {beta}{sup -} emitters, allowing interesting therapeutical applications such as internal targeted radiotherapy. (author)

  14. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  15. Pharmacokinetics of 99m Tc-EDDA/HYNIC-Lys-D-Phe-RGD in athymic mice with induced malignant tumors for integrin imaging

    International Nuclear Information System (INIS)

    Lopez D, F.A.; Pedraza L, M.; Murphy, C.A. de; Ferro F, G.; Hernandez H, E.

    2007-01-01

    Full text: Nuclear medicine imaging techniques are non-invasive and monitor the spatiotemporal distribution of molecular events. Radiolabeled RGD-peptides are currently investigated to target integrin receptors for in vivo tumor imaging. The α v β 3 integrin is a target structure involved in the angio genesis process which mediates the binding to extracellular matrix via different proteins such as vitronectin, fibronectin and von Willebrand factor. The aim of this research was to prepare [ 99m Tc]-Lys-D-Phe-RGD and to evaluate its pharmacokinetics in athymic mice with three different induced malignant tumors. Tumor uptake values of 99m Tc-Lys-D-Phe-RGD labeled via HYNIC and EDDA showed good ability to target α v β 3 integrin receptors in the three different kinds of tumors (breast, prostate and neuroendocrine). A high in vivo stability and favorable pharmacokinetic properties such as fast blood clearance, rapid renal excretion, low liver and muscle uptake and low intestinal excretion were observed. This study demonstrated that 99m Tc-EDDA/HYNIC-Lys-D-Phe-RGD is a specific and potential radiopharmaceutical to image α v β 3 integrin receptors in a variety of tumors. (Author)

  16. Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces

    NARCIS (Netherlands)

    Sankaran, Shrikrishnan; Cavatorta, Emanuela; Huskens, Jurriaan; Jonkheijm, Pascal

    2017-01-01

    Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form

  17. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with 177Lu and evaluation in vitro and in vivo stability

    International Nuclear Information System (INIS)

    Vilchis J, A.

    2010-01-01

    Integrin αvβ3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the αvβ3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with 177 Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of 177 LuCl 3 with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90 o C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive αvβ3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. 177 Lu-DOTA-RGD and 177 Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to □ v □ 3 receptors. (Author)

  18. PET imaging of alpha(v)beta(3) integrin expression in tumours with Ga-68-labelled mono-, di- and tetrameric RGD peptides

    NARCIS (Netherlands)

    Dijkgraaf, Ingrid; Yim, Cheng-Bin; Franssen, Gerben M.; Schuit, Robert C.; Luurtsema, Gert; Liu, Shuang; Oyen, Wim J. G.; Boerman, Otto C.

    Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of Ga-68-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their

  19. Electrochromic in conjugated polymers

    International Nuclear Information System (INIS)

    Picado Valenzuela, Alfredo

    2007-01-01

    This revision considered object the description of one of the materials with the greatest potential in the field of electrochromic (mainly in the visible region): the conjugated polymers (CP), area of enormous potential both now and in a short time ahead. The CP are insulating materials and organic semiconductors in a state not doped. They can be doped positively or negatively being observed a significant increase in the conductivity and being generated a color change in these materials. The understanding of how optical properties vary based on the chemical structure of the polymer or its mixtures and more precisely of the alternatives that can be entered into the conjugated system or π system to obtain a material that besides to be flexible, environmentally stable, presents the colored states. The revision was centred chiefly in the polypyrrole (Ppy), the polythiophene (PTh) and their derivatives such as poly (3.4-ethylenedioxythiophene) (PEDOT). The advantage of using monomers with variable structure, to adjust the composition of the copolymer, or to blend with the PC, allows to obtain a variety of colored states that can be modulated through the visible spectrum and even with applications to wavelengths outside of this region. Because the PC presented at least two different colored states can be varied continuously as a function of the voltage applied. In some cases, they may submit multicoloured statements, which offers a range of possibilities for their application in flexible electronic devices type screens and windows. Applications include smart windows, camouflage clothing and data screens. This type of material is emerging as one of the substitutes of the traditional inorganic semiconductor, with the advantage of its low cost, high flexibility and the possibility to generate multiple colors through the handling of the monomers in the structure and control of energy of his band gap. (author) [es

  20. Generalized conjugate gradient squared

    Energy Technology Data Exchange (ETDEWEB)

    Fokkema, D.R.; Sleijpen, G.L.G. [Utrecht Univ. (Netherlands)

    1994-12-31

    In order to solve non-symmetric linear systems of equations, the Conjugate Gradient Squared (CGS) is a well-known and widely used iterative method. In practice the method converges fast, often twice as fast as the Bi-Conjugate Gradient method. This is what you may expect, since CGS uses the square of the BiCG polynomial. However, CGS may suffer from its erratic convergence behavior. The method may diverge or the approximate solution may be inaccurate. BiCGSTAB uses the BiCG polynomial and a product of linear factors in an attempt to smoothen the convergence. In many cases, this has proven to be very effective. Unfortunately, the convergence of BiCGSTAB may stall when a linear factor (nearly) degenerates. BiCGstab({ell}) is designed to overcome this degeneration of linear factors. It generalizes BiCGSTAB and uses both the BiCG polynomial and a product of higher order factors. Still, CGS may converge faster than BiCGSTAB or BiCGstab({ell}). So instead of using a product of linear or higher order factors, it may be worthwhile to look for other polynomials. Since the BiCG polynomial is based on a three term recursion, a natural choice would be a polynomial based on another three term recursion. Possibly, a suitable choice of recursion coefficients would result in method that converges faster or as fast as CGS, but less erratic. It turns out that an algorithm for such a method can easily be formulated. One particular choice for the recursion coefficients leads to CGS. Therefore one could call this algorithm generalized CGS. Another choice for the recursion coefficients leads to BiCGSTAB. It is therefore possible to mix linear factors and some polynomial based on a three term recursion. This way one may get the best of both worlds. The authors will report on their findings.

  1. In-depth evaluation of the cycloaddition--retro-Diels--Alder reaction for in vivo targeting with [(111)In]-DTPA-RGD conjugates.

    NARCIS (Netherlands)

    Laverman, P.; Meeuwissen, S.A.; Berkel, S.S. van; Oyen, W.J.G.; Delft, F.L. van; Rutjes, F.P.J.T.; Boerman, O.C.

    2009-01-01

    INTRODUCTION: The spontaneous copper-free tandem 1,3-dipolar cycloaddition-retro-Diels-Alder (tandem crDA) reaction between cyclic Arg-Gly-Asp-d-Phe-Orn(N(3)) [c(RGDfX)] and oxanorbornadiene-DTPA (o-DTPA) or methyloxanorbornadiene-DTPA (mo-DTPA) into two DTPA-c(RGDfX) regioisomers is characterized.

  2. Reciprocity and conjugation fidelity in double phase conjugate mirrors

    Science.gov (United States)

    Delaye, Philippe; Fotiadi, Andrei A.; Roosen, Gerald

    1999-09-01

    It is well known that the conservation of energy in an optical system can be described by an invariant (intensity of the optical wave) during propagation. We identically show that reciprocity can be described by an invariant. This invariant is the overlap integral of two counterpropagating waves, that stays constant in every place of a reciprocal optical system. Applied to the double phase conjugate mirror (DPCM) this invariant can be rewritten as an equality between the ratio of the conjugation fidelity of the two ports of the DPCM and the ratio of the transmission in intensity of the two beams. If restricted to a plane wave case this relation becomes the well known equality of the diffraction efficiencies in both directions. We have implemented an experimental set-up that allows to show that the double phase conjugate mirror is reciprocal what confirms all the above discussion. We use the same set-up to measure the conjugation fidelity of the DPCM.

  3. Fluorescence lifetime imaging to differentiate bound from unbound ICG-cRGD both in vitro and in vivo

    Science.gov (United States)

    Stegehuis, Paulien L.; Boonstra, Martin C.; de Rooij, Karien E.; Powolny, François E.; Sinisi, Riccardo; Homulle, Harald; Bruschini, Claudio; Charbon, Edoardo; van de Velde, Cornelis J. H.; Lelieveldt, Boudewijn P. F.; Vahrmeijer, Alexander L.; Dijkstra, Jouke; van de Giessen, Martijn

    2015-03-01

    Excision of the whole tumor is crucial, but remains difficult for many tumor types. Fluorescence lifetime imaging could be helpful intraoperative to differentiate normal from tumor tissue. In this study we investigated the difference in fluorescence lifetime imaging of indocyanine green coupled to cyclic RGD free in solution/serum or bound to integrins e.g. in tumors. The U87-MG glioblastoma cell line, expressing high integrin levels, was cultured to use in vitro and to induce 4 subcutaneous tumors in a-thymic mice (n=4). Lifetimes of bound and unbound probe were measured with an experimental time-domain single-photon avalanche diode array (time resolution bound probe compared to unbound probe. In vivo, lifetimes of the fluorophores in tumors were significantly higher (pbound and unbound probes in vivo.

  4. Sequential measurements of conjugate observables

    Energy Technology Data Exchange (ETDEWEB)

    Carmeli, Claudio [Dipartimento di Fisica, Universita di Genova, Via Dodecaneso 33, 16146 Genova (Italy); Heinosaari, Teiko [Department of Physics and Astronomy, Turku Centre for Quantum Physics, University of Turku, 20014 Turku (Finland); Toigo, Alessandro, E-mail: claudio.carmeli@gmail.com, E-mail: teiko.heinosaari@utu.fi, E-mail: alessandro.toigo@polimi.it [Dipartimento di Matematica ' Francesco Brioschi' , Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2011-07-15

    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  5. Protein carriers of conjugate vaccines

    Science.gov (United States)

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  6. Conjugated Fatty Acid Synthesis

    Science.gov (United States)

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-01-01

    Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

  7. Research study of conjugate materials; Conjugate material no chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.

  8. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with {sup 177}Lu and evaluation in vitro and in vivo stability; Radiomarcado del peptido c-DOTA-RGD y c-DOTA-RGDf con {sup 177}Lu y evaluacion de su estabilidad in vitro e in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2010-07-01

    Integrin {alpha}v{beta}3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the {alpha}v{beta}3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with {sup 177}Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of {sup 177}LuCl{sub 3} with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90{sup o} C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive {alpha}v{beta}3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. {sup 177}Lu-DOTA-RGD and {sup 177}Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to {open_square}{sub v}{open_square}{sub 3} receptors. (Author)

  9. Conjugated polymer nanoparticles, methods of using, and methods of making

    KAUST Repository

    Habuchi, Satoshi

    2017-03-16

    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  10. Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.

    Science.gov (United States)

    Quinn, T J; Healy, N; Sara, A; Maggi, E; Claros, C S; Kabarriti, R; Scandiuzzi, L; Liu, L; Gorecka, J; Adem, A; Basu, I; Yuan, Z; Guha, C

    2017-01-01

    The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

  11. An improved method of 18F peptide labeling: hydrazone formation with HYNIC-conjugated c(RGDyK)

    International Nuclear Information System (INIS)

    Lee, Yun-Sang; Jeong, Jae Min; Kim, Hyung Woo; Chang, Young Soo; Kim, Young Joo; Hong, Mee Kyung; Rai, Ganesha B.; Chi, Dae Yoon; Kang, Won Jun; Kang, Joo Hyun; Lee, Dong Soo; Chung, June-Key; Lee, Myung Chul; Suh, Young-Ger

    2006-01-01

    Radiolabeled α v β 3 -integrin antagonists are increasingly investigated as a means of imaging angiogenesis. Several methods of labeling α v β 3 -integrin binding peptide with 18 F have been reported recently. In the present study, we devised a straightforward means for labeling Arg-Gly-Asp (RGD) peptide with 18 F via hydrazone formation between c(RGDyK)-hydrazinonicotinic acid (HYNIC) (3) and 4-[ 18 F]-fluorobenzaldehyde ([ 18 F]4). The resulting reaction mixture was purified by HPLC to give 4'-[ 18 F]-fluorobenzylidenehydrazone-6-nicotinamide-c(RGDyK) ([ 18 F]5). The conjugation efficiency of 3 and 4 to form [ 18 F]5 was 95.2%, and the radiochemical purity of [ 18 F]5 after purification was >99%. The specific activity of [ 18 F]5 estimated by radio-HPLC was 20.5 GBq/μmol (end of synthesis). Competitive binding assay of c(RGDyK) (1) and 5 was performed using [ 125 I]iodo-c(RGDyK) as a radioligand, and K i values were found to be 2.8 and 21.7 nM, respectively. For the biodistribution study, the angiogenic mouse model was established by inducing unilateral ischemia on the left hindlimbs of ICR mice after femoral artery ablation. Seven days after inducing ischemia, [ 18 F]5 was administered to the mice through the tail vein. Ischemic muscle uptake of [ 18 F]5 was significantly higher than that of normal muscle (P 18 F]5. Here, we successfully labeled RGD peptide with 18 F via hydrazone formation between 3 and 4, resulting to [ 18 F]5. [ 18 F]5 was found to have high affinity for α v β 3 -integrin and to accumulate specifically in ischemic hindlimb muscle of mice. We suggest that 18 F labeling via formation of hydrazone between HYNIC peptide and [ 18 F]4 is a useful method for labeling c(RGDyK), which can be applied for imaging angiogenesis

  12. Antibody Drug Conjugates: Preclinical Considerations.

    Science.gov (United States)

    Bornstein, Gadi G

    2015-05-01

    The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted.

  13. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    maintenance in the host cell. These importantly include the ability to self-mobilize in a process termed conjugative transfer, which may occur across species barriers. Other plasmid stabilizing mechanisms include the multimer resolution system, active partitioning, and post-segregational-killing of plasmid......Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting...... the successful propagation and long-term continued existence of these extra-chromosomal elements is extensive. Apart from the accessory genetic elements that may provide plasmid-harboring cells a selective advantage, special focus is placed on the mechanisms conjugative plasmids employ to ensure their stable...

  14. Buried, covalently attached RGD peptide motifs in poly(methacrylic acid) brush layers: the effect of brush structure on cell adhesion.

    Science.gov (United States)

    Navarro, Melba; Benetti, Edmondo M; Zapotoczny, Szczepan; Planell, Josep A; Vancso, G Julius

    2008-10-07

    Iniferter-mediated surface-initiated photopolymerization was used to graft poly(methacrylic acid) (PMAA) brush layers obtained from surface-attached iniferters in self-assembled monolayers to a gold surface. The tethered chains were subsequently functionalized with the cell-adhesive arginine-glycine-aspartic acid (RGD) motif. The modified brushes were extended by reinitiating the polymerization to obtain an additional layer of PMAA, thereby burying the peptide-functionalized segments inside the brush structure. Contact angle measurements and Fourier transform infrared (FTIR) spectroscopy were employed to characterize the wettability and the chemical properties of these platforms. Time of flight secondary ion mass spectroscopy (TOF-SIMS) measurements were performed to monitor the chemical composition of the polymer layer as a function of the distance to the gold surface and obtain information concerning the depth of the RGD motifs inside the brush structure. The brush thickness was evaluated as a function of the polymerization (i.e., UV-irradiation) time with atomic force microscopy (AFM) and ellipsometry. Cell adhesion tests employing human osteoblasts were performed on substrates with the RGD peptides exposed at the surface as well as covered by a PMAA top brush layer. Immunofluorescence studies demonstrated a variation of the cell morphology as a function of the position of the peptide units along the grafted chains.

  15. Phase conjugation of acoustic beams

    Science.gov (United States)

    Bunkin, F. V.; Vlasov, D. V.; Kravtsov, Iu. A.

    The paper presents a classification of methods for the phase conjugation (PC) of wave fields of various physical natures on the basis of such nonliner interactions as stimulated scattering, and three- and four-wave interactions. Among the latter, attention is given to holographic (volume and surface) and parametric PC schemes, permitting PC with amplification. The possibility of developing phase-conjugated devices using acoustic PC devices on the basis of various nonlinear effects is considered. Experimental results pertaining to the PC of sound fields are presented, and possible applications of acoustic PC devices are indicated.

  16. High pressure structural studies of conjugated molecules

    DEFF Research Database (Denmark)

    Knaapila, Matti; Torkkeli, Mika; Scherf, Ullrich

    2018-01-01

    This chapter highlights high pressure GPa level structural studies of conjugated polymers and their analogues: conjugated oligomers and molecules, and rigid rod polymers. Attention is placed on our recent studies of polyfluorenes.......This chapter highlights high pressure GPa level structural studies of conjugated polymers and their analogues: conjugated oligomers and molecules, and rigid rod polymers. Attention is placed on our recent studies of polyfluorenes....

  17. An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA

    Directory of Open Access Journals (Sweden)

    Jens eConradi

    2012-05-01

    Full Text Available Helicobacter pylori is a specific gastric pathogen that colonizes the stomach in more than 50% of the world’s human population. Infection with this bacterium can induce several types of gastric pathology, ranging from chronic gastritis to peptic ulcers and even adenocarcinoma. Virulent H. pylori isolates encode components of a type IV secretion system (T4SS, which form a pilus for the injection of virulence proteins such as CagA into host target cells. This is accomplished by a specialized adhesin on the pilus surface, the protein CagL, a putative VirB5 ortholog, which binds to host cell β1 integrin, triggering subsequent delivery of CagA across the host cell membrane. Like the human extracellular matrix protein fibronectin, CagL contains an RGD (Arg-Gly-Asp motif and is able to trigger intracellular signaling pathways by RGD-dependent binding to integrins. While CagL binding to host cells is mediated primarily by the RGD motif, we identified an auxiliary binding motif for CagL-integrin interaction. Here, we report on a surface-exposed FEANE (Phe-Glu-Ala-Asn-Glu interaction motif in spatial proximity to the RGD sequence, which enhances the interactions of CagL with integrins. It will be referred to as RGD helper sequence (RHS. Competitive cell adhesion assays with recombinant wild type CagL and point mutants, competition experiments with synthetic cyclic and linear peptides, and peptide array experiments revealed amino acids essential for the interaction of the RHS motif with integrins. Infection experiments indicate that the RHS motif plays a role in the early interaction of H. pylori T4SS with integrin, to trigger signaling and to inject CagA into host cells. We thus postulate that CagL is a versatile T4SS surface protein equipped with at least two motifs to promote binding to integrins, thereby causing aberrant signaling within host cells and facilitating translocation of CagA into host cells, thus contributing directly to H. pylori

  18. Enhanced photophysics of conjugated polymers

    Science.gov (United States)

    Chen, Liaohai [Darien, IL

    2007-06-12

    A particulate fluorescent conjugated polymer surfactant complex and method of making and using same. The particles are between about 15 and about 50 nm and when formed from a lipsome surfactant have a charge density similar to DNA and are strongly absorbed by cancer cells.

  19. Conjugal Pairing in Escherichia Coli

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 8. Conjugal Pairing in Escherichia Coli. Joshua Lederberg. Classics Volume 13 Issue 8 August 2008 pp 793-794. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/013/08/0793-0794 ...

  20. Galois conjugates of topological phases

    Science.gov (United States)

    Freedman, M. H.; Gukelberger, J.; Hastings, M. B.; Trebst, S.; Troyer, M.; Wang, Z.

    2012-01-01

    Galois conjugation relates unitary conformal field theories and topological quantum field theories (TQFTs) to their nonunitary counterparts. Here we investigate Galois conjugates of quantum double models, such as the Levin-Wen model. While these Galois-conjugated Hamiltonians are typically non-Hermitian, we find that their ground-state wave functions still obey a generalized version of the usual code property (local operators do not act on the ground-state manifold) and hence enjoy a generalized topological protection. The key question addressed in this paper is whether such nonunitary topological phases can also appear as the ground states of Hermitian Hamiltonians. Specific attempts at constructing Hermitian Hamiltonians with these ground states lead to a loss of the code property and topological protection of the degenerate ground states. Beyond this, we rigorously prove that no local change of basis can transform the ground states of the Galois-conjugated doubled Fibonacci theory into the ground states of a topological model whose Hermitian Hamiltonian satisfies Lieb-Robinson bounds. These include all gapped local or quasilocal Hamiltonians. A similar statement holds for many other nonunitary TQFTs. One consequence is that these nonunitary TQFTs do not describe physical realizations of topological phases. In particular, this implies that the “Gaffnian” wave function can not be the ground state of a gapped fractional quantum Hall state.

  1. Conjugal Pairing in Escherichia Coli

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 8. Conjugal Pairing in Escherichia Coli. Joshua Lederberg. Classics Volume 13 Issue 8 August 2008 pp 793-794. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/013/08/0793-0794 ...

  2. Bacteriophytochromes control conjugation in Agrobacterium fabrum.

    Science.gov (United States)

    Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman

    2016-08-01

    Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy ...

    African Journals Online (AJOL)

    REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...

  4. A physics-explicit model of bacterial conjugation shows the stabilizing role of the conjugative junction

    OpenAIRE

    Pastuszak, Jakub; Waclaw, Bartlomiej

    2017-01-01

    Conjugation is a process in which bacteria exchange DNA through a physical connection (conjugative junction) between mating cells. Despite its significance for processes such as the spread of antibiotic resistance, the role of physical forces in conjugation is poorly understood. Here we use computer models to show that the conjugative junction not only serves as a link to transfer the DNA but it also mechanically stabilises the mating pair which significantly increases the conjugation rate. W...

  5. A novel synthetic peptide polymer with cyclic RGD motifs supports serum-free attachment of anchorage-dependent cells.

    Science.gov (United States)

    Markó, K; Ligeti, M; Mezo, G; Mihala, N; Kutnyánszky, E; Kiss, E; Hudecz, F; Madarász, E

    2008-09-01

    Cell adhesivity is a basic biological principle, which provides mechanisms for construction of multicellular organisms, tissue genesis, migration and individual cell survival. In vivo, the cell adhesive environment is provided by extracellular matrix molecules, neighboring cell surfaces and soluble factors delivered either by tissue cells or by blood circulation. The exact molecular composition of the microenvironment of a cell is not properly understood. The nondefined molecular composition of "native" adhesive components hinders their application when defined culture conditions are necessary, as, for an example, growing human cells for further clinical application. Applying large, substrate-coating molecules as backbones for carrying specific adhesive peptide motifs provides a relatively cheap, reproducible, and chemically defined group of synthetic adhesion molecules. Here, we report on the design, synthesis, and testing of a novel cyclic RGD-containing coating material, which promotes initial attachment, spreading, survival, and proliferation of a number of different cell types. The potent adhesive polypeptide-brush, composed of poly[Lys(DL-Ala(m))] branched chain polypeptide (AK) and multiple copies of cyclic(arginyl-glycyl-aspartyl-D-phenylalanyl-cysteine) pentapeptide prevents anoikis and supports cell attachment in the absence of serum or other biological additives. The defined conditions for cell maintenance make this material a promising candidate for coating artificial cell substrates even for therapeutic applications.

  6. TAT Peptide and Its Conjugates: Proteolytic Stability

    OpenAIRE

    Grunwald, Jacob; Rejtar, Tomas; Sawant, Rupa; Wang, Zhouxi; Torchilin, Vladimir P.

    2009-01-01

    The proteolytic cleavage of TATp, TATp-PEG1000-PE conjugate (TATp-conjugate), and TATp as TATp-conjugate in mixed micelles made of TATp-conjugate and PEG5000-PE (2.5% mol of TATp-conjugate, TATp-Mic) were studied by HPLC with fluorescent detection using fluorenylmethyl chloroformate (FMOC) labeling and by MALDI-TOF MS analysis. The cleavage kinetics were analyzed in human blood plasma and in trypsin-containing phosphate buffered saline (PBS), pH 7.4, to simulate the proteolytic activity of hu...

  7. Conjugated Polymers for Energy Production

    DEFF Research Database (Denmark)

    Livi, Francesco

    for scalable PSCs fully printed under ambient conditions [Adv. Energy Mater. 2015, 5, 1402186]. PPDTBT resulted to be the conjugated polymer with the best photovoltaic performance within the 104 synthesized macromolecules. Therefore, further studies have been done on such material. The impact of side chain......This dissertation is aimed at developing materials for flexible, large area, ITO-free polymer solar cells (PSCs) fully printed under ambient conditions. A large screening of conjugated polymers, both novel and well-known materials, has been carried out in order to find suitable candidates.......The reactivity of DArP has been further studied and applied to the synthesis of fluorinated copolymers featuring thiophene, which are largely used materials for organic electronics. In particular, by moving the bromine functionality from one monomer to the other, a big impact on the reactivity has been observed...

  8. Organometallic B12-DNA conjugate

    DEFF Research Database (Denmark)

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander

    2014-01-01

    Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets...... with transcobalamin (TC), but not so efficient with the homologous glycoproteins intrinsic factor and haptocorrin. Binding of the B12 octadecanucleotide to TC suggests the capacity of the B12 moiety to serve as a natural vector for specific transport of single stranded, organometallic oligonucleotide loads from...... in humans and animals, through the endogenous B12 transport systems. Binding of the organometallic B12 octadecanucleotide to the three important human proteins of B12 transport was studied, to examine its structural suitability for the task of eventual in vivo oligonucleotide delivery. Binding was efficient...

  9. Characterization of a fusion protein of RGD4C and the ß-lactamase variant for antibody-directed enzyme prodrug therapy

    Directory of Open Access Journals (Sweden)

    Zhou XL

    2014-04-01

    Full Text Available Xiaoliang Zhou, Hao Wang, Peiji Shi, Ai-min MengInstitute of Radiation Medicine, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, People's Republic of ChinaAbstract: Antibody-directed enzyme prodrug therapy (ADEPT delivers chemotherapeutic agents in high concentration to tumor tissue, while minimizing systemic drug exposure. ADEPT has been reported to be an attractive approach for improving the efficacy of cancer therapy. A previously reported β-lactamase was found to contain four cluster of differentiation (CD4+ T cell epitopes; however, single amino acid changes in the enzyme resulted in significantly reduced proliferative responses, while retaining stability and activity of the enzyme. The β-lactamase variant with reduced immunogenicity is an attractive alternative for constructing the ADEPT fusion protein. In this study, we fused the peptide, RGD4C, known to target integrin αvβ3, to the β-lactamase variant for use in ADEPT. Biological function studies revealed that RGD4C- β-lactamase had a high hydrolytic effect on nitrocefin and cephalosporin–melphalan, and high plasma stability was observed. In addition, fusion of the RGD4C moiety to β-lactamase had little effect on immunogenicity compared with β-lactamase in the proliferation of peripheral blood mononuclear cells. The ability of this fusion protein to both target the central region of αvβ3 and induce toxicity in the non-small-cell lung cancer cell NCI-H460 makes it a promising therapeutic approach in the treatment of cancer.Keywords: ADEPT, immunogenicity, integrinαvβ3

  10. Biokinetics and dosimetry of a hybrid formulation of 9mTc-BN and 99mTc-RGD2 starting from optic images in a murine model

    International Nuclear Information System (INIS)

    Cornejo A, L. G.

    2015-01-01

    This work has the purpose of evaluate the biokinetics and absorbed dose of radiation of hybrid formulation 99m Tc-BN / 99m Tc-RGD 2 in a murine model by optical imaging techniques using the multimodal preclinical in vivo image system Xtreme. The used method were the 99m Tc-BN, 99m Tc-RGD 2 and 99m Tc-BN/ 99m Tc-RGD 2 formulas, with specific recognition for GRPr and the integrin s α(v)β(3) and α(v)β(5) respectively, was injected in the vein tail of three nude mousses with induce breast cancer tumors (cell line T-47-D), by the preclinical multimodal imaging system Xtreme (Bruker), optical images in different times was acquired (5, 10, 20 min, 2 and 24 h), using Images Processing Toolbox of MATLAB these images was transform from RGB format to gray scales and sectioned in five independent images corresponding to heart, kidneys, bladder and tumor areas. The intensity of each images was computed in counts per pixel, then those intensities was corrected for background, attenuation and scattering, using different factors for each phenomena previously calculated. Finally the activity values quantified vs time was fitted into a biokinetic model to obtain the disintegrations number and cumulate activities in each organ. With these data the radiation absorbed dose were calculated using MIRD methodology. Results: The number of disintegration and absorbed dose calculated in MBq h/MBq and mGy/MBq, of injected mouse with the 99m Tc-BN/ 99m Tc-RGD 2 formulation, was: 0.035 ± 0.65 E-02, 0.25 x 10 -5 ± 0.46 E-07; 0.393 ± 0.51 E-1, 2.85 E-05 ± 3.7 E-06; 0.306 ± 0.21 E-01, 2.11 E-05 ± 1.45 E-06 and 0.151 ± 0.19 E-01, 1.09 E-05 ± 1.42 E-06 , in heart, kidneys, bladder and tumor, respectively. The number of disintegration obtained in kidneys is comparable to those reported for Trinidad B. 2014 Conclusions: Our results demonstrated that using optical images and a code for image analyses development in MATLAB, could achieve comparable quantitative results as the conventional

  11. Computer analysis of antigenic domains and RGD-like sequences (RGWG) in the E glycoprotein of flaviviruses: an approach to vaccine development.

    Science.gov (United States)

    Becker, Y

    1990-09-01

    Antigenic domains and RGD-like sequences in the E glycoprotein of the flaviviruses Japanese encephalitis virus, yellow fever virus, West Nile virus, dengue type 4 virus, and tick-borne encephalitis virus were analyzed by computer programs that provide information on the physical properties of the polypeptides. The use of computer programs for the development of vaccines based on the synthesis of antigenic peptides is discussed. Synthetic viral peptides are proposed to be used for topical application so as to interfere with the virus-cell interaction. Viral peptides with antigenic epitopes to protect against dengue virus infection without enhancing pathogenesis may also be developed on the basis of the computer analysis.

  12. Modelling conjugation with stochastic differential equations.

    Science.gov (United States)

    Philipsen, K R; Christiansen, L E; Hasman, H; Madsen, H

    2010-03-07

    Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared to the model without plate conjugation. The modelling approach described in this article can be applied generally when modelling dynamical systems. 2009 Elsevier Ltd. All rights reserved.

  13. The Tcp conjugation system of Clostridium perfringens.

    Science.gov (United States)

    Wisniewski, Jessica A; Rood, Julian I

    2017-05-01

    The Gram-positive pathogen Clostridium perfringens possesses a family of large conjugative plasmids that is typified by the tetracycline resistance plasmid pCW3. Since these plasmids may carry antibiotic resistance genes or genes encoding extracellular or sporulation-associated toxins, the conjugative transfer of these plasmids appears to be important for the epidemiology of C. perfringens-mediated diseases. Sequence analysis of members of this plasmid family identified a highly conserved 35kb region that encodes proteins with various functions, including plasmid replication and partitioning. The tcp conjugation locus also was identified in this region, initially based on low-level amino acid sequence identity to conjugation proteins from the integrative conjugative element Tn916. Genetic studies confirmed that the tcp locus is required for conjugative transfer and combined with biochemical and structural analyses have led to the development of a functional model of the Tcp conjugation apparatus. This review summarises our current understanding of the Tcp conjugation system, which is now one of the best-characterized conjugation systems in Gram-positive bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Chemistry of Oligonucleotibe-Gold Nanoparticle Conjugates

    National Research Council Canada - National Science Library

    Letsinger, Robert

    2003-01-01

    Conjugates prepared by immobilizing thiol-terminated oligonucleotides onto gold nanoparticles from stable colloidal solutions in aqueous media The oligo nucleotides can serve as linkers to organize...

  15. Modelling conjugation with stochastic differential equations

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Hasman, Henrik

    2010-01-01

    using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared......Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two...

  16. Cell Adhesion on RGD-Displaying Knottins with Varying Numbers of Tryptophan Amino Acids to Tune the Affinity for Assembly on Cucurbit[8]uril Surfaces.

    Science.gov (United States)

    Sankaran, Shrikrishnan; Cavatorta, Emanuela; Huskens, Jurriaan; Jonkheijm, Pascal

    2017-09-05

    Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV 2+ ). The binding affinity of the knottins with CB[8] and MV 2+ surfaces was evaluated using surface plasmon resonance spectroscopy. Specific binding occurred, and the affinity increased with the valency of tryptophans on the knottin. Additionally, increased multilayer formation was observed, attributed to homoternary complex formation between tryptophan residues of different knottins and CB[8]. Thus, we were able to control the surface coverage of the knottins by valency and concentration. Cell experiments with mouse myoblast (C2C12) cells on the self-assembled knottin surfaces showed specific integrin recognition by the RGD-displaying knottins. Moreover, cells were observed to elongate more on the supramolecular knottin surfaces with a higher valency, and in addition, more pronounced focal adhesion formation was observed on the higher-valency knottin surfaces. We attribute this effect to the enhanced coverage and the enhanced affinity of the knottins in their interaction with the CB[8] surface. Collectively, these results are promising for the development of biomaterials including knottins via CB[8] ternary complexes for tunable interactions with cells.

  17. Subgap Absorption in Conjugated Polymers

    Science.gov (United States)

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  18. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    DEFF Research Database (Denmark)

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  19. Parallel synthesis and screening of peptide conjugates.

    Science.gov (United States)

    Dirksen, Anouk; Madsen, Mark; Dello Iacono, Giuseppe; Matin, Marla J; Bacica, Michael; Stanković, Nebojša; Callans, Sherri; Bhat, Abhijit

    2014-06-18

    Peptide conjugates represent an emerging class of therapeutics. However, in contrast to that of small molecules and peptides, the discovery and optimization of peptide conjugates is low in throughput, resource intensive, time-consuming, and based on educated decisions rather than screening. A strategy for the parallel synthesis and screening of peptide conjugates is presented that (1) reduces variability in the conjugation steps; (2) provides a new method to rapidly and quantitatively measure conversion in crude conjugation mixtures; (3) introduces a purification step using an immobilized chemical scavenger that does not rely on protein-specific binding; and (4) is supported by robust analytical methods to characterize the large number of end products. Copper-free click chemistry is used as the chemoselective ligation method for conjugation and purification. The productivity in the generation and screening of peptide conjugates is significantly improved by applying this strategy as is demonstrated by the optimization of the anti-Angiopoietin-2 (Ang2) CovX-body, CVX-060, a peptide-antibody scaffold conjugate that has advanced in clinical trials for oncology indications.

  20. Catalytic enantioselective conjugate addition with Grignard reagents

    NARCIS (Netherlands)

    Lopez, Fernando; Minnaard, Adriaan J.; Feringa, Ben L.

    In this Account, recent advances in catalytic asymmetric conjugate addition of Grignard reagents are discussed. Synthetic methodology to perform highly enantioselective Cu-catalyzed conjugate addition of Grignard reagents to cyclic enones with ee's up to 96% was reported in 2004 from our

  1. Tales of conjugation and sex pheromones

    Science.gov (United States)

    2011-01-01

    This review covers highlights of the author's experience becoming and working as a plasmid biologist. The account chronicles a progression from studies of ColE1 DNA in Escherichia coli to Gram-positive bacteria with an emphasis on conjugation in enterococci. It deals with gene amplification, conjugative transposons and sex pheromones in the context of bacterial antibiotic resistance. PMID:22016844

  2. Bio-Conjugates for Nanoscale Applications

    DEFF Research Database (Denmark)

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  3. Preconditioning the modified conjugate gradient method ...

    African Journals Online (AJOL)

    In this paper, the convergence analysis of the conventional conjugate Gradient method was reviewed. And the convergence analysis of the modified conjugate Gradient method was analysed with our extension on preconditioning the algorithm. Convergence of the algorithm is a function of the condition number of M-1A.

  4. Singularities and Conjugate Points in FLRW Spacetimes

    NARCIS (Netherlands)

    Lam, Huibert het; Prokopec, Tom

    2017-01-01

    Conjugate points play an important role in the proofs of the singularity theorems of Hawking and Penrose. We examine the relation between singularities and conjugate points in FLRW spacetimes with a singularity. In particular we prove a theorem that when a non-comoving, non-spacelike geodesic in a

  5. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    NARCIS (Netherlands)

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  6. The Conjugate Acid-Base Chart.

    Science.gov (United States)

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  7. Approximate error conjugation gradient minimization methods

    Science.gov (United States)

    Kallman, Jeffrey S

    2013-05-21

    In one embodiment, a method includes selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, calculating an approximate error using the subset of rays, and calculating a minimum in a conjugate gradient direction based on the approximate error. In another embodiment, a system includes a processor for executing logic, logic for selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, logic for calculating an approximate error using the subset of rays, and logic for calculating a minimum in a conjugate gradient direction based on the approximate error. In other embodiments, computer program products, methods, and systems are described capable of using approximate error in constrained conjugate gradient minimization problems.

  8. Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes

    Directory of Open Access Journals (Sweden)

    Carbone Maria

    2006-09-01

    Full Text Available Abstract Background Mammalian sperm-oocyte interaction at fertilization involves several combined interactions between integrins on the oocyte and integrin ligands (disintegrins on the sperm. Recent research has indicated the ability of peptides containing the RGD sequence that characterized several sperm disintegrins, to induce intracellular Ca2+ transients and to initiate parthenogenetic development in amphibian and bovine oocytes. In the present study, we investigate the hypothesis that an integrin-associated signalling may participate in oocyte activation signalling by determining the ability of a cyclic RGD-containing peptide to stimulate the activation of protein kinase C (PKC and the exocytosis of cortical granules in mouse oocytes. Methods An In-Vitro-Fertilization assay (IVF was carried in order to test the condition under which a peptide containing the RGD sequence, cyclo(Arg-Gly-Asp-D-Phe-Val, was able to inhibit sperm fusion with zona-free mouse oocytes at metaphase II stage. PKC activity was determined by means of an assay based on the ability of cell lysates to phosphorylate MARKS peptide, a specific PKC substrate. Loss of cortical granules was evaluated by measuring density in the oocyte cortex of cortical granules stained with LCA-biotin/Texas red-streptavidin. In all the experiments, effects of a control peptide containing a non RGD sequence, cyclo(Arg-Ala-Asp-D-Phe-Val, were evaluated. Results The IVF assay revealed that the fusion rate declined significantly when insemination was carried out in the presence of cyclic RGD peptide at concentrations > or = 250 microM (P Conclusion The presents results provide evidence that a cyclic RGD peptide highly effective in inhibiting sperm-oocyte interaction stimulates in mouse oocytes the activation of PKC and the exocytosis of cortical granules. These data support the view that RGD-binding receptors may function as signalling receptors giving rise integrated signalling not sufficient for

  9. TAT peptide and its conjugates: proteolytic stability.

    Science.gov (United States)

    Grunwald, Jacob; Rejtar, Tomas; Sawant, Rupa; Wang, Zhouxi; Torchilin, Vladimir P

    2009-08-19

    The proteolytic cleavage of TATp, TATp-PEG(1000)-PE conjugate (TATp-conjugate), and TATp as TATp-conjugate in mixed micelles made of TATp-conjugate and PEG(5000)-PE (2.5% mol of TATp-conjugate, TATp-Mic) were studied by HPLC with fluorescent detection using fluorenylmethyl chloroformate (FMOC) labeling and by MALDI-TOF MS analysis. The cleavage kinetics were analyzed in human blood plasma and in trypsin-containing phosphate buffered saline (PBS), pH 7.4, to simulate the proteolytic activity of human plasma. The trypsinolysis of free TATp, TATp-conjugate, and TATp-Mic revealed that the main initial fragmentation is an endocleavage at the carboxyl terminus resulting in an Arg-Arg (RR) dimer. The trypsinolysis followed pseudo-first-order kinetics. The cleavage of the free TATp was relatively fast with a half-life of a few minutes (t(1/2) ∼ 3.5 min). The TATp-conjugate showed more stability with about a 3-fold increase in half-life (t(1/2) ∼ 10 min). TATp in TATp-Mic was highly protected against proteolysis with an over 100-fold increase in half-life (t(1/2) ∼ 430 min). The shielding of TATp by PEG moieties in the proposed TATp-Mic is of great importance for its potential use as a cell-penetrating moiety for multifunctional "smart" drug delivery systems with detachable PEG.

  10. Optimization of the production process of hybrid and multivalent formulation Bombesin/RGD for the opportune detection of breast cancer; Optimizacion del proceso de fabricacion de la formulacion hibrida y multivalente Bombesina/RGD para la deteccion oportuna de cancer de mama

    Energy Technology Data Exchange (ETDEWEB)

    Robles M, M.

    2013-07-01

    The radiopharmaceuticals of third generation are used in nuclear medicine to obtain images of specific molecular targets, and they are unique in their capacity to detect in vivo specific biochemical sites as receptors that are over-expressed in diverse illness. In cancer cells several types of receptors are over-expressed, as the integrin s α(v)β(3) and α(v)β(5) that specifically recognize the sequence RGD (Arginine-Glycin-Ac. Aspartic) and gastrin-releasing peptide that recognizes specifically to the peptide Lys{sup 3}-Bombesin. The integrin s α(v)β(3) and α(v)β(5) are involved in the tumor angio genesis processes and the gastrin-releasing peptide is over-expressed in breast and prostate cancer. The molecular recognition of the specific receptors is the basis to be utilized as targets of the radiopharmaceuticals {sup 99m}Tc-HYNIC-Bombesin and {sup 99m}Tc-HYNIC-RGD. In this work was developed a lyophilized pharmaceutical formulation effective, stable and safe for the simultaneous obtaining of the radiopharmaceuticals {sup 99m}Tc-HYNIC-Bombesin ({sup 99m}Tc-EDDA/HYNIC-Lys{sup 3}-Bombesin) and {sup 99m}Tc-HYNIC-RGD ({sup 99m}Tc EDDA/HYNIC-E-[c(RGDfK)]{sub 2}). Later on the production process of the product HYNIC-Bombesin/RGD-Sn was optimized using a factorial design and the formulation was transferred to the production plant of radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ). The optimized formulation is described in the following chart: HYNIC-[Lys{sup 3}]-Bombesin - 12.5 μg; HYNIC-E-c[RGDfK]{sub 2} - 12.5 μg; Stannous chloride (SnCl{sub 2}) - 20 μg; Ethylenediamine diacetic acid (EDDA) - 10 mg; N-tris(hydroxymethyl)methyl glycin (Tricine) - 20 mg; Mannitol - 50 mg. The production process was validated and were carried out the stability studies under refrigeration conditions. (Author)

  11. Biokinetics and dosimetry of a hybrid formulation of {sup 9{sup m}}Tc-BN and {sup 99m}Tc-RGD{sub 2} starting from optic images in a murine model; Biocinetica y dosimetria de una formulacion hibrida de {sup 99m}Tc-BN y {sup 99m}Tc-RGD{sub 2} a partir de imagenes opticas en un modelo murino

    Energy Technology Data Exchange (ETDEWEB)

    Cornejo A, L. G.

    2015-07-01

    This work has the purpose of evaluate the biokinetics and absorbed dose of radiation of hybrid formulation {sup 99m}Tc-BN /{sup 99m}Tc-RGD{sub 2} in a murine model by optical imaging techniques using the multimodal preclinical in vivo image system Xtreme. The used method were the {sup 99m}Tc-BN, {sup 99m}Tc-RGD{sub 2} and {sup 99m}Tc-BN/{sup 99m}Tc-RGD{sub 2} formulas, with specific recognition for GRPr and the integrin s α(v)β(3) and α(v)β(5) respectively, was injected in the vein tail of three nude mousses with induce breast cancer tumors (cell line T-47-D), by the preclinical multimodal imaging system Xtreme (Bruker), optical images in different times was acquired (5, 10, 20 min, 2 and 24 h), using Images Processing Toolbox of MATLAB these images was transform from RGB format to gray scales and sectioned in five independent images corresponding to heart, kidneys, bladder and tumor areas. The intensity of each images was computed in counts per pixel, then those intensities was corrected for background, attenuation and scattering, using different factors for each phenomena previously calculated. Finally the activity values quantified vs time was fitted into a biokinetic model to obtain the disintegrations number and cumulate activities in each organ. With these data the radiation absorbed dose were calculated using MIRD methodology. Results: The number of disintegration and absorbed dose calculated in MBq h/MBq and mGy/MBq, of injected mouse with the {sup 99m}Tc-BN/{sup 99m}Tc-RGD{sub 2} formulation, was: 0.035 ± 0.65 E-02, 0.25 x 10{sub -5} ± 0.46 E-07; 0.393 ± 0.51 E-1, 2.85 E-05 ± 3.7 E-06; 0.306 ± 0.21 E-01, 2.11 E-05 ± 1.45 E-06 and 0.151 ± 0.19 E-01, 1.09 E-05 ± 1.42 E-06 , in heart, kidneys, bladder and tumor, respectively. The number of disintegration obtained in kidneys is comparable to those reported for Trinidad B. 2014 Conclusions: Our results demonstrated that using optical images and a code for image analyses development in MATLAB, could

  12. Comparison of radiolabeling efficiency of peptides containing the RGD domain using the Tc-99M and I-131 radioisotopes

    Energy Technology Data Exchange (ETDEWEB)

    Sobral, Danielle V.; Cabral, Francisco Romero; Malavolta, Luciana [Santa Casa de São Paulo, SP (Brazil). Faculdade de Ciências Médicas; Durante, Ana C. Ranucci; Miranda, Ana C. Camargo; Barbosa, Marycel R. F.Figols de [Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Radiolabeled peptides have become very important in nuclear medicine and oncology in recent years mainly because they represent the molecular basis for in vivo imaging and radiopharmaceutical therapy with high specificity and affinity for over expressed receptors in tumors (Thno 2(5):481-501, 2012 / Drug Discov. Today. 7:1224-1232, 2012). In this context, peptides containing the RGD domain which possess high affinity for the αvβ3 integrin receptor have become an important tool in a wide variety tumor, including glioblastoma (Exp. Opin. Drug Deliv. 8:1041- 1056, 2011). Objective: The goal of this work was to compare the radiolabeling efficiency of the GRGDYV and GRGDHV peptides when radiolabeled with the {sup 131}I and {sup 99m}Tc radioisotopes, respectively, as well as, to evaluate the features of synthesized complexes. Methods: The GRGDYV and GRGDHV fragments were manually synthesized by peptide synthesis in solid phase accordingly to the Fmoc protocol and purified by preparative HPLC. The GRGDYV and GRGDHV peptides were radiolabeled with the I-131 and Tc-99m radioisotopes respectively, through of the direct method of radiolabeling. The radioiodination was evaluated and optimized using the methodology of Chloramine-T and for the peptide containing the histidine aminoacid the tricarbonyl method was used. Radiochemical yield analyses of [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV peptides were performed by thin layer chromatography on silica gel TLC-SG (Al) in ACN 95%. The radiolabeled peptides were purified by using solid phase extraction (Sep-Pak C18 filter). The stability studies were realized at 2, 24, 48 and 72 hours in room temperature and refrigerate (4 deg C) for [{sup 131}I]-GRGDYV and up to 6 hours for the fragment [{sup 99m}Tc]-GRGDHV. Partition coefficient was determinate for both radiopeptides. Results: The peptides [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV were efficiently synthesized, radiolabeled and showed

  13. Conjugated Polymers and Oligomers: Structural and Soft Matter Aspects

    DEFF Research Database (Denmark)

    conjugated polymer backbone, water soluble conjugated polyelectrolytes and surfactants, conjugated molecules and biomolecules and DNA and the advanced use of synchrotron radiation and electron microscopy to find out structural details in conjugated molecule films and devices as well as under ambient...

  14. Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri-Implantitis.

    Science.gov (United States)

    Diniz, Ivana M A; Chen, Chider; Ansari, Sahar; Zadeh, Homayoun H; Moshaverinia, Maryam; Chee, Daniel; Marques, Márcia M; Shi, Songtao; Moshaverinia, Alireza

    2016-02-01

    Peri-implantitis is one of the most common inflammatory complications in dental implantology. Similar to periodontitis, in peri-implantitis, destructive inflammatory changes take place in the tissues surrounding a dental implant. Bacterial flora at the failing implant sites resemble the pathogens in periodontal disease and consist of Gram-negative anaerobic bacteria including Aggregatibacter actinomycetemcomitans (Aa). Here we demonstrate the effectiveness of a silver lactate (SL)-containing RGD-coupled alginate hydrogel scaffold as a promising stem cell delivery vehicle with antimicrobial properties. Gingival mesenchymal stem cells (GMSCs) or human bone marrow mesenchymal stem cells (hBMMSCs) were encapsulated in SL-loaded alginate hydrogel microspheres. Stem cell viability, proliferation, and osteo-differentiation capacity were analyzed. Our results showed that SL exhibited antimicrobial properties against Aa in a dose-dependent manner, with 0.50 mg/ml showing the greatest antimicrobial properties while still maintaining cell viability. At this concentration, SL-containing alginate hydrogel was able to inhibit Aa growth on the surface of Ti discs and significantly reduce the bacterial load in Aa suspensions. Silver ions were effectively released from the SL-loaded alginate microspheres for up to 2 weeks. Osteogenic differentiation of GMSCs and hBMMSCs encapsulated in the SL-loaded alginate microspheres were confirmed by the intense mineral matrix deposition and high expression of osteogenesis-related genes. Taken together, our findings confirm that GMSCs encapsulated in RGD-modified alginate hydrogel containing SL show promise for bone tissue engineering with antimicrobial properties against Aa bacteria in vitro. © 2015 by the American College of Prosthodontists.

  15. Oligonucleotides conjugated to short lysine chains.

    Science.gov (United States)

    Winkler, Johannes; Urban, Ernst; Noe, Christian R

    2005-01-01

    A new method for synthesizing oligonucleotide peptide conjugates by an in-line approach is presented. A phosphorothioate oligonucleotide with the sequence of bcl-2 targeted Oblimersen by employing a modified 2'-amino-2'-desoxy-uridine nucleotide bearing a succinyl linker at the 2' position was prepared. The carboxyl group was protected for solid-phase synthesis as the benzyl ester. Ester cleavage was afforded by a phase transfer reaction using palladium nanoparticles as catalyst and cyclohexadiene as hydrogen donor. Short tails of up to three lysyl residues were conjugated to the oligonucleotide by an inverse stepwise peptide synthesis. The conjugates were characterized by HPLC, mass spectrometry, and circular dichroism. Influence of lysyl tails on CD spectra were minimal. Melting profiles revealed only minimal destabilizing effects on duplexes by conjugation of peptides.

  16. Stochastic differential equations used to model conjugation

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo

    be split into measurement noise and system noise. The system noise is used to compensate for those biological processes not explicitly described by the model. Many authors model conjugation by a simple mass action model first proposed by Levin et al. (1979). Also Michaelis-Menten dependence...... by an experiment conducted with E. faecium. In addition, we suggest that a 3rd order time-delay must be included in the model to account for the delay before a newly conjugated plasmid is expressed. A ML estimate of the parameters based on experimental data is found using the software CTSM. The conjugation rate......Stochastic differential equations (SDEs) are used to model horizontal transfer of antibiotic resis- tance by conjugation. The model describes the concentration of donor, recipient, transconjugants and substrate. The strength of the SDE model over the traditional ODE models is that the noise can...

  17. Deciphering conjugative plasmid permissiveness in wastewater microbiomes

    DEFF Research Database (Denmark)

    Jacquiod, Samuel Jehan Auguste; Brejnrod, Asker Daniel; Milani, Stefan Morberg

    2017-01-01

    Wastewater treatment plants (WWTPs) are designed to robustly treat polluted water. They are characterized by ceaseless flows of organic, chemical and microbial matter, followed by treatment steps before environmental release. WWTPs are hotspots of horizontal gene transfer between bacteria via...... conjugative plasmids, leading to dissemination of potentially hazardous genetic material such as antimicrobial resistance genes (AMRGs). While current focus is on the threat of AMRGs spreading and their environmental maintenance, conjugative plasmid transfer dynamics within and between bacterial communities...... still remains largely uncharted. Furthermore, current in vitro methods used to assess conjugation in complex microbiomes do not include in situ behaviours of recipient cells, resulting in partial understanding of transfers. We investigated the in vitro conjugation capacities of WWTP microbiomes from...

  18. Design and Application of Antimicrobial Peptide Conjugates

    Directory of Open Access Journals (Sweden)

    Andre Reinhardt

    2016-05-01

    Full Text Available Antimicrobial peptides (AMPs are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

  19. Energetic Tuning in Spirocyclic Conjugated Polymers

    OpenAIRE

    Hugo Bronstein; Frank D. King

    2016-01-01

    Precise control of the energy levels in a conjugated polymer is the key to allowing their exploitation in optoelectronic devices. The introduction of spirocycles into conjugated polymers has traditionally been used to enhance their solid state microstructure. Here we present a highly novel method of energetic tuning through the use of electronically active spirocyclic systems. By modifying the size and oxidation state of a heteroatom in an orthogonal spirocycle we demonstrate energetic fine t...

  20. Two-zone double phase conjugate mirror

    Science.gov (United States)

    Belić, M. R.; Vujić, D.; Sandfuchs, O.; Kaiser, F.

    2001-10-01

    An analysis of photorefractive (PR) oscillators consisting of two facing four-wave mixing regions is carried out. The threshold and operation conditions of different phase conjugate mirrors are discussed with the help of the grating action method. In particular, the threshold and the operation of the two-zone double phase conjugate mirror (DPCM) is compared with other related PR oscillators, the interconnected ring, and different connected DPCM.

  1. Rapid modification of retroviruses using lipid conjugates

    International Nuclear Information System (INIS)

    Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L

    2009-01-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  2. Syntheses of conjugated polymers for photonics

    Czech Academy of Sciences Publication Activity Database

    Výprachtický, Drahomír; Cimrová, Věra; Kmínek, Ivan; Pavlačková, Petra

    2010-01-01

    Roč. 295, č. 1 (2010), s. 94-99 ISSN 1022-1360. [Prague Meetings on Macromolecules /73./ New Frontiers in Macromolecular Science: From Macromolecular Concepts of Living Matter to Polymers for Better Quality of Life. Prague, 05.07.2009-09.07.2009] R&D Projects: GA MŠk(CZ) 1M06031 Institutional research plan: CEZ:AV0Z40500505 Keywords : cis and trans isomers * conjugated polymer * conjugated polyelectrolyte Subject RIV: BM - Solid Matter Physics ; Magnetism

  3. Conjugation in Gram-Positive Bacteria.

    Science.gov (United States)

    Goessweiner-Mohr, Nikolaus; Arends, Karsten; Keller, Walter; Grohmann, Elisabeth

    2014-08-01

    Conjugative transfer is the most important means of spreading antibiotic resistance and virulence factors among bacteria. The key vehicles of this horizontal gene transfer are a group of mobile genetic elements, termed conjugative plasmids. Conjugative plasmids contain as minimum instrumentation an origin of transfer (oriT), DNA-processing factors (a relaxase and accessory proteins), as well as proteins that constitute the trans-envelope transport channel, the so-called mating pair formation (Mpf) proteins. All these protein factors are encoded by one or more transfer (tra) operons that together form the DNA transport machinery, the Gram-positive type IV secretion system. However, multicellular Gram-positive bacteria belonging to the streptomycetes appear to have evolved another mechanism for conjugative plasmid spread reminiscent of the machinery involved in bacterial cell division and sporulation, which transports double-stranded DNA from donor to recipient cells. Here, we focus on the protein key players involved in the plasmid spread through the two different modes and present a new secondary structure homology-based classification system for type IV secretion protein families. Moreover, we discuss the relevance of conjugative plasmid transfer in the environment and summarize novel techniques to visualize and quantify conjugative transfer in situ.

  4. Cross-conjugation and quantum interference: a general correlation?

    DEFF Research Database (Denmark)

    Valkenier, Hennie; Guedon, Constant M.; Markussen, Troels

    2014-01-01

    -conjugation patterns, but identical lengths, i.e. an anthracene (linear conjugation), an anthraquinone (cross-conjugation), and a dihydroanthracene (broken conjugation) derivative. To benchmark reliable trends, conductance experiments on these series have been performed by various techniques. Here, we compare data...... characterized by beta = 0.37 +/- 0.03 angstrom(-1) (CP-AFM). Remarkably, for the second series, we do not only find that the linearly conjugated anthracene-containing wire is the most conductive, but also that the cross-conjugated anthraquinone-containing wire is less conductive than the broken...

  5. Water-Solubilizing Hydrophobic ZnAgInSe/ZnS QDs with Tumor-Targeted cRGD-Sulfobetaine-PIMA-Histamine Ligands via a Self-Assembly Strategy for Bioimaging.

    Science.gov (United States)

    Deng, Tao; Peng, Yanan; Zhang, Rong; Wang, Jie; Zhang, Jie; Gu, Yueqing; Huang, Dechun; Deng, Dawei

    2017-04-05

    Exploring the organic-to-aqueous phase transfer of quantum dots (QDs) is significant for achieving their versatile applications in biomedical fields. In this thematic issue, surface modification, size control, and biocompatibility of QDs and QDs-based nanocomposites are core problems. Herein, the new highly fluorescent tumor-targeted QDs-clusters consisting of ZnAgInSe/ZnS (ZAISe/ZnS) QDs and sulfobetaine-PIMA-histamine (SPH) polymer with the α ν β 3 integrin receptor cyclic RGD (c-RGD) were developed via ligand exchange and an accompanying self-assembly process. It was found that the structure of RGD-SPH QDs-clusters was propitious to reduce the capture of reticulo-endothelial system (RES) in virtue of external stealth ligands, and benefit to selectively accumulate at the tumor site after intravenous injection via active tumor targeting cooperated with the enhanced permeability and retention (EPR) effect. In the meantime, those clusters also recognized and enriched the cell surface when cocultured with the α ν β 3 integrin receptor overexpressed malignant cells (U87MG tumor). On the basis of the results, fabricating mutil-functional nanocomposites integrated with the long-term circulation and dual-targeting effects should be an interesting strategy for imaging cancer in vitro and in vivo.

  6. Phase conjugate Michelson interferometer for optical logic

    Science.gov (United States)

    Khoury, Jed

    2017-05-01

    The interference theory is developed for of the phase conjugate Michelson interferometer in which its ordinary mirrors are replaced by a single externally pumped phase conjugate mirror. According to the theory, it was found that for an interferometer with two equal arms, the path length difference depends solely on the initial alignment of the two input beams, and the vertical alignment readout. Small vertical misalignments in the readout beam by mrad causes a huge change in the phase difference in the phase between the two interferometer arms beam. The phase difference is proportional to the interferometer arm lengths. The overlap between the phase conjugate beams is not affected by the interferometer beam alignment. The interferometer is proposed for nondestructive testing and the design all optical logic and associated fuzzy logic for ultrafast optical pattern recognition.

  7. Tight-binding treatment of conjugated polymers

    DEFF Research Database (Denmark)

    Lynge, Thomas Bastholm

    This PhD thesis concerns conjugated polymers which constitute a constantly growing research area. Today, among other things, conjugated polymers play a role in plastic based solar cells, photodetectors and light emitting diodes, and even today such plastic-based components constitute an alternative...... of tomorrow. This thesis specifically treats the three conjugated polymers trans-polyacetylene (tPA), poly(para-phenylene) (PPP) and poly(para-phe\\-nylene vinylene) (PPV). The present results, which are derived within the tight-binding model, are divided into two parts. In one part, analytic results...... are derived for the optical properties of the polymers expressed in terms of the optical susceptibility both in the presence and in the absence of a static electric field. In the other part, the cumputationally efficient Density Functional-based Tight-Binding (DFTB) model is applied to the description...

  8. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

  9. Nonlinear conjugate gradient methods in micromagnetics

    Directory of Open Access Journals (Sweden)

    J. Fischbacher

    2017-04-01

    Full Text Available Conjugate gradient methods for energy minimization in micromagnetics are compared. The comparison of analytic results with numerical simulation shows that standard conjugate gradient method may fail to produce correct results. A method that restricts the step length in the line search is introduced, in order to avoid this problem. When the step length in the line search is controlled, conjugate gradient techniques are a fast and reliable way to compute the hysteresis properties of permanent magnets. The method is applied to investigate demagnetizing effects in NdFe12 based permanent magnets. The reduction of the coercive field by demagnetizing effects is μ0ΔH = 1.4 T at 450 K.

  10. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Science.gov (United States)

    Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

    2011-01-01

    Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444

  11. Serogroup A meningococcal conjugate vaccines in Africa.

    Science.gov (United States)

    Kristiansen, Paul A; Jørgensen, Hannah J; Caugant, Dominique A

    2015-01-01

    Serogroup A meningococcal epidemics have been a recurrent public health problem, especially in resource-poor countries of Africa. Recently, the administration in mass vaccination campaigns of a single dose of the monovalent meningococcal conjugate vaccine, MenAfriVac, to the 1-29 year-old population of sub-Saharan Africa has prevented epidemics of meningitis caused by serogroup A Neisseria meningitidis. This strategy has also been shown to provide herd protection of the non-vaccinated population. Development of meningococcal conjugate vaccines covering other serogroups and enhanced use of the pneumococcal and Haemophilus influenzae type b conjugate vaccines must be pursued to fully control bacterial meningitis in sub-Saharan Africa.

  12. Conjugate gradient algorithms using multiple recursions

    Energy Technology Data Exchange (ETDEWEB)

    Barth, T.; Manteuffel, T.

    1996-12-31

    Much is already known about when a conjugate gradient method can be implemented with short recursions for the direction vectors. The work done in 1984 by Faber and Manteuffel gave necessary and sufficient conditions on the iteration matrix A, in order for a conjugate gradient method to be implemented with a single recursion of a certain form. However, this form does not take into account all possible recursions. This became evident when Jagels and Reichel used an algorithm of Gragg for unitary matrices to demonstrate that the class of matrices for which a practical conjugate gradient algorithm exists can be extended to include unitary and shifted unitary matrices. The implementation uses short double recursions for the direction vectors. This motivates the study of multiple recursion algorithms.

  13. CO-releasing molecule (CORM) conjugate systems.

    Science.gov (United States)

    Kautz, Anna Christin; Kunz, Peter C; Janiak, Christoph

    2016-11-15

    The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks. We discuss in this review the known CORM carrier conjugates, in short CORM conjugates, with covalently-bound or incorporated CORMs for medicinal and therapeutic applications. Most conjugates are nontoxic, show increasing half-lives of CO release, and make use of the EPR-effect, but still show problems because of a continuous background of CO release and the absence of an on/off-switch for the CO release.

  14. Conjugated Polymers as Actuators: Modes of Actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2004-01-01

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  15. Functionalized conjugated polyelectrolytes design and biomedical applications

    CERN Document Server

    Wang, Shu

    2014-01-01

    Functionalized Conjugated Polyelectrolytes presents a comprehensive review of these polyelectrolytes and their biomedical applications. Basic aspects like molecular design and optoelectronic properties are covered in the first chapter. Emphasis is placed on the various applications including sensing (chemical and biological), disease diagnosis, cell imaging, drug/gene delivery and disease treatment. This book explores a multi-disciplinary topic of interest to researchers working in the fields of chemistry, materials, biology and medicine. It also offers an integrated perspective on both basic research and application issues. Functionalized conjugated polyelectrolyte materials, which have already drawn considerable interest, will become a major new direction for biomedicine development.

  16. Conjugated polymers as actuators: modes of actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  17. De-conjugation behavior of conjugated estrogens in the raw sewage, activated sludge and river water.

    Science.gov (United States)

    Kumar, Vimal; Johnson, Andrew C; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki

    2012-08-15

    The fate and behavior of estrone-3-sulfate (E1-3S), estradiol-3-sulfate (E2-3S), estrone-3-glucuronide (E1-3G) and estradiol-3-glucuronide (E2-3G) were studied in raw sewage, activated sludge and river water using microcosms. The glucuronide conjugates had a half-life of 0.4h in raw sewage, yielding 40-60% of their free estrogens. Field observations at three activated sludge processes suggested complete transformation of the glucuronide conjugates in the sewer. In river water glucuronide conjugates half-lives extended to over 2d yielding 60-100% of their free parent estrogens. Transformation of the sulfate conjugates in raw sewage and river water was slow with little formation of the parent estrogens. Sulfate conjugates could readily be detected in sewage influent in the field studies. In activated sludge the sulfate conjugates had half-lives of 0.2h with the transient formation of 10-55% of the free parent estrogens. Field studies indicated transformation of sulfate conjugates across the sewage treatment, although a proportion escaped into the effluent. These results broadly support the view that glucuronide conjugates will be entirely transformed within the sewer largely to their parent estrogens. The sulfate conjugates may persist in raw sewage and river water but are transformable in activated sludge and, in the case of E2-3S, reform a high proportion of the parent estrogen. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Initial in vitro and in vivo assessment of Au@DTDTPA-RGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging

    International Nuclear Information System (INIS)

    Tsoukalas, Charalmpos; Laurent, Gautier; Jiménez Sánchez, Gloria; Tsotakos, Theodoros; Bazzi, Rana; Stellas, Dimitris; Anagnostopoulos, Constantinos; Moulopoulos, Lia; Koutoulidis, Vasilis; Paravatou-Petsotas, Maria; Xanthopoulos, Stavros; Roux, Stephane; Bouziotis, Penelope

    2015-01-01

    Gadolinium chelate coated gold nanoparticles (Au@DTDTPA) can be applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. In this work, our aim was to radiolabel and evaluate this gold nanoparticle with Ga-68, in order to produce a dual modality PET/MRI imaging probe. For a typical preparation of 68Ga-labeled nanoparticles, the Au@DTDTPA nanoparticles (Au@DTDTPA/Au@DTDTPA-RGD) were mixed with ammonium acetate buffer, pH 5 and 40 MBq of 68Ga eluate. The mixture was then incubated for 45 min at 65 ÅãC. Radiochemical purity was determined by ITLC. In vitro stability of both radiolabeled species was assessed in saline and serum. In vitro cell binding experiments were performed on integrin ανβ3 receptor-positive U87MG cancer cells. Non-specific Au@DTDTPA was used for comparison. Ex vivo biodistribution studies and in vivo PET and MRI imaging studies in U87MG tumor-bearing SCID mice followed. The Au@DTDTPA nanoparticles were labeled with Gallium-68 at high radiochemical yield (>95%) and were stable at RT, and in the presence of serum, for up to 3 h. The cell binding assay on U87MG glioma cells proved that 68Ga-cRGD-Au@DTDTPA had specific recognition for these cells. Biodistribution studies in U87MG tumor-bearing SCID mice showed that the tumor to muscle ratio increased from 1 to 2 h p.i. (3,71 ± 0.22 and 4,69 ± 0.09 respectively), showing a clear differentiation between the affected and the non-affected tissue. The acquired PET and MRI images were in accordance to the ex vivo biodistribution results. The preliminary results of this study warrant the need for further development of Au@DTDTPA nanoparticles radiolabeled with Ga-68, as possible dual-modality PET/MRI imaging agents.

  19. Conjugation fidelity of double phase-conjugate mirrors in photorefractive materials with two-center transport.

    Science.gov (United States)

    Geri, I; Ozkul, C

    1996-11-01

    The temporal evolution of double phase-conjugate mirrors (DPCM's) in photorefractive materials such as BaTiO(3):Co:Fe is studied by use of the plane-wave expansion method. The buildup time of DPCM and its conjugation fidelity are compared with those of photorefractive materials with a single-center transport. Numerical simulations show that one can decrease the threshold value of the coupling strength required for the DPCM operation with a high conjugation fidelity by doping the BaTiO(3) crystals weakly with Co in comparison with undoped crystals.

  20. Efficient Xerographic Photoreceptors from Conjugated Polymers and Polymer Blends

    National Research Council Canada - National Science Library

    Zhang, Xuejun, Ph.D

    1998-01-01

    Bilayer xerographic photoreceptors in which pi-conjugated polymers and binary conjugated polymer blends are used as the charge generation layer have been fabricated, evaluated, and shown to be highly efficient...

  1. Functional analysis of the conjugation system from Clostridium perfringens

    OpenAIRE

    Wisniewski, Jessica Ann

    2017-01-01

    In Clostridium perfringens, toxins that cause histotoxic and gastrointestinal diseases have been identified on a family of large conjugative plasmids. The tcp transfer locus was initially identified on the prototype conjugative plasmid, pCW3. This locus has been shown to mediate conjugative plasmid transfer and studies on several of the Tcp proteins have identified their role in plasmid transfer. In general less is known about the mechanism of conjugative transfer in Gram positive bacteria, n...

  2. Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from {sup 68}Ga-RGD PET/CT and {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai-Jeon [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Ewha Womans University School of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Chun, In Kook [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kangwon National University Hospital, Department of Nuclear Medicine, Chuncheon, Kangwon-Do (Korea, Republic of); Cho, Nariya [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Im, Seock-Ah [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Jeong, Sunjoo [Dankook University, Department of Molecular Biology, Yongin (Korea, Republic of); Lee, Song [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Jung, Kyeong Cheon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Lee, Yun-Sang [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul (Korea, Republic of); Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2014-08-15

    Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes. In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6 ± 7.5 years old). {sup 68}Ga-Labeled arginine-glycine-aspartic acid (RGD) and {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}) from RGD PET/CT and SUV{sub max} and SUV{sub avg} from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered. Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88 ± 8.73 vs 10.48 ± 6.01, p = 0.02 for SUV{sub max}; 9.40 ± 5.19 vs 5.92 ± 4.09, p = 0.02 for SUV{sub avg}) and the PR-negative group (8.37 ± 4.94 vs 4.79 ± 3.93, p = 0.03 for SUV{sub avg}). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42 ± 0.59 vs 2.90 ± 0.75, p = 0.04 for SUV{sub max}; 1.60 ± 0.38 vs 1.95 ± 0.53, p = 0.04 for SUV{sub avg}) and showed a significant positive correlation with the HER2/CEP17 ratio (r = 0.38, p = 0.03 for SUV{sub max} and r = 0.46, p < 0.01 for SUV{sub avg}). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER

  3. Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and drug molecules for image-guided drug delivery and photodynamic therapy.

    Science.gov (United States)

    Yuan, Youyong; Liu, Bin

    2014-09-10

    A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer and drug carrier for combined photodynamic and chemotherapy. The amphiphilic brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous media with hydrophobic conjugated polyelectrolyte backbone as the core and hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm, with the absorption and emission maxima at 502 and 598 nm, respectively, making them suitable for bioimaging applications. Moreover, the CPE itself can serve as a photosensitizer, which makes the NPs not only a carrier for drug but also a photosensitizing unit for photodynamic therapy, resulting in the combination of chemo- and photodynamic therapy for cancer. The half-maximal inhibitory concentration (IC50) value for the combination therapy to U87-MG cells is 12.7 μg mL(-1), which is much lower than that for the solely photodynamic therapy (25.5 μg mL(-1)) or chemotherapy (132.8 μg mL(-1)). To improve the tumor specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD) tripeptide as the receptor to integrin αvβ3 overexpressed cancer cells was further incorporated to the surface of the NPs. The delivery system based on PEGylated CPE is easy to fabricate, which integrates the merits of targeted cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy, making it promising for cancer treatment.

  4. Women experiencing the intergenerationality of conjugal violence

    Directory of Open Access Journals (Sweden)

    Gilvânia Patrícia do Nascimento Paixão

    2015-10-01

    Full Text Available Objective: to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence.Method: qualitative study. Interviews were held with 19 women, who were experiencing conjugal violence, and who were resident in a community in Salvador, Bahia, Brazil. The project was approved by the Research Ethics Committee (N. 42/2011.Results: the data was organized using the Discourse of the Collective Subject, identifying the summary central ideas: they witnessed violence between their parents; they suffered repercussions from the violence between their parents: they were angry about the mother's submission to her partner; and they reproduced the conjugal violence. The discourse showed that the women witnessed, in childhood and adolescence, violence between their parents, and were injured both physically and psychologically. As a result of the mother's submission, feelings of anger arose in the children. However, in the adult phase of their own lives, they noticed that their conjugal life resembled that of their parents, reproducing the violence.Conclusion: investment is necessary in strategies designed to break inter-generational violence, and the health professionals are important in this process, as it is a phenomenon with repercussions in health. Because they work in the Family Health Strategy, which focuses on the prevention of harm and illness, health promotion and interdepartmentality, the nurses are essential in the process of preventing and confronting this phenomenon.

  5. Women experiencing the intergenerationality of conjugal violence.

    Science.gov (United States)

    Paixão, Gilvânia Patrícia do Nascimento; Gomes, Nadirlene Pereira; Diniz, Normélia Maria Freire; Carvalho e Lira, Margaret Ollinda de Souza; Carvalho, Milca Ramaiane da Silva; da Silva, Rudval Souza

    2015-01-01

    to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence. qualitative study. Interviews were held with 19 women, who were experiencing conjugal violence, and who were resident in a community in Salvador, Bahia, Brazil. The project was approved by the Research Ethics Committee (N. 42/2011). the data was organized using the Discourse of the Collective Subject, identifying the summary central ideas: they witnessed violence between their parents; they suffered repercussions from the violence between their parents: they were angry about the mother's submission to her partner; and they reproduced the conjugal violence. The discourse showed that the women witnessed, in childhood and adolescence, violence between their parents, and were injured both physically and psychologically. As a result of the mother's submission, feelings of anger arose in the children. However, in the adult phase of their own lives, they noticed that their conjugal life resembled that of their parents, reproducing the violence. investment is necessary in strategies designed to break inter-generational violence, and the health professionals are important in this process, as it is a phenomenon with repercussions in health. Because they work in the Family Health Strategy, which focuses on the prevention of harm and illness, health promotion and interdepartmentality, the nurses are essential in the process of preventing and confronting this phenomenon.

  6. Unsymmetrical extended -conjugated zinc phthalocyanine for ...

    Indian Academy of Sciences (India)

    We have designed and synthesized a new unsymmetrical zinc phthalocyanine based on `push-pull' and extended -conjugation concept, PCH008. The new sensitizer was fully characterized by CHN anlysis, UV-Vis., fluorescence spectroscopies and cyclic voltammetry. The new sensitizer which upon anchoring onto ...

  7. Compositions for directed alignment of conjugated polymers

    Science.gov (United States)

    Kim, Jinsang; Kim, Bong-Gi; Jeong, Eun Jeong

    2016-04-19

    Conjugated polymers (CPs) achieve directed alignment along an applied flow field and a dichroic ratio of as high as 16.67 in emission from well-aligned thin films and fully realized anisotropic optoelectronic properties of CPs in field-effect transistor (FET).

  8. Theoretical study of conjugated porphyrin polymers

    DEFF Research Database (Denmark)

    Pedersen, T.G.; Lynge, T.B.; Kristensen, P.K.

    2005-01-01

    for these applications. From a theoretical analysis of excitons in long metalloporphyrin chains, we demonstrate that the binding energy is much lower than in usual conjugated polymers. Our calculated absorption spectra are in good agreement with measurements. (c) 2004 Elsevier B.V. All rights reserved....

  9. preconditioning the modified conjugate gradient method

    African Journals Online (AJOL)

    Admin

    The conventional conjugate method (CGM) was originally developed by Hestenes and. Stiefel (1952) as a method of solution for linear systems. Fletcher and Reeves (1964) built the necessary underlying theory for a successful application of the method to quadratic functional and developed its convergence properties.

  10. Ciprofloxacin conjugated zinc oxide nanoparticle: A camouflage ...

    Indian Academy of Sciences (India)

    excellent antibacterial activity against clinically isolated multidrug resistant bacterial strains of Escherichia coli,. Staphylococcus aureus and ... Keywords. Zinc oxide nanoparticles; ciprofloxacin; chemical conjugation; antibacterial property. 1. Introduction ... Nanoparticles of TiO2, ZnO, silver, etc. are commonly known for their ...

  11. Bacillus thuringiensis Conjugation in Simulated Microgravity

    Science.gov (United States)

    Beuls, Elise; van Houdt, Rob; Leys, Natalie; Dijkstra, Camelia; Larkin, Oliver; Mahillon, Jacques

    2009-10-01

    Spaceflight experiments have suggested a possible effect of microgravity on the plasmid transfer among strains of the Gram-positive Bacillus thuringiensis, as opposed to no effect recorded for Gram-negative conjugation. To investigate these potential effects in a more affordable experimental setup, three ground-based microgravity simulators were tested: the Rotating Wall Vessel (RWV), the Random Positioning Machine (RPM), and a superconducting magnet. The bacterial conjugative system consisted in biparental matings between two B. thuringiensis strains, where the transfer frequencies of the conjugative plasmid pAW63 and its ability to mobilize the nonconjugative plasmid pUB110 were assessed. Specifically, potential plasmid transfers in a 0-g position (simulated microgravity) were compared to those obtained under 1-g (normal gravity) condition in each device. Statistical analyses revealed no significant difference in the conjugative and mobilizable transfer frequencies between the three different simulated microgravitational conditions and our standard laboratory condition. These important ground-based observations emphasize the fact that, though no stimulation of plasmid transfer was observed, no inhibition was observed either. In the case of Gram-positive bacteria, this ability to exchange plasmids in weightlessness, as occurs under Earth's conditions, should be seen as particularly relevant in the scope of spread of antibiotic resistances and bacterial virulence.

  12. Conjugated Polymer Actuators: Prospects and Limitations

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    Actuators constructed with a conjugated polymer as the active part have been predicted to have a number of highly desirable properties: Large mechanical strength, high power density, i.e. high actuation speeds possible, sufficient maximum strain values, high reversibility and safe, low voltages (1...

  13. Immunogenicity of novel sulfadimethoxide conjugates | Chen ...

    African Journals Online (AJOL)

    Immunogenicity of novel sulfadimethoxide conjugates. L Chen, J Su, X Zhang, L Li, X He. Abstract. Sulfadimethoxine (SDM) is an antibiotic commonly added to animal feeds. Anti-SDM antibodies are useful for the detection of residual SDM in foods, feeds and biological fluids by ELISA. In this study, we show that SDM is ...

  14. Theory of periodic conjugate heat transfer

    CERN Document Server

    Zudin, Yuri B

    2016-01-01

    This book presents the theory of periodic conjugate heat transfer in detail. It offers a simplified description of the interaction between a solid body and a fluid as a boundary value problem of the heat conduction equation for the solid body.

  15. Meningococcal conjugate vaccines: optimizing global impact

    Directory of Open Access Journals (Sweden)

    Terranella A

    2011-09-01

    Full Text Available Andrew Terranella1,2, Amanda Cohn2, Thomas Clark2 1Epidemic Intelligence Service, Division of Applied Sciences, Scientific Education and Professional Development Program Office, 2Meningitis and Vaccine Preventable Diseases Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country. Keywords: conjugate vaccine, meningitis, meningococcal vaccine, meningococcal disease

  16. One-pot synthesis of conjugated trienes

    Czech Academy of Sciences Publication Activity Database

    Šebesta, Petr; Jahn, Ullrich

    2009-01-01

    Roč. 103, č. 11 (2009), s. 990-990 ISSN 0009-2770. [Pokroky v organické, bioorganické a farmaceutické chemii /44./. 27.11.2009-29.11.2009, Liblice] Institutional research plan: CEZ:AV0Z40550506 Keywords : pheromones * Suzuki coupling * conjugated trienes Subject RIV: CC - Organic Chemistry

  17. Determinants of pneumococcal conjugate vaccine uptake among ...

    African Journals Online (AJOL)

    Subjects: The respondents were the parents/guardians of children less than two years of age attending immunisation services at KNH and those admitted in the peadiatric wards with pneumonia. Results: The study established that the determinants of uptake of Pneumococcal Conjugate Vaccine are age(OR 5.8, CI 1.4-23.4, ...

  18. Stabilizing cations in the backbones of conjugated polymers

    NARCIS (Netherlands)

    Voortman, Thomas P.; de Gier, Hilde D.; Havenith, Remco W. A.; Chiechi, Ryan C.

    2014-01-01

    We synthesized a cross-conjugated polymer containing ketones in the backbone and converted it to a linearly conjugated, cationic polyarylmethine via a process we call "spinless doping" to create a new class of materials, conjugated polyions. This process involves activating the ketones with a Lewis

  19. DA conjugated polymers containing substituted thiophene, 1, 3, 4 ...

    Indian Academy of Sciences (India)

    ... electron-accepting (A) 1,3,4- oxadiazole unit and non-conjugation linkers. The conjugated segment in P1-P3 contains only five aromatic rings resulting in short conjugation length, but has an alternate D-A arrangement which significantly enhances the intramolecular charge transfer (ICT) interaction within the segment.

  20. Conjugated Polymers and Oligomers: Structural and Soft Matter Aspects

    DEFF Research Database (Denmark)

    This book identifies modern topics and current trends of structural and soft matter aspects of conjugated polymers and oligomers. Each chapter recognizes an active research line where structural perspective dominates research and therefore the book covers fundamental aspects of persistent...... conjugated polymer backbone, water soluble conjugated polyelectrolytes and surfactants, conjugated molecules and biomolecules and DNA and the advanced use of synchrotron radiation and electron microscopy to find out structural details in conjugated molecule films and devices as well as under ambient...... and extreme conditions....

  1. Synthesis of gold and silver nanoparticle S-ovalbumin protein conjugates by in situ conjugation process

    Science.gov (United States)

    Joshi, Deepti; Soni, R. K.

    2015-05-01

    Pure gold and silver nanoparticle (NP) generation and their conjugation with protein S-ovalbumin using in situ conjugation process have been reported. The in situ conjugation involves nanosecond pulse laser ablation of pure metal target in the protein S-ovalbumin solution. Transmission electron microscopy (TEM) and UV-Visible absorption results show decrease in mean NP size along with narrow particle size distribution on ablation in S-ovalbumin solution as compared to ablation in water for both Au and Ag NPs. Also, the NP size reduction was found to be dependent on the concentration of S-ovalbumin. For AuNPs, spherical NPs of mean size 4 nm with particle size distribution 2-6 nm were obtained at 300 nM S-ovalbumin concentration. Further, it has been observed that the resultant in situ-conjugated colloid gold and silver NP solutions were quite stable even in the presence of NaCl at physiological salt concentration (0.15 M). On post-laser irradiation (532 nm, 15 mJ) for 20 min, 9 nm red shift in surface plasmon resonance peak (SPR), along with increased broadening towards longer wavelength, was observed in the AuNPs-S-ovalbumin sample. Further increase in the time of irradiation showed shift in AuNPs-S-ovalbumin SPR towards lower wavelength. On laser irradiation (532 nm, 15 mJ) for 20 min, no significant change was observed in the line shape of the plasmon absorption band of the AgNPs-S-ovalbumin conjugate. FTIR spectra revealed that S-ovalbumin peptide backbone and secondary structure remain unchanged on laser irradiation during in situ conjugation process. Thus, integrity of S-ovalbumin does not get affected, and no degradation of S-ovalbumin takes place on laser-induced in situ conjugation. Raman results confirm that both Au and Ag NPs interact with S-ovalbumin via thiol-bearing cysteine residues of the disulfide bond.

  2. General classes of double phase conjugation.

    Science.gov (United States)

    Sternklar, S

    1995-02-01

    The double phase-conjugate mirror (DPCM) is a stimulated four-wave mixing effect, mediated by either a chi(3) mechanism or a photorefractive effect. The type of grating that operates in the DPCM can be a transmission or reflection grating, depending on the wave-mixing configuration. Any combination of nonlinearity and grating geometry is possible, so that four general DPCM classes emerge. An analytic solution of the last unsolved class, the photorefractive reflection DPCM, is presented. With these results, general observations concerning the four categories of double phase conjugation are made. An important conclusion is that the type of grating geometry and its associated boundary conditions dictate many of the basic features of the DPCM, regardless of the nonlinearity involved.

  3. Stochastic Spectral and Conjugate Descent Methods

    KAUST Repository

    Kovalev, Dmitry

    2018-02-11

    The state-of-the-art methods for solving optimization problems in big dimensions are variants of randomized coordinate descent (RCD). In this paper we introduce a fundamentally new type of acceleration strategy for RCD based on the augmentation of the set of coordinate directions by a few spectral or conjugate directions. As we increase the number of extra directions to be sampled from, the rate of the method improves, and interpolates between the linear rate of RCD and a linear rate independent of the condition number. We develop and analyze also inexact variants of these methods where the spectral and conjugate directions are allowed to be approximate only. We motivate the above development by proving several negative results which highlight the limitations of RCD with importance sampling.

  4. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    International Nuclear Information System (INIS)

    Perkins, Alan; Hopper, Melanie; Murray, Andrea; Frier, Malcolm; Bishop, Mike

    2002-01-01

    The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C 595 (gG3) which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radio immuno conjugates of the C 595 antibody have been produced with high radiolabelling efficiency and immuno reactivity using Tc-99 m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun. (author)

  5. Towards an integrated model of bacterial conjugation.

    Science.gov (United States)

    Cabezón, Elena; Ripoll-Rozada, Jorge; Peña, Alejandro; de la Cruz, Fernando; Arechaga, Ignacio

    2015-01-01

    Bacterial conjugation is one of the main mechanisms for horizontal gene transfer. It constitutes a key element in the dissemination of antibiotic resistance and virulence genes to human pathogenic bacteria. DNA transfer is mediated by a membrane-associated macromolecular machinery called Type IV secretion system (T4SS). T4SSs are involved not only in bacterial conjugation but also in the transport of virulence factors by pathogenic bacteria. Thus, the search for specific inhibitors of different T4SS components opens a novel approach to restrict plasmid dissemination. This review highlights recent biochemical and structural findings that shed new light on the molecular mechanisms of DNA and protein transport by T4SS. Based on these data, a model for pilus biogenesis and substrate transfer in conjugative systems is proposed. This model provides a renewed view of the mechanism that might help to envisage new strategies to curb the threating expansion of antibiotic resistance. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  6. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  7. Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis.

    Science.gov (United States)

    Topuzogullari, Murat; Cakir Koc, Rabia; Dincer Isoglu, Sevil; Bagirova, Melahat; Akdeste, Zeynep; Elcicek, Serhat; Oztel, Olga N; Yesilkir Baydar, Serap; Canim Ates, Sezen; Allahverdiyev, Adil M

    2013-06-03

    Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.

  8. A natural variant of the cysteine protease virulence factor of group A Streptococcus with an arginine-glycine-aspartic acid (RGD) motif preferentially binds human integrins alphavbeta3 and alphaIIbbeta3.

    Science.gov (United States)

    Stockbauer, K E; Magoun, L; Liu, M; Burns, E H; Gubba, S; Renish, S; Pan, X; Bodary, S C; Baker, E; Coburn, J; Leong, J M; Musser, J M

    1999-01-05

    The human pathogenic bacterium group A Streptococcus produces an extracellular cysteine protease [streptococcal pyrogenic exotoxin B (SpeB)] that is a critical virulence factor for invasive disease episodes. Sequence analysis of the speB gene from 200 group A Streptococcus isolates collected worldwide identified three main mature SpeB (mSpeB) variants. One of these variants (mSpeB2) contains an Arg-Gly-Asp (RGD) sequence, a tripeptide motif that is commonly recognized by integrin receptors. mSpeB2 is made by all isolates of the unusually virulent serotype M1 and several other geographically widespread clones that frequently cause invasive infections. Only the mSpeB2 variant bound to transfected cells expressing integrin alphavbeta3 (also known as the vitronectin receptor) or alphaIIbbeta3 (platelet glycoprotein IIb-IIIa), and binding was blocked by a mAb that recognizes the streptococcal protease RGD motif region. In addition, mSpeB2 bound purified platelet integrin alphaIIbbeta3. Defined beta3 mutants that are altered for fibrinogen binding were defective for SpeB binding. Synthetic peptides with the mSpeB2 RGD motif, but not the RSD sequence present in other mSpeB variants, blocked binding of mSpeB2 to transfected cells expressing alphavbeta3 and caused detachment of cultured human umbilical vein endothelial cells. The results (i) identify a Gram-positive virulence factor that directly binds integrins, (ii) identify naturally occurring variants of a documented Gram-positive virulence factor with biomedically relevant differences in their interactions with host cells, and (iii) add to the theme that subtle natural variation in microbial virulence factor structure alters the character of host-pathogen interactions.

  9. Magnetic properties of CaCu{sub 5}-type RNi{sub 3}TSi (R=Gd and Tb, T=Mn, Fe, Co and Cu) compounds

    Energy Technology Data Exchange (ETDEWEB)

    Morozkin, A.V., E-mail: morozkin@tech.chem.msu.ru [Department of Chemistry, Moscow State University, Leninskie Gory, House 1, Building 3, GSP-2, Moscow 119992 (Russian Federation); Knotko, A.V. [Department of Chemistry, Moscow State University, Leninskie Gory, House 1, Building 3, GSP-2, Moscow 119992 (Russian Federation); Yapaskurt, V.O. [Department of Petrology, Geological Faculty, Moscow State University, Leninskie Gory, Moscow 119992 (Russian Federation); Yao, Jinlei [Research Center for Solid State Physics and Materials, School of Mathematics and Physics, Suzhou University of Science and Technology, Suzhou 215009 (China); Yuan, Fang; Mozharivskyj, Y. [Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1 (Canada); Nirmala, R. [Indian Institute of Technology Madras, Chennai 600036 (India); Quezado, S.; Malik, S.K. [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Natal 59082-970 (Brazil)

    2015-12-15

    Magnetic properties and magnetocaloric effect of CaCu{sub 5}-type RNi{sub 3}TSi (R=Gd and Tb, T=Mn, Fe, Co and Cu) compounds have been investigated. Magnetic measurements of RNi{sub 3}TSi display the increasing of Curie temperature and the decreasing of magnetocaloric effect and saturated magnetic moment in the row of ‘RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi’. In contrast to GdNi{sub 3}{Mn, Fe, Co}Si, TbNi{sub 3}{Mn, Fe, Co}Si exhibit significant magnetic hysteresis. The coercive field increases from TbNi{sub 4}Si (~0.5 kOe) to TbNi{sub 3}CoSi (4 kOe), TbNi{sub 3}MnSi (13 kOe) and TbNi{sub 3}FeSi (16 kOe) in field of 50 kOe at 5 K, whereas TbNi{sub 3}CuSi exhibits a negligible coercive field. - Graphical abstract: Magnetic measurements of RNi{sub 3}TSi show the increasing of Curie temperature and the decreasing of magnetocaloric effect and saturated magnetic moment in the row of 'RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi'. In contrast to GdNi{sub 3}{Mn, Fe, Co}Si, TbNi{sub 3}{Mn, Fe, Co}Si exhibit significant magnetic hysteresis. The coercive field increases from TbNi{sub 4}Si (~0.5 kOe) to TbNi{sub 3}CoSi (4 kOe), TbNi{sub 3}MnSi (13 kOe) and TbNi{sub 3}FeSi (16 kOe) in field of 50 kOe at 5 K, whereas TbNi{sub 3}CuSi exhibits a negligible coercive field. - Highlights: • CaCu{sub 5}-type RNi{sub 3}TSi show ferromagnetic ordering (R=Gd, Tb, T=Mn–Co, Cu). • Curie point increases in ‘RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi’ row. • MCE decreases in ‘RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi’ row. • TbNi{sub 3}{Mn, Fe, Co}Si exhibit significant magnetic hysteresis. • The coercive field of TbNi{sub 3}MnSi and TbNi{sub 3}FeSi reach 13 kOe and 16 kOe at 5 K.

  10. Co-conjugation vis-à-vis individual conjugation of α-amylase and glucoamylase for hydrolysis of starch.

    Science.gov (United States)

    Jadhav, Swati B; Singhal, Rekha S

    2013-10-15

    Two enzymes, α-amylase and glucoamylase have been individually and co-conjugated to pectin by covalent binding. Both the enzyme systems showed better thermal and pH stability over the free enzyme system with the complete retention of original activities. Mixture of individually conjugated enzymes showed lower inactivation rate constant with longer half life than the co-conjugated enzyme system. Individually conjugated enzymes showed an increase of 56.48 kJ/mole and 38.22 kJ/mole in activation energy for denaturation than the free enzymes and co-conjugated enzymes, respectively. Km as well as Vmax of individually and co-conjugated enzymes was found to be higher than the free enzymes. SDS-polyacrylamide gel electrophoresis confirmed the formation of conjugate and co-conjugate as evident by increased molecular weight. Both the enzyme systems were used for starch hydrolysis where individually conjugated enzymes showed highest release of glucose at 60 °C and pH 5.0 as compared to free and co-conjugated enzyme. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Reflection and transmission of twisted light at phase conjugating interfaces.

    Science.gov (United States)

    Thakur, Anita; Berakdar, Jamal

    2012-01-16

    We study the transmission and the reflection of light beams carrying orbital angular momentum through a dielectric multilayer structure containing phase-conjugating interfaces. We show analytically and demonstrate numerically that the phase conjugation at the interfaces results in a characteristic angular and radial pattern of the reflected beam, a fact that can be exploited for the detection and the characterization of phase conjugation in composite optical materials.

  12. Evolution of conjugation and type IV secretion systems.

    Science.gov (United States)

    Guglielmini, Julien; de la Cruz, Fernando; Rocha, Eduardo P C

    2013-02-01

    Genetic exchange by conjugation is responsible for the spread of resistance, virulence, and social traits among prokaryotes. Recent works unraveled the functioning of the underlying type IV secretion systems (T4SS) and its distribution and recruitment for other biological processes (exaptation), notably pathogenesis. We analyzed the phylogeny of key conjugation proteins to infer the evolutionary history of conjugation and T4SS. We show that single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) conjugation, while both based on a key AAA(+) ATPase, diverged before the last common ancestor of bacteria. The two key ATPases of ssDNA conjugation are monophyletic, having diverged at an early stage from dsDNA translocases. Our data suggest that ssDNA conjugation arose first in diderm bacteria, possibly Proteobacteria, and then spread to other bacterial phyla, including bacterial monoderms and Archaea. Identifiable T4SS fall within the eight monophyletic groups, determined by both taxonomy and structure of the cell envelope. Transfer to monoderms might have occurred only once, but followed diverse adaptive paths. Remarkably, some Firmicutes developed a new conjugation system based on an atypical relaxase and an ATPase derived from a dsDNA translocase. The observed evolutionary rates and patterns of presence/absence of specific T4SS proteins show that conjugation systems are often and independently exapted for other functions. This work brings a natural basis for the classification of all kinds of conjugative systems, thus tackling a problem that is growing as fast as genomic databases. Our analysis provides the first global picture of the evolution of conjugation and shows how a self-transferrable complex multiprotein system has adapted to different taxa and often been recruited by the host. As conjugation systems became specific to certain clades and cell envelopes, they may have biased the rate and direction of gene transfer by conjugation within prokaryotes.

  13. Genetic drift suppresses bacterial conjugation in spatially structured populations

    OpenAIRE

    Freese, Peter D.; Korolev, Kirill S.; Jimenez, Jose I.; Chen, Irene A.

    2014-01-01

    Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid ag...

  14. Design, synthesis, characterization and study of novel conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wu [Iowa State Univ., Ames, IA (United States)

    1997-06-24

    After introducing the subject of conjugated polymers, the thesis has three sections each containing a literature survey, results and discussion, conclusions, and experimental methods on the following: synthesis, characterization of electroluminescent polymers containing conjugated aryl, olefinic, thiophene and acetylenic units and their studies for use in light-emitting diodes; synthesis, characterization and study of conjugated polymers containing silole unit in the main chain; and synthesis, characterization and study of silicon-bridged and butadiene-linked polythiophenes.

  15. Magnetic Field Effect in Conjugated Molecules-Based Devices

    Science.gov (United States)

    2017-10-23

    AFRL-AFOSR-JP-TR-2017-0073 Magnetic field effect in conjugated molecules-based devices Tzung-Fang Guo NATIONAL CHENG KUNG UNIVERSITY Final Report 10...Final 3. DATES COVERED (From - To) 22 Jul 2014 to 21 Jul 2017 4. TITLE AND SUBTITLE Magnetic field effect in conjugated molecules-based devices 5a... Magnetic field effect in conjugated molecule-based devices. The final year of the project had a collaboration with Professor Bin Hu at the University

  16. Effect of Fatty Acid Conjugation on Antimicrobial Peptide Activity

    National Research Council Canada - National Science Library

    Chu-Kung, Alexander F; Bozzelli, Kristen N; Nguyen, Rose; Tirrell, Matthew V

    2004-01-01

    ... or the conjugate of the nonamphipathic peptide, KAK. The induction of helicity corresponds to a significant improvement in antimicrobial activity as measured by a minimum bactericidal concentration test...

  17. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

  18. Methotrexate and epirubicin conjugates as potential antitumor drugs

    Directory of Open Access Journals (Sweden)

    Szymon Wojciech Kmiecik

    2017-07-01

    Full Text Available Introduction: The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX and epirubicin (EPR. The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.Materials and methods: Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.Results: The conjugation reaction results in the formation of monosubstituted (α, γ and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.Discussion: Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.

  19. Interplay of alternative conjugated pathways and steric interactions on the electronic and optical properties of donor-acceptor conjugated polymers

    KAUST Repository

    Lima, Igo T.

    2014-01-01

    Donor-acceptor π-conjugated copolymers are of interest for a wide range of electronic applications, including field-effect transistors and solar cells. Here, we present a density functional theory (DFT) study of the impact of varying the conjugation pathway on the geometric, electronic, and optical properties of donor-acceptor systems. We consider both linear ("in series"), traditional conjugation among the donor-acceptor moieties versus structures where the acceptor units are appended orthogonally to the linear, donor-only conjugated backbone. Long-range-corrected hybrid functionals are used in the investigation with the values of the tuned long-range separation parameters providing an estimate of the extent of conjugation as a function of the oligomer architecture. Considerable differences in the electronic and optical properties are determined as a function of the nature of the conjugation pathway, features that should be taken into account in the design of donor-acceptor copolymers.

  20. Multicellular computing using conjugation for wiring.

    Science.gov (United States)

    Goñi-Moreno, Angel; Amos, Martyn; de la Cruz, Fernando

    2013-01-01

    Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal "re-programming" and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a "computation" is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the "wiring" between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing

  1. Multicellular Computing Using Conjugation for Wiring

    Science.gov (United States)

    Goñi-Moreno, Angel; Amos, Martyn; de la Cruz, Fernando

    2013-01-01

    Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal “re-programming” and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a “computation” is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the “wiring” between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular

  2. Polar reactions of acyclic conjugated bisallenes

    Directory of Open Access Journals (Sweden)

    Reiner Stamm

    2013-01-01

    Full Text Available The chemical behaviour of various alkyl-substituted, acyclic conjugated bisallenes in reactions involving polar intermediates and/or transition states has been investigated on a broad scale for the first time. The reactions studied include lithiation, reaction of the thus formed organolithium salts with various electrophiles (among others, allyl bromide, DMF and acetone, oxidation to cyclopentenones and epoxides, hydrohalogenation (HCl, HBr addition, halogenation (Br2 and I2 addition, and [2 + 2] cycloaddition with chlorosulfonyl isocyanate. The resulting adducts were fully characterized by spectroscopic and analytical methods; they constitute interesting substrates for further organic transformations.

  3. Modeling Transformation and Conjugation in Bacteria Populations

    Science.gov (United States)

    Russo, John; Dong, J. J.

    The rise of antibiotic resistance in bacteria populations is a growing threat to medical treatment of diseases. Transformation, where a cell absorbs a plasmid from its environment, and conjugation, direct transfer of a plasmid from one cell to another, are the two main mechanisms of emergence of antibiotic resistance. We model the processes using a combined approach of Kinetic Monte Carlo simulation and differential equations to describe the plasmid-carrying and plasmid-free populations. Through analysis of our results, we characterize the conditions that lead to dominance of the antibiotic resistant population. NSF-DMR #1248387.

  4. HPMA copolymer conjugates for dual therapy

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Krakovičová, Hana; Šírová, Milada; Říhová, Blanka; Ulbrich, Karel

    2008-01-01

    Roč. 132, č. 3 (2008), s. 63-65 ISSN 0168-3659. [European Symposium on Controlled Drug Delivery /10./. Noordwijk an Zee, 02.04.2008-04.04.2008] R&D Projects: GA MŠk 1M0505; GA AV ČR IAA400500806 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : dual therapy * polymer conjugates * controlled release Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.690, year: 2008

  5. Rhenium 188 labelling of peptide conjugates

    International Nuclear Information System (INIS)

    Melendez-Alafort, Laura

    2001-01-01

    Many human tumours express high levels, of somatostatin receptors. In order to make possible a radiotherapeutic treatment of this kind for tumour a series of somatostatin analogues that can tightly chelate beta emitting isotopes have been developed in recent years. The work carried out for this thesis has been aimed towards development of a new therapeutic radiopharmaceutical for treatment of somatostatin receptor positive tumours. The first chapters describe work with technetium-99m to establish the labelling and analytical conditions for a somatostatin analogue, [Tyr 3 ]-octreotide (TOC), as a precursor to undertaking labelling studies with the beta emitter rhenium-188. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was conjugated to TOC and labelled with 99m using different coligands. Then the stability, receptor binding and biodistribution of each complex were assessed. 99m Tc-HYNIC-TOC using EDDA as coligand showed the best characteristics, and was superior for tumour imaging in humans than the commercially available 111 In-DTPA-octreotide. The conditions for labelling the HYNIC-TOC conjugate with 188 Re were then optimised using tricine as a co-ligand. A labelling yield of ∼80% was achieved. After purification however, the stability of the complex was low. The use of other coligand systems which had proved useful for 99m Tc labelling was explored, but yields were very poor. Other chelators such as diethylenetriamine pentaacetic acid (DTPA), dimercaptosuccinic acid (DMSA) and mercaptoacetyltriglycine (MAG 3 ) were studied as potential co-ligand agents to label the HYNIC-TOC conjugate with 188 Re but, again low yields of the labelled peptide complexes were achieved. A novel 188 Re-HYNIC complex was prepared in high yields using N-N-disubstituted dithiocarbamates as coligands. However to date, the specific activities achieved with this system are relatively low. The use of the [ 99m Tc(CO) 3 (H 2 O) 3 ] complex to label the HYNIC-TOC conjugate was investigated

  6. Evaluation of Haemophilus influenzae Type B Conjugate Vaccine (Meningococcal Protein Conjugate in Canadian Infants

    Directory of Open Access Journals (Sweden)

    David W Scheifele

    1994-01-01

    Full Text Available Objective: To assess adverse effects and immune responses with a three-dose series of Haemophilus influenzae type b meningococcal protein conjugate (PedvaxHIB or Hib.OMP vaccine, including any immunological response alterations from concurrent administration with routine vaccines for infants.

  7. Synthesis of gold and silver nanoparticle S-ovalbumin protein conjugates by in situ conjugation process

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Deepti, E-mail: deeptimishrajoshi@gmail.com; Soni, R. K. [Indian Institute of Technology Delhi, Physics Department (India)

    2015-05-15

    Pure gold and silver nanoparticle (NP) generation and their conjugation with protein S-ovalbumin using in situ conjugation process have been reported. The in situ conjugation involves nanosecond pulse laser ablation of pure metal target in the protein S-ovalbumin solution. Transmission electron microscopy (TEM) and UV–Visible absorption results show decrease in mean NP size along with narrow particle size distribution on ablation in S-ovalbumin solution as compared to ablation in water for both Au and Ag NPs. Also, the NP size reduction was found to be dependent on the concentration of S-ovalbumin. For AuNPs, spherical NPs of mean size 4 nm with particle size distribution 2–6 nm were obtained at 300 nM S-ovalbumin concentration. Further, it has been observed that the resultant in situ-conjugated colloid gold and silver NP solutions were quite stable even in the presence of NaCl at physiological salt concentration (0.15 M). On post-laser irradiation (532 nm, 15 mJ) for 20 min, 9 nm red shift in surface plasmon resonance peak (SPR), along with increased broadening towards longer wavelength, was observed in the AuNPs–S-ovalbumin sample. Further increase in the time of irradiation showed shift in AuNPs–S-ovalbumin SPR towards lower wavelength. On laser irradiation (532 nm, 15 mJ) for 20 min, no significant change was observed in the line shape of the plasmon absorption band of the AgNPs–S-ovalbumin conjugate. FTIR spectra revealed that S-ovalbumin peptide backbone and secondary structure remain unchanged on laser irradiation during in situ conjugation process. Thus, integrity of S-ovalbumin does not get affected, and no degradation of S-ovalbumin takes place on laser-induced in situ conjugation. Raman results confirm that both Au and Ag NPs interact with S-ovalbumin via thiol-bearing cysteine residues of the disulfide bond.

  8. Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity

    KAUST Repository

    Othman, Basmah A.

    2016-04-01

    ZnO nanoparticles (NPs) are reported to show a high degree of cancer cell selectivity with potential use in cancer imaging and therapy. Questions remain about the mode by which the ZnO NPs cause cell death, whether they exert an intra- or extracellular effect, and the resistance among different cancer cell types to ZnO NP exposure. The present study quantifies the variability between the cellular toxicity, dynamics of cellular uptake, and dissolution of bare and RGD (Arg-Gly-Asp)-targeted ZnO NPs by MDA-MB-231 cells. Compared to bare ZnO NPs, RGD-targeting of the ZnO NPs to integrin αvβ3 receptors expressed on MDA-MB-231 cells appears to increase the toxicity of the ZnO NPs to breast cancer cells at lower doses. Confocal microscopy of live MDA-MB-231 cells confirms uptake of both classes of ZnO NPs with a commensurate rise in intracellular Zn2+ concentration prior to cell death. The response of the cells within the population to intracellular Zn2+ is highly heterogeneous. In addition, the results emphasize the utility of dynamic and quantitative imaging in understanding cell uptake and processing of targeted therapeutic ZnO NPs at the cellular level by heterogeneous cancer cell populations, which can be crucial for the development of optimized treatment strategies.

  9. Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice

    Directory of Open Access Journals (Sweden)

    Wang YW

    2014-10-01

    Full Text Available You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD sequence (NIR QDs-RGD can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800 to the RGD peptide (QD800-RGD. QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection. phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen. The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including

  10. Multi-hop conjugation based bacteria nanonetworks.

    Science.gov (United States)

    Balasubramaniam, Sasitharan; Lio', Pietro

    2013-03-01

    Molecular communication is a new paradigm for nanomachines to exchange information, by utilizing biological mechanism and/or components to transfer information (e.g., molecular diffusion, neuronal networks, molecular motors). One possible approach for molecular communication is through the use of bacteria, which can act as carriers for DNA-based information, i.e., plasmids. This paper analyzes multi-hop molecular nanonetworks that utilize bacteria as a carrier. The proposed approach combines different properties of bacteria to enable multi-hop transmission, such as conjugation and chemotaxis-based motility. Various analyses have been performed, including the correlation between the success rate of plasmid delivery to the destination node, and the role of conjugation in enabling this; as well as analyses on the impact of large topology shapes (e.g., Grid, Random, and Scale-free) on the success rate of plasmid delivery for multiple source-destination nanonetworks. A further solution proposed in this paper is the application of antibiotics to act as filters on illegitimate messages that could be delivered by the bacteria. Our evaluation, which has been conducted through a series of simulations, has shown that numerous bacteria properties fit to properties required for communication networking (e.g., packet filtering, routing, addressing).

  11. Antibody-Conjugated Nanoparticles for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Manuel Arruebo

    2009-01-01

    Full Text Available Nanoscience and Nanotechnology have found their way into the fields of Biotechnology and Medicine. Nanoparticles by themselves offer specific physicochemical properties that they do not exhibit in bulk form, where materials show constant physical properties regardless of size. Antibodies are nanosize biological products that are part of the specific immune system. In addition to their own properties as pathogens or toxin neutralizers, as well as in the recruitment of immune elements (complement, improving phagocytosis, cytotoxicity antibody dependent by natural killer cells, etc., they could carry several elements (toxins, drugs, fluorochroms, or even nanoparticles, etc. and be used in several diagnostic procedures, or even in therapy to destroy a specific target. The conjugation of antibodies to nanoparticles can generate a product that combines the properties of both. For example, they can combine the small size of nanoparticles and their special thermal, imaging, drug carrier, or magnetic characteristics with the abilities of antibodies, such as specific and selective recognition. The hybrid product will show versatility and specificity. In this review, we analyse both antibodies and nanoparticles, focusing especially on the recent developments for antibody-conjugated nanoparticles, offering the researcher an overview of the different applications and possibilities of these hybrid carriers.

  12. Opto-electronic properties of charged conjugated molecules

    NARCIS (Netherlands)

    Fratiloiu, S.

    2007-01-01

    The aim of this thesis is to provide fundamental insight into the nature and opto-electronic properties of charge carriers on conjugated oligomers and polymers. Electronic structure, optical absorption properties and distribution of charge carriers along the chains of different conjugated materials

  13. Computation of conjugate depths in cubic-shape open channels ...

    African Journals Online (AJOL)

    Determining conjugate depths for a given discharge and initial depth requires the solution of a cubic equation for the conjugate depth and there are currently two approaches to avoiding this difficulty in general. One approach is to iteratively try different depths until one is obtained which gives the same value of the ...

  14. The Synthesis of Substituted Piperazine-cholesterol Conjugates for ...

    African Journals Online (AJOL)

    A small library of cholesterol-piperazine conjugates were synthesized by the reaction of cholesteryl chloroformate with a set of substituted piperazines in dichloromethane at room temperature. The conjugates, all obtained in good to excellent yields, were synthesized to be key components of nucleic acid transfection ...

  15. Preparation and characterization of microspheres of albumin-heparin conjugates

    NARCIS (Netherlands)

    Kwon, Glen S.; Bae, You Han; Kim, Sung Wan; Cremers, Harry; Cremers, H.F.M.; Feijen, Jan

    1991-01-01

    Albumin-heparin microspheres have been prepared as a new drug carrier. A soluble albumin-heparin conjugate was synthesized by forming amide bonds between human serum albumin and heparin. After purification the albumin-heparin conjugate was crosslinked in a water-in-oil emulsion to form

  16. Synthesis of sugars catalysed by microgel conjugated rabbit muscle ...

    African Journals Online (AJOL)

    Microgel has been prepared and covalently conjugated to rabbit muscle aldolase and employed to catalyse reactions between dihydroxyacetone phosphate, DHAP natural and non-natural acceptors aldehydes in aqueous, aqueous – organic solvents at ambient temperature. The microgel conjugated enzyme was found to ...

  17. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel K.; Andresen, Thomas Lars

    2010-01-01

    The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an...

  18. Dynamics of nonlinear oscillators with time-varying conjugate coupling

    Indian Academy of Sciences (India)

    We explore the dynamical consequences of time-varying conjugate coupling in a system of nonlinear oscillators. We analyze the behavior of coupled ... Conjugate coupling; time varying coupling. PACS Nos 05.45.Xt. 1. Introduction ..... MDS acknowledges the financial support from DST,. New Delhi. References. [1] L Glass ...

  19. Self-pumped phase-conjugate fiber-optic gyro.

    Science.gov (United States)

    McMichael, I; Yeh, P

    1986-10-01

    We describe a new type of phase-conjugate fiber-optic gyro that uses self-pumped phase conjugation. The selfpumped configuration is simpler than externally pumped configurations and permits the use of sensing fibers longer than the coherence length of the laser. A proof-of-principle demonstration of rotation sensing with the device is presented.

  20. Cross-conjugation and quantum interference : a general correlation?

    NARCIS (Netherlands)

    Valkenier, Hennie; Guedon, Constant M.; Markussen, Troels; Thygesen, Kristian S.; van der Molen, Sense J.; Hummelen, Jan C.

    2014-01-01

    We discuss the relationship between the pi-conjugation pattern, molecular length, and charge transport properties of molecular wires, both from an experimental and a theoretical viewpoint. Specifically, we focus on the role of quantum interference in the conductance properties of cross-conjugated

  1. Genetic Drift Suppresses Bacterial Conjugation in Spatially Structured Populations

    Science.gov (United States)

    Freese, Peter D.; Korolev, Kirill S.; Jiménez, José I.; Chen, Irene A.

    2014-02-01

    Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid agar, and we develop a quantitative understanding by spatial extension of traditional mass-action models. We found that spatial structure suppresses conjugation in surface-associated growth because strong genetic drift leads to spatial isolation of donor and recipient cells, restricting conjugation to rare boundaries between donor and recipient strains. These results suggest that ecological strategies, such as enforcement of spatial structure and enhancement of genetic drift, could complement molecular strategies in slowing the spread of antibiotic resistance genes.

  2. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in caco-2 cells

    NARCIS (Netherlands)

    Usta, M.; Wortelboer, H.M.; Vervoort, J.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, P.J. van; Cnubben, N.H.P.

    2007-01-01

    Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and

  3. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in Caco-2 cells

    NARCIS (Netherlands)

    Usta, M.; Wortelboer, H.M.; Vervoort, J.J.M.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, van P.J.; Cnubben, N.H.P.

    2007-01-01

    Curcumin, an alpha,beta-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional H-1 NMR

  4. Impact of Signal-Conjugate Wavelength Shift on Optical Phase Conjugation-based Transmission of QAM Signals

    DEFF Research Database (Denmark)

    Da Ros, Francesco; Lillieholm, Mads; Yankov, Metodi Plamenov

    2017-01-01

    The impact of signal-conjugate wavelength shift on nonlinearity compensation through optical phase conjugation is investigated for 64- and 256-QAM. Wavelength-shift independent achievable rate improvements between 0.2 and 0.3 bit/symbol are reported for shifts up to 30 nm in 500-km transmission....

  5. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  6. Conjugate Heat Transfer Study in Hypersonic Flows

    Science.gov (United States)

    Sahoo, Niranjan; Kulkarni, Vinayak; Peetala, Ravi Kumar

    2018-04-01

    Coupled and decoupled conjugate heat transfer (CHT) studies are carried out to imitate experimental studies for heat transfer measurement in hypersonic flow regime. The finite volume based solvers are used for analyzing the heat interaction between fluid and solid domains. Temperature and surface heat flux signals are predicted by both coupled and decoupled CHT analysis techniques for hypersonic Mach numbers. These two methodologies are also used to study the effect of different wall materials on surface parameters. Effectiveness of these CHT solvers has been verified for the inverse problem of wall heat flux recovery using various techniques reported in the literature. Both coupled and decoupled CHT techniques are seen to be equally useful for prediction of local temperature and heat flux signals prior to the experiments in hypersonic flows.

  7. Conjugated Linoleic Acid and Importance to Health

    Directory of Open Access Journals (Sweden)

    Canan Asal Ulus

    2017-01-01

    Full Text Available The development in science  technology and the researches made in the health field showed that nutrition increases the effectiveness of medical treatment as well as maintaining the human health and singularly effective in the treatment of certain diseases. In recent years, the importance of nutritional elements called ‘Functional foods’ has increased. Functional foods provide physiological benefits and can reduce the risk of chronic diseases beyond their nutritional benefits. One of these functional compounds is conjugated linoleic acid (CLA isomers which have significant effects on human health and previously have been demonstrated in the researches carried out on people and animals. CLA’s attracted more attention after detection of its body fat accumulation reducing, antidiabetic, immune system enhancing, arteriosclerosis reducing, bone mineralization increasing effects.

  8. Interfacial Widths of Conjugated Polymer Bilayers

    Energy Technology Data Exchange (ETDEWEB)

    NCSU; UC Berkeley; UCSB; Advanced Light Source; Garcia, Andres; Yan, Hongping; Sohn, Karen E.; Hexemer, Alexander; Nguyen, Thuc-Quyen; Bazan, Guillermo C.; Kramer, Edward J.; Ade, Harald

    2009-08-13

    The interfaces of conjugated polyelectrolyte (CPE)/poly[2-methoxy-5-(2{prime}-ethylhexyloxy)-p-phenylene vinylene] (MEH-PPV) bilayers cast from differential solvents are shown by resonant soft X-ray reflectivity (RSoXR) to be very smooth and sharp. The chemical interdiffusion due to casting is limited to less than 0.6 nm, and the interface created is thus nearly 'molecularly' sharp. These results demonstrate for the first time and with high precision that the nonpolar MEH-PPV layer is not much disturbed by casting the CPE layer from a polar solvent. A baseline is established for understanding the role of interfacial structure in determining the performance of CPE-based polymer light-emitting diodes. More broadly, we anticipate further applications of RSoXR as an important tool in achieving a deeper understanding of other multilayer organic optoelectronic devices, including multilayer photovoltaic devices.

  9. Charge Injection and Transport in Conjugated Polymers.

    Science.gov (United States)

    Malliaras, George

    2007-03-01

    We will overview the state-of-the-art in our understanding of charge injection and transport in conjugated polymers. We start by discussing the identifying characteristics of this class of materials, especially in relation with their structure and morphology. We follow by reviewing the advantages and limitations of experimental techniques that are used to probe charge transport. We then embark on a discussion of the fundamentals of charge transport in organics. We follow a didactic approach, where we start from transport in crystalline semiconductors and gradually introduce corrections for space charge effects, for the influence of disorder on mobility, for high charge densities, and for electric field-dependent charge densities. We compare with experimental data from polyfluorenes. We then shift our attention to charge injection. We review some of the recent theories and compared their predictions to experimental data, again from polyfluorenes. We close by proposing directions for future work.

  10. Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging.

    Science.gov (United States)

    Wang, Chung-Hsin; Huang, Yu-Fen; Yeh, Chih-Kuang

    2011-06-07

    Targeted ultrasound contrast agents can be prepared by some specific bioconjugation techniques. The biotin-avidin complex is an extremely useful noncovalent binding system, but the system might induce immunogenic side effects in human bodies. Previous proposed covalently conjugated systems suffered from low conjugation efficiency and complex procedures. In this study, we propose a covalently conjugated nanobubble coupling with nucleic acid ligands, aptamers, for providing a higher specific affinity for ultrasound targeting studies. The sgc8c aptamer was linked with nanobubbles through thiol-maleimide coupling chemistry for specific targeting to CCRF-CEM cells. Further improvements to reduce the required time and avoid the degradation of nanobubbles during conjugation procedures were also made. Several investigations were used to discuss the performance and consistency of the prepared nanobubbles, such as size distribution, conjugation efficiency analysis, and flow cytometry assay. Further, we applied our conjugated nanobubbles to ex vivo ultrasound targeted imaging and compared the resulting images with optical images. The results indicated the availability of aptamer-conjugated nanobubbles in targeted ultrasound imaging and the practicability of using a highly sensitive ultrasound system in noninvasive biological research.

  11. Vitamin Bc -Bearing Hydrophilic Photosensitizer Conjugate for Photodynamic Cancer Theranostics.

    Science.gov (United States)

    Kim, Jiyoung; Kim, Kyoung Sub; Park, Sin-jung; Na, Kun

    2015-08-01

    The accurate diagnosis and proper therapy for cancer are essential to improve the success rate of cancer treatment. Here, we demonstrated that the vitamin Bc -bearing hydrophilic photosensitizer conjugate folic acid-polyethylene glycol-pheophorbideA (FA-PEG-PheoA) has been synthesized for the intracellular diagnosis and photodynamic therapy of a tumor. The synthesized vitamin Bc -bearing hydrophilic photosensitizer conjugate has been characterized for the folic acid receptor expressing the ability to target tumor cells, which is facilitated by the chemical conjugation with folic acid. The vitamin Bc -bearing hydrophilic photosensitizer conjugate internalization mechanism was identified through a competitive inhibition test with free folic acid. We optimized the laser-sensitive, cytotoxicity changeable, vitamin Bc -bearing hydrophilic photosensitizer conjugate concentration, which is non-cytotoxic under normal conditions and specifically cytotoxic toward cancer cells (maximum 69.15%) under laser irradiation conditions used for theranostic agents. The cancer therapeutic and diagnosis effects of synthesized conjugate were confirmed in MDA-MB-231 cells and MDA-MB-231-bearing mice. As a result, the vitamin Bc -bearing hydrophilic photosensitizer conjugate exhibited a highly photodynamic therapeutic effect, which enabled the selective detection of a folic acid receptor expressing cancer using optical imaging. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Studies of phase-conjugate optical device concepts

    Science.gov (United States)

    McMichael, I. C.; Yeh, P. A.

    1989-03-01

    Phase-conjugate gyroscopy is a new area promising significant advances in state-of-the-art inertial navigation. This contract demonstrated the first phase-conjugate fiber-optic gyros (PCFOG's) and their ability to use low cost multimode fiber components. The development of the PCFOG is now at the stage where its sources of noise and drift can be isolated, and its competitiveness with conventional fiber optic gyros can be tested. To come to this stage in development, several scientific and technical issues had to be resolved. For example, to correct for the modal scrambling of multimode fibers, the theory and practice of polarization preserving conjugators that worked at milliwatt power levels had to be developed and tested. Another issue was the mutual coherence requirement for two beams interacting with a self-pumped conjugator that at first restricted the PCFOG from using the most desireable form of biasing (fast phase modulation). This issue was resolved only recently when a new class of phase conjugators (mutually pumped conjugators) was developed that have the ability to operate with mutually incoherent beams. Almost as quickly as the first mutually pumped conjugators were discovered, this contract demonstrated the first PCFOG to use one. In addition to, and in the process of developing the PCFOG, this contract investigated several new photorefractive phenomena.

  13. Synthesis and antimicrobial activity of gold nanoparticle conjugates with cefotaxime

    Science.gov (United States)

    Titanova, Elena O.; Burygin, Gennady L.

    2016-04-01

    Gold nanoparticles (GNPs) have attracted significant interest as a novel platform for various applications to nanobiotechnology and biomedicine. The conjugates of GNPs with antibiotics and antibodies were also used for selective photothermal killing of protozoa and bacteria. Also the conjugates of some antibiotics with GNPs decreased the number of bacterial growing cells. In this work was made the procedure optimization for conjugation of cefotaxime (a third-generation cephalosporin antibiotic) with GNPs (15 nm) and we examined the antimicrobial properties of this conjugate to bacteria culture of E. coli K-12. Addition of cefotaxime solution to colloidal gold does not change their color and extinction spectrum. For physiologically active concentration of cefotaxime (3 μg/mL), it was shown that the optimum pH for the conjugation was more than 9.5. A partial aggregation of the GNPs in saline medium was observed at pH 6.5-7.5. The optimum concentration of K2CO3 for conjugation cefotaxime with GNPs-15 was 5 mM. The optimum concentration of cefotaxime was at 0.36 μg/mL. We found the inhibition of the growth of E. coli K12 upon application cefotaxime-GNP conjugates.

  14. Methods to Design and Synthesize Antibody-Drug Conjugates (ADCs

    Directory of Open Access Journals (Sweden)

    Houzong Yao

    2016-02-01

    Full Text Available Antibody-drug conjugates (ADCs have become a promising targeted therapy strategy that combines the specificity, favorable pharmacokinetics and biodistributions of antibodies with the destructive potential of highly potent drugs. One of the biggest challenges in the development of ADCs is the application of suitable linkers for conjugating drugs to antibodies. Recently, the design and synthesis of linkers are making great progress. In this review, we present the methods that are currently used to synthesize antibody-drug conjugates by using thiols, amines, alcohols, aldehydes and azides.

  15. CONJUGATED POLYMERS AND POLYELECTROLYTES IN SOLAR PHOTOCONVERSION, Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Schanze, Kirk S [University of Florida

    2014-08-05

    This DOE-supported program investigated the fundamental properties of conjugated polyelectrolytes, with emphasis placed on studies of excited state energy transport, self-assembly into conjugated polyelectroyte (CPE) based films and colloids, and exciton transport and charge injection in CPE films constructed atop wide bandgap semiconductors. In the most recent grant period we have also extended efforts to examine the properties of low-bandgap donor-acceptor conjugated polyelectrolytes that feature strong visible light absorption and the ability to adsorb to metal-oxide interfaces.

  16. Site-Selective Conjugation of Native Proteins with DNA

    DEFF Research Database (Denmark)

    Trads, Julie Brender; Tørring, Thomas; Gothelf, Kurt Vesterager

    2017-01-01

    -protein conjugates. In DNA nanotechnology, the DNA handle is exploited to precisely position proteins by self-assembly. For these applications, site-selective conjugation is almost always desired because fully functional proteins are required to maintain the specificity of antibodies and the activity of enzymes...... because approximately one-third of all wild-type proteins contain metal-binding sites, including many IgG antibodies, and it is also applicable to His-tagged proteins. This emerging field provides direct access to site-selective conjugates of DNA to commercially available proteins. In this Account, we...

  17. A qualidade conjugal e os estilos educativos parentais

    OpenAIRE

    Mosmann, Clarisse Pereira

    2007-01-01

    Esta Tese de Doutorado investiga a relação entre a qualidade do relacionamento conjugal e os estilos educativos parentais. O trabalho é apresentado na forma de artigos, sendo um artigo de revisão crítica da literatura e dois artigos empíricos, preparados para serem encaminhados para periódico científico. O primeiro artigo apresenta uma revisão teórica da literatura na área da qualidade conjugal. Este artigo buscou definir o conceito de qualidade conjugal e para tanto analisou-se sete teorias ...

  18. Conjugation vs hyperconjugation in molecular structure of acrolein

    Science.gov (United States)

    Shishkina, Svitlana V.; Slabko, Anzhelika I.; Shishkin, Oleg V.

    2013-01-01

    Analysis of geometric parameters of butadiene and acrolein reveals the contradiction between the Csp2-Csp2 bond length in acrolein and classical concept of conjugation degree in the polarized molecules. In this Letter the reasons of this contradiction have been investigated. It is concluded that the Csp2-Csp2 bond length in acrolein is determined by influence of the bonding for it π-π conjugation and antibonding n → σ∗ hyperconjugation between the oxygen lone pair and the antibonding orbital of the single bond. It was shown also this bond length depends on the difference in energy of conjugative and hyperconjugative interactions.

  19. Enhanced solubility and antioxidant activity of chlorogenic acid-chitosan conjugates due to the conjugation of chitosan with chlorogenic acid.

    Science.gov (United States)

    Rui, Liyun; Xie, Minhao; Hu, Bing; Zhou, Li; Saeeduddin, Muhammad; Zeng, Xiaoxiong

    2017-08-15

    Chlorogenic acid-chitosan conjugate was synthesized by introducing of chlorogenic acid onto chitosan with the aid of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxybenzotriazole. The data of UV-vis, FT-IR and NMR for chlorogenic acid-chitosan conjugates demonstrated the successful conjugation of chlorogenic acid with chitosan. Compared to chitosan, chlorogenic acid-chitosan conjugates exhibited increased solubility in distilled water, 1% acetic acid solution (v/v) or 50% ethanol solution (v/v) containing 0.5% acetic acid. Moreover, chlorogenic acid-chitosan conjugates showed dramatic enhancements in metal ion chelating activity, total antioxidant capacity, scavenging activities on 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) and superoxide radicals, inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching, and protective effect on H 2 O 2 -induced oxidative injury of PC12 cells. Particularly, chlorogenic acid-chitosan conjugate exhibited higher inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching than chlorogenic acid. The results suggested that chlorogenic acid-chitosan conjugates could serve as food supplements to enhance the function of foods in future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Preparation and characterization of a hetero functional system of gold nanoparticles labeled with 99mTc and conjugated to the sequence Arg-Gly-Asp for detection in vivo of angio genesis and evaluation of their toxicity in Hyalella aztec

    International Nuclear Information System (INIS)

    Morales A, E.

    2012-01-01

    Integrin s play critical roles in many physiological processes including angio genesis and also contribute to pathological events such as tumor invasion and metastasis. The α v β 3 integrin is expressed in normal endothelial cells but it is over-expressed in the tumor neo vasculature. Peptides based on the Arginine-Glycine-Aspartic acid (RGD) sequence have been reported as molecules with high affinity and selectivity for the α v β 3 integrin. Recent studies have demonstrated that conjugating peptides to gold nanoparticles (AuNP) produces biocompatible and stable multifunctional systems with target-specific molecular recognition due to multivalent effects produced by multiple simultaneous interactions between peptides and their receptors. The first aim of this research was to prepare a m ultimeric system of 99m Tc labeled gold particles conjugated to c[RGDfK(C)] and to evaluate its biological behavior as a potential radiopharmaceutical for molecular imaging of α v β 3 tumor expression. Hidrazinonicotinamide-G GC (HYNIC-G GC) and C[RGDfK(C)] peptides were synthesized and conjugated to AuNP (20 nm) by means of spontaneous reaction of the thiol groups of cysteine. The nano conjugate was characterized by transmission electron microscopy, Fourier transform-infrared, Ultraviolet-vis, X-ray photoelectron spectroscopy and Raman spectroscopy. To obtain 99m Tc-HYNIC-G GC-AuNP-c[RGDfK(C)], the 99m Tc-HYNIC-G GC radio peptide was first prepared and added to the AuNP solution followed by c[RGDfK(C)]. Radiochemical purity (Rp) was determined by size-exclusion HPLC and I TLC-Sg analyses. In vitro binding studies were carried out in α v β 3 receptor-positive C6 glioma cancer cells. Biodistribution studies were accomplished in athymic mice with C6-induced tumors with blocked and non blocked receptors, and images were obtained using a micro-SPECT/CT. Transmission electron microscopy and spectroscopy techniques demonstrated that AuNP were functionalized with peptides. Rp was

  1. Libraries of RGD analogs, labeled through ReO3+ or TcO3+ coordination, targeting αVβ3 integrin: development of tracers for the early detection of tumor neo-angiogenesis

    International Nuclear Information System (INIS)

    Aufort, M.

    2008-11-01

    Integrins form a family of hetero-dimeric integral glycoproteins which play a central role in cell-cell adhesion and cell-matrix interactions. In particular, they are over expressed during tumor neo-angiogenesis. About 10 of them recognize a structured RGD (Arg-Gly-Asp) sequence. Analogs of this sequence can be used for the early detection of tumors and metastases. We developed new tracers, labeled with 99m Tc, for the molecular imaging of α V β 3 integrin. Until recently, there was no reliable ab initio structure prediction of complex molecules containing Re and Tc chelates. Therefore, we preferred a combinatorial approach to develop potential ligands of α V β 3 integrin and we attempted to identify efficient tracers by in vivo screening. This method would account for biodistribution and pharmacokinetics properties in the early steps of the study. Tracers were obtained according two strategies: i) cyclization of linear RGD analogs; ii) combinatorial assembling of independent modules through metal core coordination by the well-known NS 2 +S motif. After synthesis and labeling, the stability of the tracers was investigated in presence of glutathione and in murine plasma. In vitro screening on purified integrin showed that a cyclic rhenium coordinate binds specifically α V β 3 . A tumor model (U87-MG tumor on nude mice) was validated in the laboratory and a method was developed to analyze in vivo experiments. Biodistribution data and percentage of activity found in tumors are encouraging for cyclic compounds though identification of efficient tracers is difficult due to their instability in the conditions of analyses. (author)

  2. Conjugation by Mosquito Pathogenic Strains of Bacillus sphaericus

    Directory of Open Access Journals (Sweden)

    Margarita Correa

    1997-05-01

    Full Text Available A mosquito pathogenic strain of Bacillus sphaericus carried out the conjugal transfer of plasmid pAMß1 to other strains of its own and two other serotypes. However, it was unable to conjugate with mosquito pathogens from three other serotypes, with B. sphaericus of other DNA homology groups or with three other species of Bacillus. Conjugation frequency was highest with a strain having an altered surface layer (S layer. Conjugal transfer of pAMß1 was not detected in mosquito larval cadavers. B. sphaericus 2362 was unable to mobilize pUB110 for transfer to strains that had served as recipients of pAMß1. These observations suggest that it is unlikely that genetically engineered B. sphaericus carrying a recombinant plasmid could pass that plasmid to other bacteria

  3. Effect of Fatty Acid Conjugation on Antimicrobial Peptide Activity

    National Research Council Canada - National Science Library

    Chu-Kung, Alexander F; Bozzelli, Kristen N; Nguyen, Rose; Tirrell, Matthew V

    2004-01-01

    .... In the presence of bacteria-mimicking phospholipid vesicles fatty acid conjugates of the amphipathic peptide, AKK, show a larger change in helical structure than either of the unmodified peptides...

  4. Evaluation of mutagenic/antimutagenic activity of conjugated linoleic ...

    African Journals Online (AJOL)

    Evaluation of mutagenic/antimutagenic activity of conjugated linoleic acid in mice by micronucleus test. LBD Carvalho-Silva, MDV Oliveira, DT Konichi, MR Maróstica JR, PCB Lollo, J Amaya-Farfán ...

  5. Intergenic and intragenic conjugal transfer of multiple antibiotic ...

    African Journals Online (AJOL)

    intragenic) in combination with sulphamethoxazole-trimethoprim (SXT), streptomycin and erythromycin as a self transposable tetracycline element. In intergenic transfer, conjugation frequency was more than intragenic transfer. Frequencies of ...

  6. On conjugate points and the Leitmann equivalent problem approach

    NARCIS (Netherlands)

    Wagener, F.O.O.

    2010-01-01

    This article extends the Leitmann equivalence method to a class of problems featuring conjugate points. The class is characterised by the requirement that the set of indifference points of a given problem forms a finite stratification.

  7. On conjugate points and the Leitmann equivalent problem approach

    NARCIS (Netherlands)

    Wagener, F.O.O.

    2009-01-01

    This article extends the Leitmann equivalence method to a class of problems featuring conjugate points. The class is characterised by the requirement that the set of indifference points of a given problem forms a finite stratification.

  8. Factors contributing to the immunogenicity of meningococcal conjugate vaccines

    Science.gov (United States)

    Bröker, Michael; Berti, Francesco; Costantino, Paolo

    2016-01-01

    ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310

  9. BSA-boronic acid conjugate as lectin mimetics.

    Science.gov (United States)

    Narla, Satya Nandana; Pinnamaneni, Poornima; Nie, Huan; Li, Yu; Sun, Xue-Long

    2014-01-10

    We report bovine serum albumin (BSA)-boronic acid (BA) conjugates as lectin mimetics and their glyco-capturing capacity. The BSA-BA conjugates were synthesized by amidation of carboxylic acid groups in BSA with aminophenyl boronic acid in the presence of EDC, and were characterized by Alizarin Red S (ARS) assay and SDS-PAGE gel. The BSA-BA conjugates were immobilized onto maleimide-functionalized silica beads and their sugar capturing capacity and specificity were confirmed by ARS displacement assay. Further, surface plasmon resonance (SPR) analysis of the glyco-capturing activity of the BSA-BA conjugates was conducted by immobilizing BSA-BA onto SPR gold chip. Overall, we demonstrated a BSA-BA-based lectin mimetics for glyco-capturing applications. These lectin mimetics are expected to provide an important tool for glycomics and biosensor research and applications. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Pneumococcal Conjugate Vaccine (PCV13): What You Need to Know

    Science.gov (United States)

    ... drugs. This makes prevention of the disease, through vaccination, even more important. 2 PCV13 vaccine Pneumococcal conjugate vaccine (called PCV13) protects against 13 types of pneumococcal bacteria. PCV13 is routinely given to ...

  11. Pneumococcal conjugate vaccine (PCV13) - What you need to know

    Science.gov (United States)

    ... drugs. This makes prevention of the disease, through vaccination, even more important. 2. PCV13 vaccine Pneumococcal conjugate vaccine (called PCV13) protects against 13 types of pneumococcal bacteria. PCV13 is routinely given to ...

  12. Photoresponsive peptide azobenzene conjugates that specifically interact with platinum surfaces

    Science.gov (United States)

    Dinçer, S.; Tamerler, C.; Sarıkaya, M.; Pişkin, E.

    2008-05-01

    The aim of this study is to prepare photoresponsive peptide-azobenzene compounds which interacts with platinum surfaces specifically, in order to create smart surfaces for further novel applications in design of smart biosensors and array platforms. Here, a water-soluble azobenzene molecule, 4-hydroxyazo benzene,4-sulfonic acid was synthesized by diazo coupling reaction. A platinum-specific peptide, originally selected by a phage display technique was chemically synthesized/purchased, and conjugated with the azobenzene compound activated with carbonyldiimidazole. Both azobenzene and its conjugate were characterized (including photoresponsive properties) by FTIR, NMR, and UV-spectrophotometer. The yield of conjugation reaction estimated by ninhydrin assay was about 65%. Peptide incorporation did not restrict the light-sensitivity of azobenzene. Adsorption of both the peptide and its azobenzene conjugate was followed by Quartz Crystal Microbalance (QCM) system. The kinetic evaluations exhibited that both molecules interact platinum surfaces, quite rapidly and strongly.

  13. Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine.

    Science.gov (United States)

    Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Anwar, Ayaz; Shah, Muhammad Raza; Khan, Naveed Ahmed

    2015-12-14

    Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth

  14. Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine

    Science.gov (United States)

    Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Anwar, Ayaz; Shah, Muhammad Raza

    2015-01-01

    Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth

  15. Inter-heterogeneity and intra-heterogeneity of α{sub v}β{sub 3} in non-small cell lung cancer and small cell lung cancer patients as revealed by {sup 68}Ga-RGD{sub 2} PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Fei; Li, Guoquan; Wang, Shengjun; Liu, Daliang; Zhang, Mingru; Zhao, Mingxuan; Yang, Weidong; Wang, Jing [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Wang, Zhe [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Fourth Military Medical University, Department of Pathology, Xijing Hospital, Xi' an (China)

    2017-08-15

    Integrin α{sub v}β{sub 3} is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare α{sub v}β{sub 3} levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer {sup 68}Ga-labeled dimerized-RGD ({sup 68}Ga-RGD{sub 2}). Thirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using {sup 68}Ga-RGD{sub 2}.{sup 18}F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker α{sub v}β{sub 3} in NSCLC and SCLC lesions was analyzed by immunohistochemistry. The {sup 18}F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The {sup 68}Ga-RGD{sub 2} uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of {sup 68}Ga-RGD{sub 2} SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that α{sub v}β{sub 3} integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression. The uptake of {sup 68}Ga-RGD{sub 2} in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower α{sub v}β{sub 3} target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of α{sub v}β{sub 3} also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of α{sub v}β{sub 3} may potentially improve current applications of α{sub v}β{sub 3}-targeted therapy

  16. A search for new mechanisms to inhibit plasmid conjugation

    OpenAIRE

    Getino Redondo, María

    2011-01-01

    Infections due to antibiotic-resistant (AbR) bacteria are a major cause of morbidity and mortality throughout the world. In addition, the number of new antibiotics being developed has plummeted. Although resistance genes can disseminate by any horizontal gene transfer mechanism, the vast majority of reports of bacterial gene transfer in the environment involve conjugation. Our group developed a method for high-throughput analysis of conjugation. This method was used to check for host genes in...

  17. Phase conjugation of gap solitons: A numerical study

    Indian Academy of Sciences (India)

    We study the effect of a nearby phase-conjugate mirror (PCM) on the gap soliton of a Kerr non-linear periodic structure. We show that phase conjugation of the gap soliton (in the sense of replication of the amplitude profile in the reverse direction) is possible under the condition of PCM reflectivity approaching unity. This is in ...

  18. Protein carriers of conjugate vaccines: Characteristics, development, and clinical trials

    OpenAIRE

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characterist...

  19. Synthesis and Antimicrobial Activity of Amino Acids Conjugated Diphenylmethylpiperazine Derivatives

    Directory of Open Access Journals (Sweden)

    K. N. Shivakumara

    2009-01-01

    Full Text Available A series of amino acid conjugated diphenylmethylpiperazine derivatives were synthesized by coupling diphenylmethylpiperazine with different Boc-amino acids using EDCI/HOBt as coupling agent and NMM as base. The synthesized compounds were characterized by 1H-NMR and elemental analysis. The Boc-deblocked derivatives were tested for their antimicrobial activity. We are here reporting that Phe and Trp conjugated diphenylmethylpiperazine showed equally good antibacterial activities as that of conventional antimicrobial drugs.

  20. DNA Interaction Studies of Selected Polyamine Conjugates

    Directory of Open Access Journals (Sweden)

    Marta Szumilak

    2016-09-01

    Full Text Available The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr displacement and DNA unwinding/topoisomerase I/II (Topo I/II activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 × 106 M−1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores.

  1. Conjugated “Molecular Wire” for Excitons

    Energy Technology Data Exchange (ETDEWEB)

    Shibano, Y.; Miller, J.; Imahori, H.; Sreearunothai, P.; Cook, A.R.

    2010-05-06

    We have synthesized new conjugated, rigid rod oligomers of fluorene, F{sub n}(C{sub 60}){sub 2}, n = 4, 8, 12, and 16. These pure compounds have F{sub n} chains up to 140 {angstrom} long. The C{sub 60} groups covalently attached at both ends serve as traps for excitons created in the F{sub n} chains. Excitons created in the chains by photoexcitation reacted rapidly with the C{sub 60} groups with decays described well by the sum of two exponentials. Mean reaction times were 2.3, 5.5, and 10.4 ps for n = 8, 12, and 16. In F{sub 16}(C{sub 60}){sub 2}, the 10.4 ps reaction time was 40 times faster than that found in earlier reports on molecules of slightly longer length. The simplest possible model, that of one-dimensional diffusion of excitonic polarons that react whenever they encounter the end of a chain, fits the results to obtain diffusion coefficients. Deviations of those fits from the data may point to the need for alternative pictures or may just indicate that diffusion is not ideal. The definite lengths of these molecules enable a stringent test for theories. These results reveal that exciton transport can be much faster than previously believed, a finding that could, along with appropriate nanoassembly, enable new kinds of high-efficiency organic photovoltaics.

  2. Charge Transport in Conjugated Block Copolymers

    Science.gov (United States)

    Smith, Brandon; Le, Thinh; Lee, Youngmin; Gomez, Enrique

    Interest in conjugated block copolymers for high performance organic photovoltaic applications has increased considerably in recent years. Polymer/fullerene mixtures for conventional bulk heterojunction devices, such as P3HT:PCBM, are severely limited in control over interfaces and domain length scales. In contrast, microphase separated block copolymers self-assemble to form lamellar morphologies with alternating electron donor and acceptor domains, thereby maximizing electronic coupling and local order at interfaces. Efficiencies as high as 3% have been reported in solar cells for one block copolymer, P3HT-PFTBT, but the details concerning charge transport within copolymers have not been explored. To fill this gap, we probed the transport characteristics with thin-film transistors. Excellent charge mobility values for electron transport have been observed on aluminum source and drain contacts in a bottom gate, bottom contact transistor configuration. Evidence of high mobility in ordered PFTBT phases has also been obtained following thermal annealing. The insights gleaned from our investigation serve as useful guideposts, revealing the significance of the interplay between charge mobility, interfacial order, and optimal domain size in organic block copolymer semiconductors.

  3. Theory of Periodic Conjugate Heat Transfer

    CERN Document Server

    Zudin, Yuri B

    2012-01-01

    This book presents the theory of periodic conjugate heat transfer in a detailed way. The effects of thermophysical properties and geometry of a solid body on the commonly used and experimentally determined heat transfer coefficient are analytically presented from a general point of view. The main objective of the book is a simplified description of the interaction between a solid body and a fluid as a boundary value problem of the heat conduction equation for the solid body. At the body surface, the true heat transfer coefficient is composed of two parts: the true mean value resulting from the solution of the steady state heat transfer problem and a periodically variable part, the periodic time and length to describe the oscillatory hydrodynamic effects. The second edition is extended by (i) the analysis of stability boundaries in helium flow at supercritical conditions in a heated channel with respect to the interaction between a solid body and a fluid; (ii) a periodic model and a method of heat transfer sim...

  4. O:2-CRM(197) conjugates against Salmonella Paratyphi A.

    Science.gov (United States)

    Micoli, Francesca; Rondini, Simona; Gavini, Massimiliano; Lanzilao, Luisa; Medaglini, Donata; Saul, Allan; Martin, Laura B

    2012-01-01

    Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

  5. O:2-CRM(197 conjugates against Salmonella Paratyphi A.

    Directory of Open Access Journals (Sweden)

    Francesca Micoli

    Full Text Available Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2 of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197, using the terminus 3-deoxy-D-manno-octulosonic acid (KDO, thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197 as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

  6. Intense correlation between brain infarction and protein-conjugated acrolein.

    Science.gov (United States)

    Saiki, Ryotaro; Nishimura, Kazuhiro; Ishii, Itsuko; Omura, Tomohiro; Okuyama, Shigeru; Kashiwagi, Keiko; Igarashi, Kazuei

    2009-10-01

    We recently found that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good markers for stroke. The aim of this study was to determine whether the level of protein-conjugated acrolein is increased and levels of spermine and spermidine, the substrates of acrolein production, are decreased at the locus of infarction. A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. The level of protein-conjugated acrolein at the locus of infarction and in plasma was measured by Western blotting and enzyme-linked immunosorbent assay, respectively. The levels of polyamines at the locus of infarction and in plasma were measured by high-performance liquid chromatography. The level of protein-conjugated acrolein was greatly increased, and levels of spermine and spermidine were decreased at the locus of infarction at 24 hours after the induction of stroke. The size of infarction was significantly decreased by N-acetylcysteine, a scavenger of acrolein. It was also found that the increases in the protein-conjugated acrolein, polyamines, and polyamine oxidases in plasma were observed after the induction of stroke. The results indicate that the induction of infarction is well correlated with the increase in protein-conjugated acrolein at the locus of infarction and in plasma.

  7. Cloning and physical characterization of chromosomal conjugative elements in streptococci

    Energy Technology Data Exchange (ETDEWEB)

    Vijayakumar, M.N.; Priebe, S.D.; Pozzi, G.; Hageman, J.M.; Guild, W.R.

    1986-06-01

    A directed insertion method was used to introduce a nonreplicating vector plasmid into the large conjugative cat-tet element found in the chromosome of Streptococcus pneumoniae BM6001 and derivatives. To direct insertion preferentially to the conjugative element, we transferred it by conjugation to Streptococcus faecalis and then used DNA from this strain as a source of restriction nuclease fragments for ligation to digests of the vector pVA891, which can replicate in Escherichia coli but not in streptococci. This ligation mix was used to transform pneumococcal cells carrying the cat-tet element, with selection for the erythromycin resistance carried by pVA891. Eight such isolates were found, and transformation and conjugation tests showed that in each case the vector had inserted into the conjugative element, as expected. DNA from these pneumococcal strains generated a variety of E. coli plasmids which provide tools for obtaining a detailed restriction map and for defining other structural features of the streptococcal conjugative element.

  8. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

    Science.gov (United States)

    Pichichero, Michael E

    2013-12-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.

  9. Comparison of the pharmacological and biological properties of HPMA copolymer-pirarubicin conjugates: A single-chain copolymer conjugate and its biodegradable tandem-diblock copolymer conjugate

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Tsukigawa, K.; Nakamura, H.; Chytil, Petr; Fang, J.; Ulbrich, Karel; Otagiri, M.; Maeda, H.

    2017-01-01

    Roč. 106, 30 August (2017), s. 10-19 ISSN 0928-0987 R&D Projects: GA ČR(CZ) GA15-02986S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:AV ČR,Japan Society for the Promotion of Science(CZ) JSPS-16-05 Program:Bilaterální spolupráce Institutional support: RVO:61389013 Keywords : pirarubicin * PHPMA conjugate * tandem-diblock PHPMA conjugate Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.756, year: 2016

  10. Conjugation effects on antibody-drug conjugates: evaluation of interaction kinetics in real time on living cells.

    Science.gov (United States)

    Bondza, Sina; Stenberg, Jonas; Nestor, Marika; Andersson, Karl; Björkelund, Hanna

    2014-11-03

    Antibody-drug conjugates (ADC) have shown promising effects in cancer therapy by combining the target specificity of an antibody with the toxicity of a chemotherapeutic drug. As the number of therapeutic antibodies is significantly larger than those used as ADCs, there is unused potential for more effective therapies. However, the conjugation of an additional molecule to an antibody may affect the interaction with its target, altering association rate, dissociation rate, or both. Any changes of the binding kinetics can have subsequent effects on the efficacy of the ADCs, thus the kinetics are important to monitor during ADC development and production. This paper describes a method for the analysis of conjugation effects on antibody binding to its antigen, using the instrument LigandTracer and a fluorescent monovalent anti-IgG binder denoted FIBA, which did not affect the interaction. All measurements were done in real time using living cells which naturally expressed the antigens. With this method the binding profiles of different conjugations of the therapeutic anti-EGFR antibody cetuximab and the anti-CD44v6 antibody fragment AbD15171 were evaluated and compared. Even comparatively small modifications of cetuximab altered the interaction with the epidermal growth factor receptor (EGFR). In contrast, no impact on the AbD15171-CD44v6 interaction was observed upon conjugation. This illustrates the importance to study the binding profile for each ADC combination, as it is difficult to draw any general conclusion about conjugation effects. The modification of interaction kinetics through conjugation opens up new possibilities when optimizing an antibody or an ADC, since the conjugations can be used to create a binding profile more apt for a specific clinical need.

  11. Chemical de-conjugation for investigating the stability of small molecule drugs in antibody-drug conjugates.

    Science.gov (United States)

    Chen, Tao; Su, Dian; Gruenhagen, Jason; Gu, Christine; Li, Yi; Yehl, Peter; Chetwyn, Nik P; Medley, Colin D

    2016-01-05

    Antibody-drug conjugates (ADCs) offer new therapeutic options for advanced cancer patients through precision killing with fewer side effects. The stability and efficacy of ADCs are closely related, emphasizing the urgency and importance of gaining a comprehensive understanding of ADC stability. In this work, a chemical de-conjugation approach was developed to investigate the in-situ stability of the small molecule drug while it is conjugated to the antibody. This method involves chemical-mediated release of the small molecule drug from the ADC and subsequent characterization of the released small molecule drug by HPLC. The feasibility of this technique was demonstrated utilizing a model ADC containing a disulfide linker that is sensitive to the reducing environment within cancer cells. Five reducing agents were screened for use in de-conjugation; tris(2-carboxyethyl) phosphine (TCEP) was selected for further optimization due to its high efficiency and clean impurity profile. The optimized de-conjugation assay was shown to have excellent specificity and precision. More importantly, it was shown to be stability indicating, enabling the identification and quantification of the small molecule drug and its degradation products under different formulation pHs and storage temperatures. In summary, the chemical de-conjugation strategy demonstrated here offers a powerful tool to assess the in-situ stability of small molecule drugs on ADCs and the resulting information will shed light on ADC formulation/process development and storage condition selection. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Antagonistic Donor Density Effect Conserved in Multiple Enterococcal Conjugative Plasmids

    Science.gov (United States)

    Bandyopadhyay, Arpan; O'Brien, Sofie; Frank, Kristi L.; Dunny, Gary M.

    2016-01-01

    ABSTRACT Enterococcus faecalis, a common causative agent of hospital-acquired infections, is resistant to many known antibiotics. Its ability to acquire and transfer resistance genes and virulence determinants through conjugative plasmids poses a serious concern for public health. In some cases, induction of transfer of E. faecalis plasmids results from peptide pheromones produced by plasmid-free recipient cells, which are sensed by the plasmid-bearing donor cells. These plasmids generally encode an inhibitory peptide that competes with the pheromone and suppresses self-induction of donors. We recently demonstrated that the inhibitor peptide encoded on plasmid pCF10 is part of a unique quorum-sensing system in which it functions as a “self-sensing signal,” reducing the response to the pheromone in a density-dependent fashion. Based on the similarities between regulatory features controlling conjugation in pAD1 and pAM373 and those controlling conjugation in pCF10, we hypothesized that these plasmids are likely to exhibit similar quorum-sensing behaviors. Experimental findings indicate that for both pAD1 and pAM373, high donor densities indeed resulted in decreased induction of the conjugation operon and reduced conjugation frequencies. This effect was restored by the addition of exogenous inhibitor, confirming that the inhibitor serves as an indicator for donor density. Donor density also affects cross-species conjugative plasmid transfer. Based on our experimental results, we propose models for induction and shutdown of the conjugation operon in pAD1 and pAM373. IMPORTANCE Enterococcus faecalis is a leading cause of hospital-acquired infections. Its ability to transfer antibiotic resistance and virulence determinants by sharing its genetic material with other bacteria through direct cell-cell contact via conjugation poses a serious threat. Two antagonistic signaling peptides control the transfer of plasmids pAD1 and pAM373: a peptide pheromone produced by

  13. Identification of excited states in conjugated polymers

    International Nuclear Information System (INIS)

    Hartwell, Lewis John

    2003-01-01

    This thesis reports quasi steady state photoinduced absorption measurements from three conjugated polymers: polypyridine (PPy), polyfluorene (PFO) and the emeraldine base (EB) form of polyaniline. The aim of these experiments was to determine the nature of the photoexcited states existing in these materials in the millisecond time domain, as this has important consequences for the operation of real devices manufactured using these materials. The results from the photoinduced absorption experiments are closely compared with published results from pulse radiolysis experiments. In all cases there is very good correspondence between the two data sets, which has enabled the photoexcited states to be assigned with a high degree of confidence. Quasi steady-state photoinduced absorption involves the measurement of the change in absorption of a material in response to optical excitation with a laser beam. The changes in absorption are small, so a dedicated instrument was developed and optimised for each different sample. Lock-in techniques were used to recover the small signals from the samples. The samples involved were thin films of the polymer spin coated onto sapphire substrates in the cases of PPy and EB. Solution state experiments were conducted on EB. The experiments on PFO were conducted on aligned and unaligned thin films provided by Sony. In the case of the aligned PFO samples, the photoinduced absorption spectrometer was modified to enable polarisation-sensitive data collection. In PPy, both triplet excitons and polarons have been shown to be long-lived photoexcitations, with photoinduced absorption features at 2.29 eV (triplet exciton transition), 1.5 eV and 0.8 eV (polaron transitions). In PFO, the one observed photoinduced band at 1.52 eV is assigned to a triplet exciton. Two photoinduced absorption bands are observed in EB, at 1.4 eV and 0.8 eV. These are assigned to a self-trapped CT singlet exciton and triplet exciton, respectively. (author)

  14. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    Directory of Open Access Journals (Sweden)

    Alan Perkins

    2002-09-01

    Full Text Available The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C595 (IgG3 which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radioimmunoconjugates of the C595 antibody have been produced with high radiolabelling efficiency and immunoreactivity using Tc-99m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun.A administração de anticorpos conjugados para o tratamento do câncer está agora provando ser de valor clínico. Nós estamos atualmente realizando um programa de estudos clínicos usando o anticorpo monoclonal C595 (IgG3 que reage com a glicoproteína MUC1 que está aberrantemente expressa numa alta proporção de tumores de bexiga. Tem sido produzidos radioimunoconjugados do anticorpo C595, com alta eficiência de radiomarcação e a imunoreatividade, usando-se o Tc-99m e In-111, para o diagnóstico por imagem e estagiamento de doenças. Tem sido produzidos, também, radionuclídeos citotóxicos (Cu-67 e Re-188 para o tratamento de cânceres superficiais de bexiga. A fase terapêutica I/II já se iniciou, envolvendo a administração intravesical do anticorpo diretamente na bexiga.

  15. Conjugated estrogens and breast cancer risk.

    Science.gov (United States)

    Campagnoli, C; Ambroggio, S; Biglia, N; Sismondi, P

    1999-12-01

    Available epidemiologic data suggest the possibility that the use of oral conjugated equine estrogens (CEE) 0.625 mg/day as a first-choice dose could be associated with a very limited (if any) breast cancer risk increase. Some biological peculiarities of oral CEE back the possibility of a limited detrimental effect on breast tissue, due to either direct or indirect actions. Direct actions. Some experimental findings suggest that the 17 alpha-dihydroderivatives of equilenin and equilin (15% of the CEE components) have a non-estrogenic or even an anti-estrogenic effect on breast tissue. This could partially counterbalance the stimulatory action of the other CEE components. Indirect actions. Oral estrogens, through their metabolic and hepatocellular effects (emphasized by the first liver passage) cause a sharp increase in sex hormone binding globulin (SHBG) level which is followed by a lower quantity of both estrogen and androgen in the free, bioavailable, form. More importantly, they cause a decrease in circulating insulin-like growth factor I (IGF-I) activity, due to both a reduction in IGF-I synthesis by the liver and an increase in IGF-binding protein-1 level. A strong relationship between breast cancer risk and the concentration of circulating IGF-I in premenopausal women has been recently found. Actually, estrogens and IGF-I have a synergistic effect on cell proliferation, and IGF-I is necessary for maximum estrogen-receptor activation in breast cancer cell lines. The possibility does exist that the SHBG level increase and the IGF-I bioavailability decrease, caused by oral CEE, balance the increased estrogen stimulation on breast tissue.

  16. Recent Advances in Conjugated Polymers for Light Emitting Devices

    Science.gov (United States)

    AlSalhi, Mohamad Saleh; Alam, Javed; Dass, Lawrence Arockiasamy; Raja, Mohan

    2011-01-01

    A recent advance in the field of light emitting polymers has been the discovery of electroluminescent conjugated polymers, that is, kind of fluorescent polymers that emit light when excited by the flow of an electric current. These new generation fluorescent materials may now challenge the domination by inorganic semiconductor materials of the commercial market in light-emitting devices such as light-emitting diodes (LED) and polymer laser devices. This review provides information on unique properties of conjugated polymers and how they have been optimized to generate these properties. The review is organized in three sections focusing on the major advances in light emitting materials, recent literature survey and understanding the desirable properties as well as modern solid state lighting and displays. Recently, developed conjugated polymers are also functioning as roll-up displays for computers and mobile phones, flexible solar panels for power portable equipment as well as organic light emitting diodes in displays, in which television screens, luminous traffic, information signs, and light-emitting wallpaper in homes are also expected to broaden the use of conjugated polymers as light emitting polymers. The purpose of this review paper is to examine conjugated polymers in light emitting diodes (LEDs) in addition to organic solid state laser. Furthermore, since conjugated polymers have been approved as light-emitting organic materials similar to inorganic semiconductors, it is clear to motivate these organic light-emitting devices (OLEDs) and organic lasers for modern lighting in terms of energy saving ability. In addition, future aspects of conjugated polymers in LEDs were also highlighted in this review. PMID:21673938

  17. Understanding conjugation and hyperconjugation from electronic delocalization measures.

    Science.gov (United States)

    Feixas, Ferran; Matito, Eduard; Poater, Jordi; Solà, Miquel

    2011-11-17

    The concepts of conjugation and hyperconjugation play an important role to provide an explanation for several fundamental phenomena observed in organic chemistry. Because these effects cannot be directly measured experimentally, their assessment became a primary concern for chemists from the very beginning. In general, the stabilization produced by both phenomena has been studied by means of isodesmic reactions and energy based analysis such as the energy decomposition analysis. In recent years, electronic delocalization measures have been successfully applied to elucidate the nature of chemical bonding and the aromatic character of all kind of molecules. Because conjugation and hyperconjugation stabilizations are strongly linked to the concept of electron delocalization, this paper will give an account of both effects from the point of view of electronic delocalization measures calculated within the framework of the quantum theory of atoms in molecules. In particular, we focus our attention in the controversial case of the stabilization by conjugation in 1,3-butadiyne and 1,3-butadiene. Unexpectedly, theoretical calculations based on the scheme proposed by Kistiakowsky to quantify the extent of stabilization due to conjugation predicted that the conjugation of 1,3-butadiyne was zero. Subsequent energetic analyses contradicted this observation. These studies pointed out the presence of hyperconjugation stabilization in the hydrogenated product of 1,3-butadiyne and 1,3-butadiene that were used as reference systems in the Kistiakowsky's scheme. Consequently, the extra stabilization of 1-butyne due to hyperconjugation hides the stabilization by conjugation of 1,3-butadiyne. Our results based on electron delocalization measures confirm both the presence of conjugation in 1,3-butadiene and 1,3-butadiyne and hyperconjugation stabilization in their respective hydrogenated products, 1-butene and 1-butyne.

  18. Optical observations geomagnetically conjugate to sprite-producing lightning discharges

    Directory of Open Access Journals (Sweden)

    R. A. Marshall

    2005-09-01

    Full Text Available Theoretical studies have predicted that large positive cloud-to-ground discharges can trigger a runaway avalanche process of relativistic electrons, forming a geomagnetically trapped electron beam. The beam may undergo pitch angle and energy scattering during its traverse of the Earth's magnetosphere, with a small percentage of electrons remaining in the loss cone and precipitating in the magnetically conjugate atmosphere. In particular, N2 1P and N2+1N optical emissions are expected to be observable. In July and August 2003, an attempt was made to detect these optical emissions, called "conjugate sprites", in correlation with sprite observations in Europe near . Sprite observations were made from the Observatoire du Pic du Midi (OMP in the French Pyrenées, and VLF receivers were installed in Europe to detect causative sferics and ionospheric disturbances associated with sprites. In the Southern Hemisphere conjugate region, the Wide-angle Array for Sprite Photometry (WASP was deployed at the South African Astronomical Observatory (SAAO, near Sutherland, South Africa, to observe optical emissions with a field-of-view magnetically conjugate to the Northern Hemisphere observing region. Observations at OMP revealed over 130 documented sprites, with WASP observations covering the conjugate region successfully for 30 of these events. However, no incidences of optical emissions in the conjugate hemisphere were found. Analysis of the conjugate optical data from SAAO, along with ELF energy measurements from Palmer Station, Antarctica, and charge-moment analysis, show that the lightning events during the course of this experiment likely had insufficient intensity to create a relativistic beam. Keywords. Ionosphere (Ionsophere-magnetosphere interactions; Ionospheric disturbances; Instruments and techniques

  19. New heparin–indomethacin conjugate with an ester linkage: Synthesis, self aggregation and drug delivery behavior

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nan-Nan; Zheng, Bing-Na [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Lin, Jian-Tao [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Medical College, Dongguan 523808 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)

    2014-01-01

    New heparin–indomethacin conjugate with an ester linkage was prepared by the carbodiimide-mediated condensation reaction, and then characterized by FTIR and {sup 1}HNMR analyses. Due to its amphiphilic character, such a conjugate could self-aggregate into spherical nanoparticles in aqueous system, as confirmed by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. By the in vitro drug release tests, the resultant conjugate nanoparticles were found to have a sustained and esterase-sensitive release behavior for conjugated indomethacin. In addition, the uptake of these conjugate nanoparticles into human nasopharyngeal carcinoma CNE1 cells was confirmed by fluorescence microscopy. - Highlights: • New heparin–indomethacin conjugate with an ester linkage was prepared. • Such a conjugate could self-aggregate into spherical nanoparticles in aqueous system. • The resultant conjugate nanoparticles exhibited an esterase-sensitive drug release behavior. • The resultant conjugate nanoparticles showed the cellular uptake ability in CNE1 cells.

  20. Simple and Efficient Method to Purify DNA–Protein Conjugates and Its Sensing Applications

    Science.gov (United States)

    2015-01-01

    DNA–protein conjugates are very useful in analytical chemistry for target recognition and signal amplification. While a number of methods for conjugating DNA with proteins are known, methods for purification of DNA–protein conjugates from reaction mixture containing unreacted proteins are much less investigated. In this work, a simple and efficient approach to purify DNA–invertase conjugates from reaction mixture via a biotin displacement strategy to release desthiobiotinylated DNA–invertase conjugates from streptavidin-coated magnetic beads was developed. The conjugates purified by this approach were utilized for quantitative detection of cocaine and DNA using a personal glucose meter through structure-switching DNA aptamer sensors and competitive DNA hybridization assays, respectively. In both cases, the purified DNA–invertase conjugates showed better performance compared to the same assays using unpurified conjugates. The approach demonstrated here can be further expanded to other DNA and proteins to generate purified DNA–protein conjugates for analytical and other applications. PMID:24605905

  1. Conjugate Haemophilus influenzae type b vaccines for sickle cell disease.

    Science.gov (United States)

    Allali, Slimane; Chalumeau, Martin; Launay, Odile; Ballas, Samir K; de Montalembert, Mariane

    2016-02-16

    People affected with sickle cell disease are at high risk of infection from Haemophilus influenzae type b. Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Haemophilus influenzae type b remains one of the most common cause of bacteraemias in children with sickle cell disease. The increased uptake of this conjugate vaccination may substantially improve the survival of children with sickle cell disease. The primary objective was to determine whether Haemophilus influenzae type b conjugate vaccines reduce mortality and morbidity in children and adults with sickle cell disease.The secondary objectives were to assess the following in children and adults with sickle cell disease: the immunogenicity of Haemophilus influenzae type b conjugate vaccines; the safety of these vaccines; and any variation in effect according to type of vaccine, mode of administration (separately or in combination with other vaccines), number of doses, and age at first dose. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also contacted relevant pharmaceutical companies to identify unpublished trials.Date of last search: 23 November 2015. All randomised and quasi-randomised controlled trials comparing Haemophilus influenzae type b conjugate vaccines with placebo or no treatment, or comparing different types of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease. No trials of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease were found. There is an absence of evidence from randomised controlled trials relating to the subject of this review. There has

  2. Sub-inhibitory concentrations of fluoroquinolones increase conjugation frequency.

    Science.gov (United States)

    Shun-Mei, E; Zeng, Jian-Ming; Yuan, Hui; Lu, Yang; Cai, Ren-Xin; Chen, Cha

    2018-01-01

    Bacteria are subjected to sub-minimal inhibitory concentrations (sub-MIC) of antibiotics in various niches where the low-dosage treatment plays a key role in antibiotic resistance selection. However, the mechanism of sub-MIC of antibiotics on the resistant gene transfer is largely unknown. Here, we used Escherichia coli SM10λpir in which the RP4 plasmid was chromosomally-integrated as the donor strain, to investigate the effects of sub-MIC of Ciprofloxacin(Cip) or Levofloxacin(Lev) on conjugational transfer of mobilisable plasmid-pUCP24T from SM10λpir to Pseudomonas aeruginosa. The results showed that the transfer frequency was significantly increased by treating E. coli with sub-MIC of Cip or Lev. To investigate the molecular mechanisms, complete transcriptome sequencing was performed. We found that the sub-MIC of Cip or Lev enhanced the expression of several genes on the RP4 plasmid, which was consistent with the conjugation efficiency. Moreover, the expression of genes associated with SOS response in donor SM10λpir was increased, but had no correlation with conjugation efficiency. These findings suggested that sub-MIC of Cip or Lev may promote conjugational transfer by up-regulating the expression of conjugation associated genes via an SOS-independent mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Social behavior and decision making in bacterial conjugation.

    Science.gov (United States)

    Koraimann, Günther; Wagner, Maria A

    2014-01-01

    Bacteria frequently acquire novel genes by horizontal gene transfer (HGT). HGT through the process of bacterial conjugation is highly efficient and depends on the presence of conjugative plasmids (CPs) or integrated conjugative elements (ICEs) that provide the necessary genes for DNA transmission. This review focuses on recent advancements in our understanding of ssDNA transfer systems and regulatory networks ensuring timely and spatially controlled DNA transfer (tra) gene expression. As will become obvious by comparing different systems, by default, tra genes are shut off in cells in which conjugative elements are present. Only when conditions are optimal, donor cells-through epigenetic alleviation of negatively acting roadblocks and direct stimulation of DNA transfer genes-become transfer competent. These transfer competent cells have developmentally transformed into specialized cells capable of secreting ssDNA via a T4S (type IV secretion) complex directly into recipient cells. Intriguingly, even under optimal conditions, only a fraction of the population undergoes this transition, a finding that indicates specialization and cooperative, social behavior. Thereby, at the population level, the metabolic burden and other negative consequences of tra gene expression are greatly reduced without compromising the ability to horizontally transfer genes to novel bacterial hosts. This undoubtedly intelligent strategy may explain why conjugative elements-CPs and ICEs-have been successfully kept in and evolved with bacteria to constitute a major driving force of bacterial evolution.

  4. Chitosan conjugation enables intracellular bacteria susceptible to aminoglycoside antibiotic.

    Science.gov (United States)

    Mu, Haibo; Niu, Hong; Wang, Dongdong; Sun, Feifei; Sun, Yuelin; Duan, Jinyou

    2016-11-01

    Most chronic infections are difficult to eradicate because bacteria capable of surviving in host-infected cells may be protected from the killing actions of antibiotics, leading to therapy failures and disease relapses. Here we demonstrated that covalent-coupling chitosan to streptomycin significantly improved intracellular bactericidal capacity towards multiple organisms within phagocytic or nonphagocytic cells. Structure-activity relationship investigations indicated that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this intracellular bactericidal activity. Mechanistic insight demonstrated the conjugate was capable to target and eliminate endocytic or endosomal escaped bacteria through facilitating the direct contact between the antibiotic and intracellular organism. In vivo acute infection models indicated that compared to equal dose of the antibiotic, chitosan-streptomycin (C-S) conjugate and especially the human serum album binding chitosan-streptomycin conjugate (HCS) complex formed by human serum album and C-S conjugate greatly decreased the bacteria burden in the spleen and liver in both wild type and immuno-suppressive mice. Furthermore, the HCS complex remarkably reduced mortality of infected TLR2 deficient mice, mimicking immune-compromised persons who were more susceptible to bacterial infections. These findings might open up a new avenue to combat intracellular bacterial infection by aminoglycosides antibiotics at a lower effective dose. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Free and conjugated dopamine in human ventricular fluid

    International Nuclear Information System (INIS)

    Sharpless, N.S.; Thal, L.J.; Wolfson, L.I.; Tabaddor, K.; Tyce, G.M.; Waltz, J.M.

    1981-01-01

    Free dopamine and an acid hydrolyzable conjugate of dopamine were measured in human ventricular fluid specimens with a radioenzymatic assay and by high performance liquid chromatography (HPLC) with electrochemical detection. Only trace amounts of free norepinephrine and dopamine were detected in ventricular fluid from patients with movement disorders. When the ventricular fluid was hydrolyzed by heating in HClO 4 or by lyophilization in dilute HClO 4 , however, a substantial amount of free dopamine was released. Values for free plus conjugated dopamine in ventricular fluid from patients who had never taken L-DOPA ranged from 139 to 340 pg/ml when determined by HPLC and from 223 to 428 pg/ml when measured radioenzymatically. The correlation coefficient for values obtained by the two methods in the same sample of CSF was 0.94 (P<0.001). Patients who had been treated with L-DOPA had higher levels of conjugated dopamine in their ventricular CSF which correlated inversely with the time between the last dose of L-DOPA and withdrawal of the ventricular fluid. Additionally, one patient with acute cerebral trauma had elevated levels of free norepinephrine and both free and conjugated dopamine in his ventricular fluid. Conjugation may be an important inactivation pathway for released dopamine in man. (Auth.)

  6. Conjugated Linoleic Triacylglycerols Exhibit Superior Lymphatic Absorption Than Free Conjugate Linoleic Acids and Have Antiobesity Properties.

    Science.gov (United States)

    Woo, Hyunjoon; Chung, Min-Yu; Kim, Juyeon; Kong, Daecheol; Min, Jinyoung; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2016-05-01

    This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity.

  7. Preparation and characterization of a hetero functional system of gold nanoparticles labeled with {sup 99m}Tc and conjugated to the sequence Arg-Gly-Asp for detection in vivo of angio genesis and evaluation of their toxicity in Hyalella aztec; Preparacion y caracterizacion de un sistema heterofuncional de nanoparticulas de oro marcadas con Tecnecio-99m y conjugadas a la secuencia Arg-Gly-Asp para la deteccion in vivo de angiogenesis y la evaluacion de su toxicidad en Hyalella azteca

    Energy Technology Data Exchange (ETDEWEB)

    Morales A, E.

    2012-07-01

    Integrin s play critical roles in many physiological processes including angio genesis and also contribute to pathological events such as tumor invasion and metastasis. The {alpha}{sub v}{beta}{sub 3} integrin is expressed in normal endothelial cells but it is over-expressed in the tumor neo vasculature. Peptides based on the Arginine-Glycine-Aspartic acid (RGD) sequence have been reported as molecules with high affinity and selectivity for the {alpha}{sub v}{beta}{sub 3} integrin. Recent studies have demonstrated that conjugating peptides to gold nanoparticles (AuNP) produces biocompatible and stable multifunctional systems with target-specific molecular recognition due to multivalent effects produced by multiple simultaneous interactions between peptides and their receptors. The first aim of this research was to prepare a m ultimeric system of {sup 99m}Tc labeled gold particles conjugated to c[RGDfK(C)] and to evaluate its biological behavior as a potential radiopharmaceutical for molecular imaging of {alpha}{sub v}{beta}{sub 3} tumor expression. Hidrazinonicotinamide-G GC (HYNIC-G GC) and C[RGDfK(C)] peptides were synthesized and conjugated to AuNP (20 nm) by means of spontaneous reaction of the thiol groups of cysteine. The nano conjugate was characterized by transmission electron microscopy, Fourier transform-infrared, Ultraviolet-vis, X-ray photoelectron spectroscopy and Raman spectroscopy. To obtain {sup 99m}Tc-HYNIC-G GC-AuNP-c[RGDfK(C)], the {sup 99m}Tc-HYNIC-G GC radio peptide was first prepared and added to the AuNP solution followed by c[RGDfK(C)]. Radiochemical purity (Rp) was determined by size-exclusion HPLC and I TLC-Sg analyses. In vitro binding studies were carried out in {alpha}{sub v}{beta}{sub 3} receptor-positive C6 glioma cancer cells. Biodistribution studies were accomplished in athymic mice with C6-induced tumors with blocked and non blocked receptors, and images were obtained using a micro-SPECT/CT. Transmission electron microscopy and

  8. Repercussions of imprisonment for conjugal violence: discourses of men

    Directory of Open Access Journals (Sweden)

    Anderson Reis de Sousa

    Full Text Available ABSTRACT Objective: to know the consequences that men experience related to incarceration by conjugal violence. Methods: qualitative study on 20 men in jail and indicted in criminal processes related to conjugal violence in a Court specialized in Family and Domestic Violence against women. The interviews were classified based on Collective Subject Discourse method, using NVIVO(r software. Results: the collective discourse shows that the experience of preventive imprisonment starts a process of family dismantling, social stigma, financial hardship and psycho-emotional symptoms such as phobia, depression, hypertension, and headaches. Conclusion: due to the physical, mental and social consequences of the conjugal violence-related imprisonment experience, it is urgent to look carefully into the somatization process as well as to the prevention strategies regarding this process.

  9. Collision bottleneck throughput in bacterial conjugation-based nanonetworks.

    Science.gov (United States)

    Islam, Nabiul; Misra, Sudip

    2015-01-01

    Bacterial conjugation-based nanonetwork has been recently proposed as a novel molecular communication paradigm, in which the bacteria act as carriers. This is the foundational work proposing the phenomenon of collision which occurs in the form of multi-conjugation of multiple carrier bacteria at the side of receiver nanodevice. We show the effect of this conjugation-based collision on the maximum achievable throughput of the network, using a simple graph-theoretic approach, namely, Maximum Weight Bipartite Matching. One of the several interesting results that emerges concerns the maximum achievable throughput, which is bounded by Θ(n/p) in case of homogeneous nodes, where n and p refer to the total number of nodes, and the vertical layers in the network, respectively.

  10. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  11. Topologically Directed Assemblies of Semiconducting Sphere-Rod Conjugates.

    Science.gov (United States)

    Lin, Zhiwei; Yang, Xing; Xu, Hui; Sakurai, Tsuneaki; Matsuda, Wakana; Seki, Shu; Zhou, Yangbin; Sun, Jian; Wu, Kuan-Yi; Yan, Xiao-Yun; Zhang, Ruimeng; Huang, Mingjun; Mao, Jialin; Wesdemiotis, Chrys; Aida, Takuzo; Zhang, Wei; Cheng, Stephen Z D

    2017-12-27

    Spontaneous organizations of designed elements with explicit shape and symmetry are essential for developing useful structures and materials. We report the topologically directed assemblies of four categories (a total of 24) of sphere-rod conjugates, composed of a sphere-like fullerene (C 60 ) derivative and a rod-like oligofluorene(s) (OF), both of which are promising organic semiconductor materials. Although the packing of either spheres or rods has been well-studied, conjugates having both shapes substantially enrich resultant assembled structures. Mandated by their shapes and topologies, directed assemblies of these conjugates result not only in diverse unconventional semiconducting supramolecular lattices with controlled domain sizes but also in tunable charge transport properties of the resulting structures. These results demonstrate the importance of persistent molecular topology on hierarchically assembled structures and their final properties.

  12. Progress towards meningitis prevention in the conjugate vaccines era

    Directory of Open Access Journals (Sweden)

    Cristina Aparecida Borges Laval

    Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

  13. Small angle scattering from protein/sugar conjugates

    Science.gov (United States)

    Jackson, Andrew; White, John

    2006-11-01

    The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5 mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75 A˚ for beta casein in solution and around 80 A˚ for the sucrose conjugate.

  14. Small angle scattering from protein/sugar conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Andrew [Research School of Chemistry, Australian National University, Canberra, ACT 0200 (Australia)]. E-mail: ajj@nist.gov; White, John [Research School of Chemistry, Australian National University, Canberra, ACT 0200 (Australia)

    2006-11-15

    The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75A-bar for beta casein in solution and around 80A-bar for the sucrose conjugate.

  15. Small angle scattering from protein/sugar conjugates

    International Nuclear Information System (INIS)

    Jackson, Andrew; White, John

    2006-01-01

    The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75A-bar for beta casein in solution and around 80A-bar for the sucrose conjugate

  16. Scintillation Reduction using Conjugate-Plane Imaging (Abstract)

    Science.gov (United States)

    Vander Haagen, G. A.

    2017-12-01

    (Abstract only) All observatories are plagued by atmospheric turbulence exhibited as star scintillation or "twinkle" whether a high altitude adaptive optics research or a 30-cm amateur telescope. It is well known that these disturbances are caused by wind and temperature-driven refractive gradients in the atmosphere and limit the ultimate photometric resolution of land-based facilities. One approach identified by Fuchs (1998) for scintillation noise reduction was to create a conjugate image space at the telescope and focus on the dominant conjugate turbulent layer within that space. When focused on the turbulent layer little or no scintillation exists. This technique is described whereby noise reductions of 6 to 11/1 have been experienced with mathematical and optical bench simulations. Discussed is a proof-of-principle conjugate optical train design for an 80-mm, f7 telescope.

  17. The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

    Science.gov (United States)

    Poulin-Laprade, Dominic; Carraro, Nicolas; Burrus, Vincent

    2015-01-01

    Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

  18. Effect of extended π-conjugation structure of donor-acceptor conjugated copolymers on the photoelectronic properties.

    Science.gov (United States)

    Wang, Meng; Shi, Shaowei; Ma, Di; Shi, Keli; Gao, Chen; Wang, Liwei; Yu, Gui; Li, Yongfang; Li, Xiaoyu; Wang, Haiqiao

    2014-10-01

    New donor-acceptor conjugated copolymers based on alkylthienylbenzodithiophene (BDTT) and alkoxynaphthodithiophene (NDT) have been synthesized and compared with their benzo[1,2-b:4,5-b']dithiophene (BDT)-based analogues to investigate the effect of the extended π conjugation of the polymer main chain on the physicochemical properties of the polymers. A systematic investigation into the optical properties, energy levels, field-effect transistor characteristics, and photovoltaic characteristics of these polymers was conducted. Both polymers demonstrated enhanced photovoltaic performance and increased hole mobility compared with the BDT-based analogue. However, the BDTT-based polymer (with π-conjugation extension perpendicular to main chain) gave the highest power conversion efficiency of 5.07% for the single-junction polymer solar cell, whereas the NDT-based polymer (with π-conjugation extension along the main chain) achieved the highest hole mobility of approximately 0.1 cm(2) V(-1)  s(-1) based on the field-effect transistor; this indicated that extending the π conjugation in different orientations would have a significant influence on the properties of the resulting polymers. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Conical Emissions and Phase Conjugation in Atomic Sodium

    Science.gov (United States)

    Pender, John George

    This thesis is concerned with degenerate phase conjugation in atomic sodium vapor. The theory and experiment of this process are examined on three different levels. Each level explores the interactions in greater detail that the last in order to model experimental observations of ever increasing complexity. The thesis begins with an application of existing theory. The phase conjugate beam is produced by the interaction of a probe and a pair of counterpropagating pumps. The strength of the phase conjugate beam depends on the sodium density in the interaction volume. The goal is to study this relationship in detail so that phase conjugation may be developed as a nonintrusive optical combustion diagnostic. Phase conjugation is explored in greater detail when it becomes apparent through experiment that previous theory fails to model the process when the angle between the probe and the pump axis is small. The analysis is extended to include self-induced refractive index changes and higher-order coupling terms for both a single pump and for a pair of counterpropagating pumps. It is shown for each case that phasematching can occur for probe angles near 1 degree. The thesis concludes with the examination of a series of novel phenomena which occur when a single laser pump or a pair of counterpropagating pumps is passed through a small, high density sodium-seeded flame. These phenomena take the form of a hollow conical surface concentric with each pump as it exists the flame. No external probe is introduced. The analysis developed here for phase conjugation is generalized to accommodate a large number of weak probes. In this way the cones are modeled via the interaction of the pump(s) and elastically scattered laser light. It is shown that the laser-pumped flame is an optical resonator whose fundamental mode structure consists of a hollow conical surface.

  20. Investigations of conjugate MSTIDS over the Brazilian sector during daytime

    Science.gov (United States)

    Jonah, O. F.; Kherani, E. A.; De Paula, E. R.

    2017-09-01

    This study focuses on the daytime medium-scale traveling ionospheric disturbances (MSTIDs) observed at conjugate hemispheres. It is the first time that the geomagnetical conjugate daytime MSTIDs are observed over the South America sector. To observe the MSTID characteristics, we used detrended total electron content (TEC) derived from Global Navigation Satellite Systems receivers located at Brazilian sector covering the Northern and Southern Hemispheres along the same magnetic meridian. The geographic grid of 1°N to 14°S in latitude and 60°S to 50°S in longitude was selected for this study. The cross-correlation method between two latitudes and longitudes in time was used to observe the propagation of the MSTID waves. The following features are noted: (a) MSTIDs are well developed at both hemispheres; (b) the peak MSTIDs amplitudes vary from one hemisphere to another; hence, we suppose that MSTIDs generated in Southern Hemisphere or Northern Hemisphere mirrored in the conjugate hemisphere; (c) the gravity wave-induced electric fields from one hemisphere map along the field lines and generate the mirrored MSTIDs in the conjugate region. To investigate the hemispheric mapping mechanism, a rough approximation for the integrated field line conductivity ratio of E and F regions is calculated using digisonde E and F region parameters. We noted that during the period of mapping the decrease in E region conductivity results in an increase in total conductivity. This shows that the E region was partially short circuited; hence, electric field generated at F region could map to the conjugate hemisphere during daytime: daytime MSTIDs at conjugate regions; mechanisms responsible for daytime electrified MSTIDs; gravity wave-induced electric field role in daytime MSTIDs.

  1. Double phase-conjugate mirror: analysis, demonstration, and applications.

    Science.gov (United States)

    Weiss, S; Sternklar, S; Fischer, B

    1987-02-01

    We report on the operation of the double phase-conjugate mirror (DPCM). Two inputs to opposite sides of a photorefractive barium titanate crystal, which may carry different spatial images, are shown to pump the same four-wave mixing process mutually and are self-refracted without any external or internal crystal surface. This results in the phase-conjugate reproduction of the two images simultaneously. This device is analyzed theoretically, and applications in image processing, interferometry, and rotation sensing are discussed. We also demonstrate the operation of a ring laser, using the DPCM, as well as a photorefractive resonator with two facing DPCM's that can support spatial information in its oscillations.

  2. Conjugate heat and mass transfer in heat mass exchanger ducts

    CERN Document Server

    Zhang, Li-Zhi

    2013-01-01

    Conjugate Heat and Mass Transfer in Heat Mass Exchanger Ducts bridges the gap between fundamentals and recent discoveries, making it a valuable tool for anyone looking to expand their knowledge of heat exchangers. The first book on the market to cover conjugate heat and mass transfer in heat exchangers, author Li-Zhi Zhang goes beyond the basics to cover recent advancements in equipment for energy use and environmental control (such as heat and moisture recovery ventilators, hollow fiber membrane modules for humidification/dehumidification, membrane modules for air purification, desi

  3. Imaging GABAc Receptors with Ligand-Conjugated Quantum Dots

    Directory of Open Access Journals (Sweden)

    Ian D. Tomlinson

    2007-01-01

    Full Text Available We report a methodology for labeling the GABAc receptor on the surface membrane of intact cells. This work builds upon our earlier work with serotonin-conjugated quantum dots and our studies with PEGylated quantum dots to reduce nonspecific binding. In the current approach, a PEGylated derivative of muscimol was synthesized and attached via an amide linkage to quantum dots coated in an amphiphilic polymer derivative of a modified polyacrylamide. These conjugates were used to image GABAC receptors heterologously expressed in Xenopus laevis oocytes.

  4. Poly(trimethylsilylcyclooctatetraene): A soluble conjugated polyacetylene via olefin metathesis

    Energy Technology Data Exchange (ETDEWEB)

    Ginsburg, E.J.; Gorman, C.B.; Grubbs, R.H.; Marder, S.R. (California Institute of Technology, Pasadena (USA))

    1989-09-13

    highly conjugated polymers, such as polyacetylene, polythiophene, and poly(p-phenylene vinylene), have been the subject of intensive research due to their intriguing optical and electronic properties. These parent systems are highly desirable for experimental and theoretical studies due to their simplicity. Their intractability, however, has made characterization an arduous task, and insolubility has severely limited their applications. Researchers have successfully circumvented these obstacles by synthesizing soluble alkyl- and alkoxy-substituted polythiphenes and poly(p-phenylene vinylenes). Analogous soluble highly conjugated polyacetylene derivatives have proven more elusive. The authors report here the synthesis of such a polymer using ring-opening metathesis polymerization (ROMP).

  5. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

    . Subsequently, the immunomodulating substance is also bound in a chemoselective manner, to give a dendrimer conjugate with a well-defined structure and connectivity and containing a precise, pre-determined ratio of carbohydrate to immunomodulating substance. The invention also relates to novel dendrimer......A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner...

  6. Peptide π-Electron Conjugates: Organic Electronics for Biology?

    Science.gov (United States)

    Ardoña, Herdeline Ann M; Tovar, John D

    2015-12-16

    Highly ordered arrays of π-conjugated molecules are often viewed as a prerequisite for effective charge-transporting materials. Studies involving these materials have traditionally focused on organic electronic devices, with more recent emphasis on biological systems. In order to facilitate the transition to biological environments, biomolecules that can promote hierarchical ordering and water solubility are often covalently appended to the π-electron unit. This review highlights recent work on π-conjugated systems bound to peptide moieties that exhibit self-assembly and aims to provide an overview on the development and emerging applications of peptide-based supramolecular π-electron systems.

  7. Conjugate gradient heat bath for ill-conditioned actions.

    Science.gov (United States)

    Ceriotti, Michele; Bussi, Giovanni; Parrinello, Michele

    2007-08-01

    We present a method for performing sampling from a Boltzmann distribution of an ill-conditioned quadratic action. This method is based on heat-bath thermalization along a set of conjugate directions, generated via a conjugate-gradient procedure. The resulting scheme outperforms local updates for matrices with very high condition number, since it avoids the slowing down of modes with lower eigenvalue, and has some advantages over the global heat-bath approach, compared to which it is more stable and allows for more freedom in devising case-specific optimizations.

  8. Toward High Performance Photovoltaic Cells based on Conjugated Polymers

    Science.gov (United States)

    2016-12-26

    AFRL-AFOSR-JP-TR-2016-0103 Toward High Performance Photovoltaic Cells based on Conjugated Polymers Kung-Hwa Wei National Chiao Tung University Final...Conjugated Polymers 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386-15-1-4113 5c.  PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) Kung-Hwa Wei 5d.  PROJECT...gap polymer with good packing order as the active layer for a single-junction photovoltaic device. The light absorptions for the small molecule and the

  9. Side Chain Engineering in Solution-Processable Conjugated Polymers

    KAUST Repository

    Mei, Jianguo

    2014-01-14

    Side chains in conjugated polymers have been primarily utilized as solubilizing groups. However, these side chains have roles that are far beyond. We advocate using side chain engineering to tune a polymer\\'s physical properties, including absorption, emission, energy level, molecular packing, and charge transport. To date, numerous flexible substituents suitable for constructing side chains have been reported. In this Perspective article, we advocate that the side chain engineering approach can advance better designs for next-generation conjugated polymers. © 2013 American Chemical Society.

  10. A feasible DY conjugate gradient method for linear equality constraints

    Science.gov (United States)

    LI, Can

    2017-09-01

    In this paper, we propose a feasible conjugate gradient method for solving linear equality constrained optimization problem. The method is an extension of the Dai-Yuan conjugate gradient method proposed by Dai and Yuan to linear equality constrained optimization problem. It can be applied to solve large linear equality constrained problem due to lower storage requirement. An attractive property of the method is that the generated direction is always feasible and descent direction. Under mild conditions, the global convergence of the proposed method with exact line search is established. Numerical experiments are also given which show the efficiency of the method.

  11. Electronic states of emodin and its conjugate base

    DEFF Research Database (Denmark)

    Nguyen, Son Chi; Hansen, Bjarke Knud Vilster; Hoffmann, Søren Vrønning

    2008-01-01

    The electronic transitions of emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, E) and its conjugate base (3-oxido-6-methyl-1,8-dihydroxy-9,10-anthraquinone, Ecb) were investigated by UV-Vis linear dichroism (LD) spectroscopy on molecular samples aligned in stretched poly(vinylalcohol). The e......The electronic transitions of emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, E) and its conjugate base (3-oxido-6-methyl-1,8-dihydroxy-9,10-anthraquinone, Ecb) were investigated by UV-Vis linear dichroism (LD) spectroscopy on molecular samples aligned in stretched poly...

  12. Trilhando caminhos para o enfrentamento da violência conjugal

    OpenAIRE

    Gomes, Nadirlene Pereira

    2009-01-01

    179f. Pelo seu caráter multifacetado, a violência conjugal consiste em um problema social, político, econômico e de saúde que requer a interdisciplinaridade e a intersetorialidade para sua compreensão e seu enfrentamento. Estudo exploratório, descritivo, com utilização de multimétodos, envolvendo aspectos quantitativos e qualitativos, fundamentado na Teoria das Representações Sociais. O objeto de estudo consiste no processo de enfrentamento da violência conjugal. Objetivou-se analisar o pr...

  13. Highly Potent Antibacterial Organometallic Peptide Conjugates.

    Science.gov (United States)

    Albada, Bauke; Metzler-Nolte, Nils

    2017-10-17

    Resistance of pathogenic bacteria against currently marketed antibiotics is again increasing. To meet the societal need for effective cures, scientists are faced with the challenge of developing more potent but equally bacteria-specific drugs. Currently, most efforts are directed toward the modification of existing antibiotics, but ideally, compounds with a new mode of action are required. In this Account, we detail our findings in the area of novel metal-based antibiotics. Our strategy is based on the modification of simple antimicrobial peptides (AMPs) with organometallic agents, resulting in organometallic AMPs (OM-AMPs). Since bacteria have most likely never encountered these synthetically prepared unnatural organometallic agents, we anticipated that such agents could well become potentiating players in the antibiotics arena. Moreover, exploiting some of the particular properties of metal complexes should also help to elucidate the mode of action of small cationic AMPs, the molecular details of which have remained elusive despite intensive efforts. Using standard Fmoc/tBu-based solid-phase peptide synthesis approaches, we have prepared various organometallic-peptide conjugates with covalently linked group 8 and 9 metallocenes (ferrocene, ruthenocene, osmocene, and cobaltocenium). As a starting point we took the (RW) 3 antibacterial hexapeptide lead structure. After modifying the peptide sequence (generations 1 and 2), changing the nature and position of the organometallic group (generation 3), and optimizing the amino acid chirality (generation 5), we identified several organometallic antibacterial peptides that are currently among the most active synthetic AMPs (synAMPs) that have ever been prepared. Through these rational and systematic optimizations, we were able to increase the antibacterial activity of a short non-organometallic synAMP 18-fold to submicromolar activity, rivaling the activity of vancomycin (often the drug of last resort) against methicillin

  14. Light-emitting conjugated polymers with microporous network architecture: interweaving scaffold promotes electronic conjugation, facilitates exciton migration, and improves luminescence.

    Science.gov (United States)

    Xu, Yanhong; Chen, Long; Guo, Zhaoqi; Nagai, Atsushi; Jiang, Donglin

    2011-11-09

    Herein we report a strategy for the design of highly luminescent conjugated polymers by restricting rotation of the polymer building blocks through a microporous network architecture. We demonstrate this concept using tetraphenylethene (TPE) as a building block to construct a light-emitting conjugated microporous polymer. The interlocked network successfully restricted the rotation of the phenyl units, which are the major cause of fluorescence deactivation in TPE, thus providing intrinsic luminescence activity for the polymers. We show positive "CMP effects" that the network promotes π-conjugation, facilitates exciton migration, and improves luminescence activity. Although the monomer and linear polymer analogue in solvents are nonemissive, the network polymers are highly luminescent in various solvents and the solid state. Because emission losses due to rotation are ubiquitous among small chromophores, this strategy can be generalized for the de novo design of light-emitting materials by integrating the chromophores into an interlocked network architecture.

  15. Synthesis, characterization and in vitro cytotoxicity evaluation of polyamidoamine conjugate containing pamidronate and platinum drug

    CSIR Research Space (South Africa)

    Ndamase, AS

    2018-02-01

    Full Text Available Bisphosphonates have been found to be effective when combined with anticancer drugs for chemotherapy. In this paper, pamidronate and platinum complexes were conjugated to linear poly(amidoamine)s (PAMAM) to improve the drug efficacy. The conjugates...

  16. Threshold couplings of phase-conjugate mirrors with two interaction regions.

    Science.gov (United States)

    Beli, M; Petrovi, M; Sandfuchs, O; Kaiser, F

    1998-03-01

    Using the grating-action method, we determine the threshold coupling strengths of three generic examples of phase-conjugate mirrors with two interaction regions: the cat conjugator, the mutually incoherent beam coupler, and the interconnected ring mirror.

  17. Conjugated polymer shells on colloidal templates by seeded Suzuki–Miyaura dispersion polymerization.

    Science.gov (United States)

    ten Hove, Jan Bart; Appel, Jeroen; van den Broek, Johanna M; Kuehne, Alexander J C; Sprakel, Joris

    2014-03-12

    The self-assembly of colloidal conjugated polymers presents a versatile and powerful oute towards new functional optoelectronic materials and devices. However, this strategy relies on the existence of chemical protocols to prepare highly monodisperse colloids of conjugated polymers in high yields. Here, a recently developed Suzuki–Miyaura dispersion polymerization method is adopted to synthesize core–shell particles, in which a conjugated polymer shell is grown onto non-conjugated organic and inorganic colloidal templates. By chemically anchoring aryl halide groups at the particle surface, a conjugated polymer shell can be attached to a wide variety of organic and inorganic microparticles. In this way, both spherical and non-spherical hybrid conjugated polymer particles are prepared, and it is shown that the method can be applied to a variety of conjugated polymers. This new method offers independent control of the size, shape and photophysical properties of these novel conjugated polymer particles.

  18. Metal chelate conjugated monoclonal antibodies, wherein the metal is an α emitter

    International Nuclear Information System (INIS)

    Gansow, O.A.; Strand, M.

    1984-01-01

    Methods of manufacturing and purifying metal chelate conjugated monoclonal antibodies are described, wherein the chelated metal emits alpha radiation. The conjugates are suited for therapeutic uses being substantially free of nonchelated radiometal. (author)

  19. The Composition of the Cell Envelope Affects Conjugation in Bacillus subtilis

    OpenAIRE

    Johnson, Christopher M; Grossman, Alan Davis

    2016-01-01

    Conjugation in bacteria is the contact-dependent transfer of DNA from one cell to another via donor-encoded conjugation machinery. It is a major type of horizontal gene transfer between bacteria. Conjugation of the integrative and conjugative element ICEBs1 into Bacillus subtilis is affected by the composition of phospholipids in the cell membranes of the donor and recipient. We found that reduction (or elimination) of lysyl-phosphatidylglycerol caused by loss of mprF caused a decrease in con...

  20. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis

    OpenAIRE

    Jain, S. K.; Gill, M. S.; Pawar, H. S.; Suresh, Sarasija

    2014-01-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; st...

  1. Preliminary experiments on phase conjugation for flow visualization. [barium titanate single crystals

    Science.gov (United States)

    Weimer, D.; Howes, W. L.

    1984-01-01

    Barium titanate single crystals are discussed in the context of: the procedure for polarizing a crystal; a test for phase conjugation; transients in the production of phase conjugation; real time readout by a separate laser of a hologram induced within the crystal, including conjugation response times to on-off switching of each beam; and a demonstration of a Twyman-Green interferometer utilizing phase conjugation.

  2. Effect of conjugated linoleic acid (CLA) on the performance and ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the protective effect of dietary conjugated linoleic acid (CLA) on the prevention of aflatoxin B1) (AFB1) toxicity in the ... and serum levels of total protein, total albumin, uric acid, alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

  3. Synthesis and characterization of nido-carborane-cobalamin conjugates

    International Nuclear Information System (INIS)

    Hogenkamp, Harry P.C.; Collins, Douglas A.; Live, David; Benson, Linda M.; Naylor, Stephen

    2000-01-01

    Three vitamin B 12 (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as 11 B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B 12 binding capacity assay. When compared with 57 Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10 B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy

  4. A little less conjugation, a little more accuracy

    Science.gov (United States)

    2016-02-01

    The modification of proteins with fluorophores, drugs and polymers is required for many applications, yet conjugation reactions often generate a heterogeneous mixture of products. A collection of articles in this issue focuses on methods to modify proteins in a site-selective manner.

  5. Cu2+ or Fe3+ Terpyridine/Aptamer Conjugates

    NARCIS (Netherlands)

    Biniuri, Yonatan; Albada, Bauke; Wolff, Mariusz; Golub, Eyal; Gelman, Dmitri; Willner, Itamar

    2018-01-01

    A concept to tailor catalytic nucleic acid structures is introduced. The method involves the covalent conjugation of catalytically active metal ion complexes to sequence-specific ligand-binding nucleic acids (aptamers) yielding hybrids termed "nucleoapzymes" that act as enzyme-mimicking nucleic acid

  6. Adaptive Regularization of Neural Networks Using Conjugate Gradient

    DEFF Research Database (Denmark)

    Goutte, Cyril; Larsen, Jan

    1998-01-01

    Andersen et al. (1997) and Larsen et al. (1996, 1997) suggested a regularization scheme which iteratively adapts regularization parameters by minimizing validation error using simple gradient descent. In this contribution we present an improved algorithm based on the conjugate gradient technique........ Numerical experiments with feedforward neural networks successfully demonstrate improved generalization ability and lower computational cost...

  7. Nanobody-photosensitizer conjugates for targeted photodynamic therapy

    NARCIS (Netherlands)

    Heukers, Raimond; van Bergen en Henegouwen, P; Oliveira, Sabrina

    2014-01-01

    Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an attempt

  8. Asymmetric Conjugate Addition of Grignard Reagents to Pyranones

    NARCIS (Netherlands)

    Mao, Bin; Fananas Mastral, Martin; Feringa, Ben L.

    2013-01-01

    An efficient enantioselective synthesis of lactones was developed based on the catalytic asymmetric conjugate addition (ACA) of alkyl Grignard reagents to pyranones. The use of 2H-pyran-2-one for the first time in the ACA with Grignard reagents allows for a variety of further transformations to

  9. Self-assembly behaviour of conjugated terthiophene surfactants in water

    NARCIS (Netherlands)

    van Rijn, Patrick; Janeliunas, Dainius; Brizard, Aurelie M.; Stuart, Marc C. A.; Koper, Ger J. M.; Eelkema, Rienk; van Esch, Jan H.

    2011-01-01

    Conjugated self-assembled systems in water are of great interest because of their potential application in biocompatible supramolecular electronics, but so far their supramolecular chemistry remains almost unexplored. Here we present amphiphilic terthiophenes as a general self-assembling platform

  10. Diversity of (dihydro) hydroxycinnamic acid conjugates in Colombian potato tubers

    NARCIS (Netherlands)

    Narvaez Cuenca, C.E.; Vincken, J.P.; Zheng, Chaoya; Gruppen, H.

    2013-01-01

    In potato tuber, caffeic acid (the predominant hydroxycinnamic acid (HCA)), its conjugates (HCAcs; i.e. chlorogenic acid (ChA), crypto-ChA, and neo-ChA), and anthocyanin-linked HCAs have been extensively described in the literature. In contrast, only little information is available on the occurrence

  11. Displacement of polarons by vibrational modes in doped conjugated polymers

    NARCIS (Netherlands)

    Anderson, M.; Ramanan, C.; Fontanesi, C.; Frick, A.; Surana, S.; Cheyns, D.; Furno, M.; Keller, T.; Allard, S.; Scherf, U.; Beljonne, D.; D'Avino, G.; von Hauff, E.; Da Como, E.

    2017-01-01

    Organic pi-conjugated polymers are deemed to be soft materials with strong electron-phonon coupling, which results in the formation of polarons, i.e., charge carriers dressed by self-localized distortion of the nuclei. Universal signatures for polarons are optical resonances below the band gap and

  12. Efficient Electroluminescence from a New Conjugated Rigid-Rod Polyquinoline

    National Research Council Canada - National Science Library

    Zhang, Xuejun, Ph.D

    1998-01-01

    A new conjugated rigid-rod polyquinoline, poly (2,2'-p-phenylene)-6,6'-bis(4-(p-tert-butylphenyl)quinoline)), was synthesized and its thin film was used as the emissive layer in light-emitting diodes...

  13. A Developmental History of the Hispano-Romance Verb Conjugations

    Science.gov (United States)

    Stovicek, Thomas William

    2010-01-01

    This study outlines the development of Portuguese and Spanish verbal morphology from Latin in the context of the Hispanic branch of Romance, with a focus on the conjugational classes, whose number has been reduced to only three in this branch of Western Romance. It is innovative in approaching the topic as a study of sequential productive grammars…

  14. Polyphenol-chitosan conjugates: Synthesis, characterization, and applications.

    Science.gov (United States)

    Hu, Qiaobin; Luo, Yangchao

    2016-10-20

    Chitosan, the only positively charged polysaccharide in the world, is very attractive for food, medicinal and pharmaceutical applications because of its promising properties, including non-toxicity, superb biodegradability, high biocompatibility, abundant availability and low cost. In order to overcome the poor water solubility and widen the applications of chitosan, various polyphenol-chitosan conjugates have been synthesized in recent years. The present review focuses on the chitosan-based conjugates formed using different polyphenols, including gallic acid, caffeic acid, ferulic acid, salicylic acid, catechin, and EGGE, etc. Three major synthesis techniques, namely, activated ester-mediated modification, enzyme-mediated strategy, and free radical induced grafting approach are introduced in detail. In addition, the new physicochemical and biological properties of polyphenol-chitosan conjugates are introduced, including water solubility, thermo stability, in vitro and in vivo antioxidant activity, antimicrobial and anticancer activity. Furthermore, the novel applications of each conjugate are discussed in detail. Lastly, the challenges and prospective areas of study related to polyphenol-chitosan are summarized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Effect of methionine and glucosamine conjugation on the anticancer ...

    Indian Academy of Sciences (India)

    ... methionine conjugated aromatic dinitrobenzamide mustard of 2-chlorobenzoic acid is the most effective one. It acts by inducing apoptosis through G2/M phase arrest and encouragingly, is much less toxic to nontumorigenic human embryonic kidney (HEK-293T) and mouse embryonic fibroblast (NIH 3T3) cell lines in vitro.

  16. New pneumococcal conjugate vaccine introductions in four sub ...

    African Journals Online (AJOL)

    Background: Pneumonia is a main cause of under-five mortality in low-income settings. The pneumococcal conjugate vaccine (PCV) has been introduced in many countries as a tool in the disease's prevention. Although PCV's effectiveness has been established, less is known about the effects of introducing additional ...

  17. On-axis conoscopic holography without a conjugate image.

    Science.gov (United States)

    Mugnier, L M; Sirat, G Y

    1992-02-15

    We present a method for removing the conjugate image in an incoherent-light holographic technique, namely, on-axis conoscopic holography. The point-spread function that we obtain is that of a complex Gabor zone pattern, which thus should allow good-quality reconstructions of objects. Experimental results are also presented, which confirm the validity of this method.

  18. Propargylamine-isothiocyanate reaction: efficient conjugation chemistry in aqueous media

    DEFF Research Database (Denmark)

    Viart, Helene Marie-France; Larsen, T. S.; Tassone, Chiara

    2014-01-01

    A coupling reaction between secondary propargyl amines and isothiocyanates in aqueous media is described. The reaction is high-yielding and affords cyclized products within 2-24 h. A functionalized ether lipid was synthesized in 8 steps, formulated as liposomes with POPC and conjugated to FITC un...

  19. Direct measurement of the microscale conductivity of conjugated polymer monolayers

    DEFF Research Database (Denmark)

    Bøggild, Peter; Grey, Francois; Hassenkam, T.

    2000-01-01

    The in-plane conductivity of conjugated polymer monolayers is mapped here for the first time on the microscale using a novel scanning micro four-point probe (see Figure). The probe allows the source, drain, and voltage electrodes to be positioned within the same domain and the mapping results...

  20. Nonnatural amino acids for site-specific protein conjugation

    NARCIS (Netherlands)

    Graaf, Albert J. de; Kooijman, M.; Hennink, W.E.; Mastrobattista, E.

    2009-01-01

    Over the years, several chemical reactions have been developed that enable the covalent conjugation of synthetic molecules to natural proteins. The resulting bioconjugates have become important tools in the study of natural proteins. Furthermore, they form a new class of protein-based

  1. Homology among tet determinants in conjugative elements of streptococci

    Energy Technology Data Exchange (ETDEWEB)

    Smith, M.D.; Hazum, S.; Guild, W.R.

    1981-10-01

    A mutation to tetracycline sensitivity in a resistant strain of Streptococcus pneumoniae was shown by several criteria to be due to a point mutation in the conjugative o(cat-tet) element found in the chromosomes of strains derived from BM6001, a clinical strain resistant to tetracycline and chloramphenicol. Strains carrying the mutation were transformed back to tetracycline resistance with the high efficiency of a point marker by donor deoxyribonucleic acids from its ancestral strain and from nine other clinical isolates of pneumococcus and by deoxyribonucleic acids from Group D Streptococcus faecalis and Group B Streptococcus agalactiae strains that also carry conjugative tet elements in their chromosomes. It was not transformed to resistance by tet plasmid deoxyribonucleic acids from either gram-negative or gram-positive species, except for one that carried transposon TN916, the conjugative tet element present in the chromosomes of some S. faecalis strains. The results showed that the tet determinants in conjugative elements of several streptococcal species share a high degree of deoxyribonucleic acid sequence homology and suggested that they differ from other tet genes.

  2. Antiobesity mechanisms of action of conjugated linoleic acid

    DEFF Research Database (Denmark)

    Kennedy, Arion; Martinez, Kristina; Schmidt, Soren

    2010-01-01

    Conjugated linoleic acid (CLA), a family of fatty acids found in beef, dairy foods and dietary supplements, reduces adiposity in several animal models of obesity and some human studies. However, the isomer-specific antiobesity mechanisms of action of CLA are unclear, and its use in humans...

  3. Structure and function of nanoparticle-protein conjugates

    International Nuclear Information System (INIS)

    Aubin-Tam, M-E; Hamad-Schifferli, K

    2008-01-01

    Conjugation of proteins to nanoparticles has numerous applications in sensing, imaging, delivery, catalysis, therapy and control of protein structure and activity. Therefore, characterizing the nanoparticle-protein interface is of great importance. A variety of covalent and non-covalent linking chemistries have been reported for nanoparticle attachment. Site-specific labeling is desirable in order to control the protein orientation on the nanoparticle, which is crucial in many applications such as fluorescence resonance energy transfer. We evaluate methods for successful site-specific attachment. Typically, a specific protein residue is linked directly to the nanoparticle core or to the ligand. As conjugation often affects the protein structure and function, techniques to probe structure and activity are assessed. We also examine how molecular dynamics simulations of conjugates would complete those experimental techniques in order to provide atomistic details on the effect of nanoparticle attachment. Characterization studies of nanoparticle-protein complexes show that the structure and function are influenced by the chemistry of the nanoparticle ligand, the nanoparticle size, the nanoparticle material, the stoichiometry of the conjugates, the labeling site on the protein and the nature of the linkage (covalent versus non-covalent)

  4. Maternal Conjugal Multiplicity and Child Development in Rural Jamaica

    Science.gov (United States)

    Dreher, Melanie; Hudgins, Rebekah

    2010-01-01

    Using field-based observations and standardized measures of the home environment and child development, the authors followed 59 rural Jamaican women and their offspring from birth to age 5. The findings suggest that conjugal multiplicity, a female reproductive pattern characterized by multiple unions, maternal unmarried status, and absent father,…

  5. Excitons in conjugated polymers: Do we need a paradigma change?

    Energy Technology Data Exchange (ETDEWEB)

    Beenken, Wichard J.D. [Department of Theoretical Physics I, Ilmenau University of Thechnology (Germany)

    2009-12-15

    We have previously shown that both, polymer conformation and dynamics are crucial for the exciton transport in conjugated polymers. Thereby we found that the usual Foerster-type hopping transfer model - even if one applies the line-dipole approximation - falls short in one crucial aspect: the nature of the sites the excitons are transferred between is still unclear. We found that the simple model of spectroscopic units defined as segments of the polymer chains separated by structural defects breaking the {pi}-conjugation is only justified for chemical defects like hydrogenated double bonds, or extreme gauche (90 ) torsions between the monomers. Both defects are far too rare in a well-prepared conjugated polymer to explain the mean spectroscopic-unit length of typically 6-7 monomers. Meanwhile, also the concept of dynamical formation of the spectroscopic units, we had previously suggested, has also failed. Thus the question of a paradigma change concerning the exciton transport in conjugated polymers appears on the agenda. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  6. Rapid, facile synthesis of conjugated polymer zwitterions in ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Page, Zachariah A. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Liu, Feng [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Russell, Thomas P. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Emrick, Todd [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA

    2014-01-01

    Ionic liquids (ILs) were utilized for the rapid air-stable Suzuki polymerization of polar zwitterionic thiophene monomers, precluding the need for volatile organic solvents, phosphine ligands and phase transfer catalysts typically used in conjugated polymer synthesis.

  7. From Support to Control: A Configurational Perspective on Conjugal Quality

    Science.gov (United States)

    Widmer, Eric D.; Giudici, Francesco; Le Goff, Jean-Marie; Pollien, Alexandre

    2009-01-01

    The topic of conjugal quality provides an empirical illustration of the relevance of the configurational perspective on families. On the basis of a longitudinal sample of 1,534 couples living in Switzerland drawn from the study "Social Stratification, Cohesion and Conflict in Contemporary Families," we show that various types of…

  8. Conception on maleness within conjugal and sexual contexts and ...

    African Journals Online (AJOL)

    Conception on maleness within conjugal and sexual contexts and involvement in family planning /household tasks among males in delta state. ... On the basis of the findings, it was recommended that the nation's educational curricular be reviewed to include teachings that will encourage men to participate in household ...

  9. The Effects of Conjugated Linoleic Acid on the Performance of ...

    African Journals Online (AJOL)

    rahim

    Abstract. The objective of this study was to determine the effects of the long-term feeding of conjugated linoleic acid (CLA) on laying hen performance, egg fertility and hatchability of fertile eggs of Japanese quail. (Coturnix coturnix japonica). One hundred and sixty 7-day old Japanese quail chicks were randomly assigned to ...

  10. Deflation in preconditioned conjugate gradient methods for Finite Element Problems

    NARCIS (Netherlands)

    Vermolen, F.J.; Vuik, C.; Segal, A.

    2002-01-01

    We investigate the influence of the value of deflation vectors at interfaces on the rate of convergence of preconditioned conjugate gradient methods applied to a Finite Element discretization for an elliptic equation. Our set-up is a Poisson problem in two dimensions with continuous or discontinuous

  11. Parallel conjugate gradient algorithms for manipulator dynamic simulation

    Science.gov (United States)

    Fijany, Amir; Scheld, Robert E.

    1989-01-01

    Parallel conjugate gradient algorithms for the computation of multibody dynamics are developed for the specialized case of a robot manipulator. For an n-dimensional positive-definite linear system, the Classical Conjugate Gradient (CCG) algorithms are guaranteed to converge in n iterations, each with a computation cost of O(n); this leads to a total computational cost of O(n sq) on a serial processor. A conjugate gradient algorithms is presented that provide greater efficiency using a preconditioner, which reduces the number of iterations required, and by exploiting parallelism, which reduces the cost of each iteration. Two Preconditioned Conjugate Gradient (PCG) algorithms are proposed which respectively use a diagonal and a tridiagonal matrix, composed of the diagonal and tridiagonal elements of the mass matrix, as preconditioners. Parallel algorithms are developed to compute the preconditioners and their inversions in O(log sub 2 n) steps using n processors. A parallel algorithm is also presented which, on the same architecture, achieves the computational time of O(log sub 2 n) for each iteration. Simulation results for a seven degree-of-freedom manipulator are presented. Variants of the proposed algorithms are also developed which can be efficiently implemented on the Robot Mathematics Processor (RMP).

  12. Effect of dietary conjugated linoleic acid (CLA) on the metabolism ...

    African Journals Online (AJOL)

    Effect of dietary conjugated linoleic acid (CLA) on the metabolism and reproduction of dairy cows. ... South African Journal of Animal Science ... This study confirms the positive effects of dietary CLA supplementation on the metabolism, by improving the energy intake and reducing the negative energy balance. Moreover, the ...

  13. Construction of intergeneric conjugal transfer for molecular genetic ...

    African Journals Online (AJOL)

    SAM

    2014-03-26

    Mar 26, 2014 ... To facilitate molecular studies of Streptomyces mobaraensis producing transglutaminase, an effective transformation method was established via intergeneric conjugal transfer using Escherichia coli. ET12567 harboring the ØC31-derived integration vector, pSET152. The highest frequency was attained.

  14. Convexity of spheres in a manifold without conjugate points

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    Abstract. For a non-compact, complete and simply connected manifold M without conjugate points, we prove that if the determinant of the second fundamental form of the geodesic spheres in M is a radial function, then the geodesic spheres are convex. We also show that if M is two or three dimensional and without ...

  15. Construction of intergeneric conjugal transfer for molecular genetic ...

    African Journals Online (AJOL)

    To facilitate molecular studies of Streptomyces mobaraensis producing transglutaminase, an effective transformation method was established via intergeneric conjugal transfer using Escherichia coli ET12567 harboring the ØC31-derived integration vector, pSET152. The highest frequency was attained on ISP4 medium ...

  16. The Lanczos and Conjugate Gradient Algorithms in Finite Precision Arithmetic

    Czech Academy of Sciences Publication Activity Database

    Meurant, G.; Strakoš, Zdeněk

    2006-01-01

    Roč. 15, - (2006), s. 471-542 ISSN 0962-4929 R&D Projects: GA AV ČR 1ET400300415 Institutional research plan: CEZ:AV0Z10300504 Keywords : Lanczos method * conjugate gradient method * finite precision arithmetic * numerical stability * iterative methods Subject RIV: BA - General Mathematics

  17. Synthesis and characterization of nido-carborane-cobalamin conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Hogenkamp, Harry P.C. E-mail: hogen001@tc.umn.edu; Collins, Douglas A.; Live, David; Benson, Linda M.; Naylor, Stephen

    2000-01-01

    Three vitamin B{sub 12} (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as {sup 11}B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B{sub 12} binding capacity assay. When compared with {sup 57}Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the {sup 10}B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy.

  18. Cross Reactive Material 197 glycoconjugate vaccines contain privileged conjugation sites.

    Science.gov (United States)

    Möginger, Uwe; Resemann, Anja; Martin, Christopher E; Parameswarappa, Sharavathi; Govindan, Subramanian; Wamhoff, Eike-Christian; Broecker, Felix; Suckau, Detlev; Pereira, Claney Lebev; Anish, Chakkumkal; Seeberger, Peter H; Kolarich, Daniel

    2016-02-04

    Production of glycoconjugate vaccines involves the chemical conjugation of glycans to an immunogenic carrier protein such as Cross-Reactive-Material-197 (CRM197). Instead of using glycans from natural sources recent vaccine development has been focusing on the use of synthetically defined minimal epitopes. While the glycan is structurally defined, the attachment sites on the protein are not. Fully characterized conjugates and batch-to-batch comparisons are the key to eventually create completely defined conjugates. A variety of glycoconjugates consisting of CRM197 and synthetic oligosaccharide epitopes was characterised using mass spectrometry techniques. The primary structure was assessed by combining intact protein MALDI-TOF-MS, LC-MALDI-TOF-MS middle-down and LC-ESI-MS bottom-up approaches. The middle-down approach on CNBr cleaved glycopeptides provided almost complete sequence coverage, facilitating rapid batch-to-batch comparisons, resolving glycan loading and identification of side products. Regions close to the N- and C-termini were most efficiently conjugated.

  19. Bis(pyrrole-benzimidazole) conjugates as novel colorimetric sensor ...

    Indian Academy of Sciences (India)

    Sanjeev Pran Mahanta

    Bis(pyrrole-benzimidazole) conjugates as novel colorimetric sensor for anions. SANJEEV PRAN MAHANTAa,b,∗ and PRADEEPTA KUMAR PANDAb,∗. aDepartment of Chemical Sciences, Tezpur University, Napaam, Assam 784 028, India. bSchool of Chemistry, University of Hyderabad, Hyderabad, Telengana 500 046, ...

  20. Expeditious synthesis of coumarin-pyridone conjugates molecules ...

    Indian Academy of Sciences (India)

    RAJNI KHAJURIA

    2017-09-06

    Sep 6, 2017 ... important character in amyloid formation in Alzheimer's disease.19. Further, in the design of new pharmaceutical agents, the development of conjugate molecules through the combination of different pharmacophores has resulted in the improvement of biological profiles. Adopting this approach, several ...

  1. Fullerene–biomolecule conjugates and their biomedicinal applications

    Directory of Open Access Journals (Sweden)

    Yang X

    2013-12-01

    Full Text Available Xinlin Yang,1 Ali Ebrahimi,1 Jie Li,1,2 Quanjun Cui11Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA; 2School of Materials Science, Beijing Institute of Technology, Beijing, People's Republic of ChinaAbstract: Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene–biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene–biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene–biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.Keywords: fullerene, amino acid, peptide, oligonucleotide, sugar, ester

  2. Synthesis of regioregular pentacene-containing conjugated polymers

    KAUST Repository

    Okamoto, Toshihiro

    2011-01-01

    We report the synthesis and characterization of a new class of regioregular pentacene-containing conjugated polymers via our synthetic routes reported previously. We found that our regioregular pentacene polymers showed improved ordering than their regiorandom counterpart as well as ambipolar OFET performance. © 2011 The Royal Society of Chemistry.

  3. A nanodiamond-fluorescein conjugate for cell studies

    Science.gov (United States)

    Pedroso-Santana, Seidy; Fleitas-Salazar, Noralvis; Sarabia-Sainz, Andrei; Silva-Campa, Erika; Burgara-Estrella, Alexel; Angulo-Molina, Aracely; Melendrez, Rodrigo; Pedroza-Montero, Martin; Riera, Raul

    2018-03-01

    The use of nanodiamonds in studies with living systems generally involves the modification of their surfaces with functional groups. Fluorescent molecules can be attached to these groups, so that one can know the exact position of the particles in each moment of the interaction with the cells. Here we modify the surface of detonation nanodiamonds and nitrogen-vacancy center nanodiamonds using carboxylation and hydroxylation procedures. Subsequent reactions with silicates and cysteine, before addition of fluorescein allow to obtain fluorescent nano-conjugates. We used confocal microscopy to observe the position of nanodiamonds interacting with HeLa cells. At 3 h post-incubation the green fluorescence is localized in extracellular rounded like-vesicles assemblies while at 24 h the conjugates can be observed inside the cells. The measurement of the fluorescence emitted by both conjugates allowed to find an enhanced emission of fluorescein isothiocyanate (FITC) when the nitrogen-vacancy center is present. We propose the existence of a fluorescence enhancement by electron transference process. The procedure described in this work allows the functionalization of nanodiamonds with FITC and other molecules using functional surface groups and small size mediators. Also, as was proved in our work, the nanodiamond-fluorescein conjugates can be used to track nanoparticles position within the cell. Localization studies are particularly important for drug delivery applications of nanodiamonds.

  4. Bis(pyrrole-benzimidazole) conjugates as novel colorimetric sensor ...

    Indian Academy of Sciences (India)

    Sanjeev Pran Mahanta

    Abstract. Novel bis(pyrrole-benzimidazole) (PYBI) conjugates were investigated as colorimetric anion recognition motif by employing multiple donor sites. In this regard, PYBI derivatives where pyrrole unit is connected to the C2 position of benzimidazole via its α-position were synthesized and their anion recognition.

  5. Intergenic and intragenic conjugal transfer of multiple antibiotic ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-01-19

    Jan 19, 2009 ... Conjugation process was conducted to determine the means of transferring multiple loci of antibiotic resistant gene among bacteria in the surface water of Bangladesh. Our observation demonstrated that tetracycline resistant gene can be spread between bacteria in the aquatic environment. In this study, it.

  6. Technology of DTPA and immunoglobulins conjugation and their attachment to 90Y and 177Lu radionuclides

    International Nuclear Information System (INIS)

    Rekova, M.; Jedinakova-Krizova, V.

    2010-01-01

    The aim of the study of labeling of ligand-antibody conjugates was to find optimal conditions of preparing of these conjugates and appropriate radioactivity of selected nuclide for applications in nuclear medicine. Conjugation of the γ-immunoglobulin G (human or bovine IgG, polyclonal antibodies) and bifunctional chelating agent, diethylenetriaminepentaacetic acid dianhydride (cDTPAA), was carried out. Various values of the cDTPAA/antibody ratio, the weight concentration of polyclonal or monoclonal antibodies (MEM-97) and buffers were used. Further, the labeling conditions of the DTPA-IgG conjugate by radionuclides 90 Y and 177 Lu were optimized, and the labeling yield and the conjugation ratio of prepared radionuclide-DTPA-IgG conjugates was determined. Optimal incubation time of the immunoglobulin conjugation was obtained at 30 min from mixing of individual components. The labeling yield of radionuclide-DTPA-antibody conjugate higher than 95% was achieved. Higher values of conjugation ratio of radionuclide-DTPA-antibody conjugate were achieved in 0.1 mol L -1 carbonate buffer, pH 8.5, and the 0.1 mol L -1 carbonate buffer is suitable for studied conjugation systems. This study showed that the labeling yield as well as the conjugation ratio of tested systems depend on the amount of antibody substance, bifunctional chelating agent/antibody molar ratio and pH value of the buffer used. (author)

  7. Covalently bound conjugates of albumin and heparin: Synthesis, fractionation and characterization

    NARCIS (Netherlands)

    Hennink, Wim E.; Feijen, Jan; Ebert, Charles D.; Kim, Sung Wan

    1983-01-01

    Covalently bound conjugates of human serum albumin and heparin were prepared as compounds which could improve the blood-compatibility of polymer surfaces either by preadsorption or by covalent coupling of the conjugates onto blood contacting surfaces. The conjugates (10–16 weight % of heparin) were

  8. Influence of fungal-bacterial interactions on bacterial conjugation in the residuesphere

    NARCIS (Netherlands)

    Sengelov, G.; Kowalchuk, G.A.; Sørensen, S.J.

    2000-01-01

    Conjugal gene transfer among bacteria in the residuesphere (area between decaying plant material and soil) of leaves of barley straw was studied. The residuesphere was shown to be a hot-spot for conjugal gene transfer compared to conjugation in sterile sand and non-sterile bulk soil. Impact of

  9. Diclofenac in Arabidopsis cells: Rapid formation of conjugates.

    Science.gov (United States)

    Fu, Qiuguo; Ye, Qingfu; Zhang, Jianbo; Richards, Jaben; Borchardt, Dan; Gan, Jay

    2017-03-01

    Pharmaceutical and personal care products (PPCPs) are continuously introduced into the soil-plant system, through practices such as agronomic use of reclaimed water and biosolids containing these trace contaminants. Plants may accumulate PPCPs from soil, serving as a conduit for human exposure. Metabolism likely controls the final accumulation of PPCPs in plants, but is in general poorly understood for emerging contaminants. In this study, we used diclofenac as a model compound, and employed 14 C tracing, and time-of-flight (TOF) and triple quadruple (QqQ) mass spectrometers to unravel its metabolism pathways in Arabidopsis thaliana cells. We further validated the primary metabolites in Arabidopsis seedlings. Diclofenac was quickly taken up into A. thaliana cells. Phase I metabolism involved hydroxylation and successive oxidation and cyclization reactions. However, Phase I metabolites did not accumulate appreciably; they were instead rapidly conjugated with sulfate, glucose, and glutamic acid through Phase II metabolism. In particular, diclofenac parent was directly conjugated with glutamic acid, with acyl-glutamatyl-diclofenac accounting for >70% of the extractable metabolites after 120-h incubation. In addition, at the end of incubation, >40% of the spiked diclofenac was in the non-extractable form, suggesting extensive sequestration into cell matter. The rapid formation of non-extractable residue and dominance of diclofenac-glutamate conjugate uncover previously unknown metabolism pathways for diclofenac. In particular, the rapid conjugation of parent highlights the need to consider conjugates of emerging contaminants in higher plants, and their biological activity and human health implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Bacteriophages limit the existence conditions for conjugative plasmids.

    Science.gov (United States)

    Harrison, Ellie; Wood, A Jamie; Dytham, Calvin; Pitchford, Jonathan W; Truman, Julie; Spiers, Andrew; Paterson, Steve; Brockhurst, Michael A

    2015-06-02

    Bacteriophages are a major cause of bacterial mortality and impose strong selection on natural bacterial populations, yet their effects on the dynamics of conjugative plasmids have rarely been tested. We combined experimental evolution, mathematical modeling, and individual-based simulations to explain how the ecological and population genetics effects of bacteriophages upon bacteria interact to determine the dynamics of conjugative plasmids and their persistence. The ecological effects of bacteriophages on bacteria are predicted to limit the existence conditions for conjugative plasmids, preventing persistence under weak selection for plasmid accessory traits. Experiments showed that phages drove faster extinction of plasmids in environments where the plasmid conferred no benefit, but they also revealed more complex effects of phages on plasmid dynamics under these conditions, specifically, the temporary maintenance of plasmids at fixation followed by rapid loss. We hypothesized that the population genetic effects of bacteriophages, specifically, selection for phage resistance mutations, may have caused this. Further mathematical modeling and individual-based simulations supported our hypothesis, showing that conjugative plasmids may hitchhike with phage resistance mutations in the bacterial chromosome. Conjugative plasmids are infectious loops of DNA capable of transmitting DNA between bacterial cells and between species. Because plasmids often carry extra genes that allow bacteria to live in otherwise-inhospitable environments, their dynamics are central to understanding bacterial adaptive evolution. The plasmid-bacterium interaction has typically been studied in isolation, but in natural bacterial communities, bacteriophages, viruses that infect bacteria, are ubiquitous. Using experiments, mathematical models, and computer simulations we show that bacteriophages drive plasmid dynamics through their ecological and evolutionary effects on bacteria and ultimately

  11. Naproxen glycine conjugate-synthesis, pharmaceutical preformulation and pharmacodynamic evaluation.

    Science.gov (United States)

    Mishra, Ashutosh; Agrawal, Shalini; Pathak, Kamla

    2012-02-01

    The project was aimed at synthesizing and characterizing amino acid conjugate of naproxen (categorically stated as Type II A prodrug) that is expected to enhance solubility without affecting permeability and is capable of delivering naproxen (NAP) to colon without significant reversion of prodrug in gastrointestinal conditions. Thus, naproxen-glycine conjugate (NAP-GLY) was prepared by conventional coupling method and the prodrug was characterized by FTIR, FTNMR, FAB mass and elemental analysis. The conjugate was then subjected to selected pharmaceutical preformulation studies like pH-solubility analysis, intrinsic dissolution rate and pH partition studies. These studies established 1.24 folds higher solubility of the (NAP-GLY) over NAP in phosphate buffer pH 7.4 without compromising its partitioning ability. The amino acid conjugate demonstrated superior intrinsic dissolution capabilities (30.9% enhancement) than NAP and in vitro reversion studies suggested its potential of safe transit to colon where the moiety is capable of reverting to 78.52% NAP after 72 hrs of the experiment. In vivo evaluation of NAP-GLY in experimentally induced colitis established its efficacy an anti-inflammatory prodrug moiety (ulcer index = 6.73 with respect to 42.5 for control) that was supported by histological studies. In addition to its ability to control colonic ulcers NAP-GLY demonstrated insignificant (P >0.05) gastric ulcerogenic potential. Conclusively, the conjugate when suitably formulated can be considered as therapeutically efficacious drug delivery system with fewer pharmaceutical limitations. © 2012 Informa Healthcare USA, Inc.

  12. Generic method for the absolute quantification of glutathione S-conjugates : Application to the conjugates of acetaminophen, clozapine and diclofenac

    NARCIS (Netherlands)

    den Braver, Michiel W.; Vermeulen, Nico P.E.; Commandeur, Jan N.M.

    2017-01-01

    Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione

  13. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Directory of Open Access Journals (Sweden)

    Jacob Thomas

    Full Text Available Integrative and conjugative elements (ICEs are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP, encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  14. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Science.gov (United States)

    Thomas, Jacob; Lee, Catherine A; Grossman, Alan D

    2013-01-01

    Integrative and conjugative elements (ICEs) are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT) by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP), encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  15. Preparation of bioconjugates by solid-phase conjugation to ion exchange matrix-adsorbed carrier proteins

    DEFF Research Database (Denmark)

    Houen, G.; Olsen, D.T.; Hansen, P.R.

    2003-01-01

    of ovalbumin and various peptides were prepared in a similar manner and used for production of peptide antisera by direct immunization with the conjugates bound to the ion exchanger. Advantages of the method are its solid-phase nature, allowing fast and efficient reactions and intermediate washings......, and immunization experiments with the eluted conjugates showed that the more substituted conjugates gave rise to the highest titers of glutathione antibodies. Direct immunization with the conjugates adsorbed to the ion exchange matrix was possible and gave rise to high titers of glutathione antibodies. Conjugates...

  16. Axial range of conjugate adaptive optics in two-photon microscopy.

    Science.gov (United States)

    Paudel, Hari P; Taranto, John; Mertz, Jerome; Bifano, Thomas

    2015-08-10

    We describe an adaptive optics technique for two-photon microscopy in which the deformable mirror used for aberration compensation is positioned in a plane conjugate to the plane of the aberration. We demonstrate in a proof-of-principle experiment that this technique yields a large field of view advantage in comparison to standard pupil-conjugate adaptive optics. Further, we show that the extended field of view in conjugate AO is maintained over a relatively large axial translation of the deformable mirror with respect to the conjugate plane. We conclude with a discussion of limitations and prospects for the conjugate AO technique in two-photon biological microscopy.

  17. Identification of host genes that affect acquisition of an integrative and conjugative element in Bacillus subtilis

    Science.gov (United States)

    Johnson, Christopher M.; Grossman, Alan D.

    2014-01-01

    Summary Conjugation, a major type of horizontal gene transfer in bacteria, involves transfer of DNA from a donor to a recipient using donor-encoded conjugation machinery. Using a high throughput screen (Tn-seq), we identified genes in recipients that contribute to acquisition of the integrative and conjugative element ICEBs1 by Bacillus subtilis. We found that null mutations in some genes caused an increase, and others a decrease in conjugation efficiency. Some mutations affected conjugation only when present in recipients. Other mutations affected conjugation when present in donors or recipients. Most of the genes identified are known or predicted to affect the cell envelope. Several encode enzymes involved in phospholipid biosynthesis and one encodes a homolog of penicillin binding proteins. Two of the genes identified also affected conjugation of Tn916, indicating that their roles in conjugation may be general. We did not identify any genes in recipients that were essential for ICEBs1 conjugation, indicating that if there are such genes, then these are either essential for cell growth or redundant. Our results indicate that acquisition of ICEBs1, and perhaps other conjugative elements, is robust and not easily avoided by mutation and that several membrane-related functions affect the efficiency of conjugation. PMID:25069588

  18. Strain ŽP - the first bacterial conjugation-based "kill"-"anti-kill" antimicrobial system.

    Science.gov (United States)

    Starčič Erjavec, Marjanca; Petkovšek, Živa; Kuznetsova, Marina V; Maslennikova, Irina L; Žgur-Bertok, Darja

    2015-11-01

    As multidrug resistant bacteria pose one of the greatest risks to human health new alternative antibacterial agents are urgently needed. One possible mechanism that can be used as an alternative to traditional antibiotic therapy is transfer of killing agents via conjugation. Our work was aimed at providing a proof of principle that conjugation-based antimicrobial systems are possible. We constructed a bacterial conjugation-based "kill"-"anti-kill" antimicrobial system employing the well known Escherichia coli probiotic strain Nissle 1917 genetically modified to harbor a conjugative plasmid carrying the "kill" gene (colicin ColE7 activity gene) and a chromosomally encoded "anti-kill" gene (ColE7 immunity gene). The constructed strain acts as a donor in conjugal transfer and its efficiency was tested in several types of conjugal assays. Our results clearly demonstrate that conjugation-based antimicrobial systems can be highly efficient. Copyright © 2015. Published by Elsevier Inc.

  19. Critical Components of the Conjugation Machinery of the Integrative and Conjugative Element ICEBs1 of Bacillus subtilis.

    Science.gov (United States)

    Leonetti, Cori T; Hamada, Matt A; Laurer, Stephanie J; Broulidakis, Matthew P; Swerdlow, Kyle J; Lee, Catherine A; Grossman, Alan D; Berkmen, Melanie B

    2015-08-01

    Conjugation, or mating, plays a profound role in bacterial evolution by spreading genes that allow bacteria to adapt to and colonize new niches. ICEBs1, an integrative and conjugative element of Bacillus subtilis, can transfer itself and mobilize resident plasmids. DNA transfer is mediated by a type IV secretion system (T4SS). Characterized components of the ICEBs1 T4SS include the conserved VirB4-like ATPase ConE, the bifunctional cell wall hydrolase CwlT, and the presumed VirD4-like coupling protein ConQ. A fusion of ConE to green fluorescent protein (GFP) localizes to the membrane preferentially at the cell poles. One or more ICEBs1 proteins are required for ConE's localization at the membrane, as ConE lacks predicted transmembrane segments and ConE-GFP is found dispersed throughout the cytoplasm in cells lacking ICEBs1. Here, we analyzed five ICEBs1 genes to determine if they are required for DNA transfer and/or ConE-GFP localization. We found that conB, conC, conD, and conG, but not yddF, are required for both ICEBs1 transfer and plasmid mobilization. All four required genes encode predicted integral membrane proteins. conB and, to some extent, conD were required for localization of ConE-GFP to the membrane. Using an adenylate cyclase-based bacterial two-hybrid system, we found that ConE interacts with ConB. We propose a model in which the ICEBs1 conjugation machinery is composed of ConB, ConC, ConD, ConE, ConG, CwlT, ConQ, and possibly other ICEBs1 proteins, and that ConB interacts with ConE, helping to recruit and/or maintain ConE at the membrane. Conjugation is a major form of horizontal gene transfer and has played a profound role in bacterial evolution by moving genes, including those involved in antibiotic resistance, metabolism, symbiosis, and infectious disease. During conjugation, DNA is transferred from cell to cell through the conjugation machinery, a type of secretion system. Relatively little is known about the conjugation machinery of Gram

  20. Synthesis and anti-angiogenic effect of conjugates between serum albumin and non-steroidal anti-inflammatory drugs

    DEFF Research Database (Denmark)

    Kjaer, B; Struve, C; Friis, T

    2010-01-01

    of investigating the anti-angiogenic efficiency of NSAID-HSA conjugates in vitro, three NSAIDs, aspirin, ibuprofen, and naproxen were conjugated to HSA using different concentrations of their N-hydroxysuccinimide esters. Conjugation ratios from 10 to 50 were achieved and the conjugates retained a growth inhibitory...

  1. Water-soluble luminescent quantum dots and biomolecular conjugates thereof and related compositions and method of use

    Science.gov (United States)

    Nie, Shuming; Chan, Warren C. W.; Emory, Steven R.

    2002-01-01

    The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.

  2. Water-soluble luminescent quantum dots and biomolecular conjugates thereof and related compositions and methods of use

    Science.gov (United States)

    Nie, Shuming; Chan, Warren C. W.; Emory, Stephen

    2007-03-20

    The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.

  3. Conjugative plasmids: Vessels of the communal gene pool

    DEFF Research Database (Denmark)

    Norman, Anders; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    available within that environment. Here we use the term supergenome to describe the set of all genes that a prokaryotic ‘individual' can draw on within a particular environmental setting. Conjugative plasmids can be considered particularly successful entities within the communal pool, which have enabled HGT...... over large taxonomic distances. These plasmids are collections of discrete regions of genes that function as ‘backbone modules' to undertake different aspects of overall plasmid maintenance and propagation. Conjugative plasmids often carry suites of ‘accessory elements' that contribute adaptive traits...... to the hosts and, potentially, other resident prokaryotes within specific environmental niches. Insight into the evolution of plasmid modules therefore contributes to our knowledge of gene dissemination and evolution within prokaryotic communities. This communal pool provides the prokaryotes with an important...

  4. Tools to Study SUMO Conjugation in Caenorhabditis elegans.

    Science.gov (United States)

    Pelisch, Federico; Hay, Ronald T

    2016-01-01

    The cell biology of sumoylation has mostly been studied using transformed cultured cells and yeast. In recent years, genetic analysis has demonstrated important roles for sumoylation in the biology of C. elegans. Here, we expand the existing set of tools making it possible to address the role of sumoylation in the nematode C. elegans using a combination of genetics, imaging, and biochemistry. Most importantly, the dynamics of SUMO conjugation and deconjugation can be followed very precisely both in space and time within living worms. Additionally, the biochemistry of SUMO conjugation and deconjugation can be addressed using recombinant purified components of the C. elegans sumoylation machinery, including E3 ligases and SUMO proteases. These tools and reagents will be useful to gain insights into the biological role of SUMO in the context of a multicellular organism.

  5. Conjugated Molecules for the Smart Filtering of Intense Radiations

    Directory of Open Access Journals (Sweden)

    Danilo Dini

    2003-04-01

    Full Text Available Abstract: The practical realization of smart optical filters, i.e. devices which change their optical transmission in a suitable way to keep a working state for a general light sensitive element , can involve the use of conjugated molecules whose light absorption properties are light- intensity dependent (nonlinear optical effect. The verification of optical limiting displayed by some particular conjugated molecules, e.g. phthalocyanines, is quite noteworthy and can be successfully exploited for the realization of such smart optical devices. In the present contribution the analysis of the relevant molecular feature of a phthalocyanine are analyzed with the aim of determining useful correlations between optical limiting performance and phthalocyanine chemical structure. In particular , the electronic nature of the substituent is considered as a key factor for the explanation of some observed optical limiting trends.

  6. Conjugate Shear Fractures at 'Ki Corona,' Southeast Parga Chasma, Venus

    Science.gov (United States)

    Willis, J. J.; Hansen, V. L.

    1996-03-01

    Brittle tensile failure of Venus' surface is evident in many tectonic regimes, including as extension fractures associated with caldera collapse, radial and concentric fractures of coronae, fractures normal to folds, and fracture belts. However, evidence of brittle shear failure has been described at only two localities_intersecting fractures oblique to wrinkle ridges in Lavinia Planitia were interpreted as conjugate shear fractures by Watters, and en echelon fractures in Guinevere Planitia record dominant extension. but with a component of shear. We confirm these earlier interpretations, and recognize the widespread nature of conjugate shear fractures across the Venus surface, identifying examples at over 100 locations in varied tectonic regimes, including coronae, wrinkle-ridged plains, and fracture belts. However, we focus here on fracture and fold relations at "Ki Corona" (46.8 degrees S, 302.5 degrees E), and their implications toward corona evolution.

  7. [The profile of female victims of conjugal violence].

    Science.gov (United States)

    Vasseur, Philippe

    2004-12-18

    To define the profile of female victims of conjugal violence examined in the Legal Medicine emergency unit of the Hotel-Dieu hospital in Paris. A self-administered questionnaire with 15 questions was distributed to 100 victims. The 100 victims replied: 86 cases of violence took place usually in the home, 78 episodes of violence were multiple and complaints were rarely lodged after the first episodes. Mental and sexual violence were severe and unrecognized. Eighty women interviewed suffered from mental violence. In 43 cases, alcohol played a determining role in the onset of such violence. Female victims of conjugal violence do not have a specific profile. The law of silence persists, but the increase in the number of complaints from North African and African women is encouraging for the future.

  8. Photon Harvesting in Conjugated Polymer-Based Functional Nanoparticles.

    Science.gov (United States)

    Jana, Bikash; Ghosh, Arnab; Patra, Amitava

    2017-09-21

    The design of new generation light-harvesting systems based on conjugated polymer nanoparticles (PNPs) is an emerging field of research to convert solar energy into renewable energy. In this Perspective, we focus on the understanding of the light harvesting processes like exciton dynamics, energy transfer, antenna effect, charge carrier dynamics, and other related processes of conjugated polymer-based functional nanomaterials. Spectroscopic investigations unveil the rotational dynamics of the dye molecules inside of PNPs and exciton dynamics of the self-assembled structures. A detailed understanding of the cascade energy transfer for white light and singlet oxygen generation in multiple fluorophores containing a PNP system by time-resolved spectroscopy is highlighted. Finally, ultrafast spectroscopic investigations provide direct insight into the impacts of electron and hole transfer at the interface in the hybrid materials for photocatalysis and photocurrent generation to construct efficient light-harvesting systems.

  9. Optimised deconjugation of androgenic steroid conjugates in bovine urine

    DEFF Research Database (Denmark)

    Pedersen, Mikael; Frandsen, Henrik Lauritz; Andersen, Jens Hinge

    2017-01-01

    and glucuronidase resulting in free steroids in the extract. It is well known that some sulphates are not deconjugated using aryl sulphatase; instead, for example, solvolysis can be used for deconjugation of these aliphatic sulphates. The effectiveness of solvolysis on androgenic steroid sulphates was tested...... with selected aliphatic steroid sulphates (boldenone sulphate, nortestosteron sulphate and testosterone sulphate), and the method was validated for analysis of androgenic steroids in bovine urine using free steroids, steroid sulphates and steroid glucuronides as standards. Glucuronidase and sulphuric acid......After administration of steroids to animals the steroids are partially metabolised in the liver and kidney to phase 2 metabolites, i.e., glucuronic acid or sulphate conjugates. During analysis these conjugated metabolites are normally deconjugated enzymatically with aryl sulphatase...

  10. Conjugate schema and basis representation of crossover and mutation operators.

    Science.gov (United States)

    Kazadi, S T

    1998-01-01

    In genetic search algorithms and optimization routines, the representation of the mutation and crossover operators are typically defaulted to the canonical basis. We show that this can be influential in the usefulness of the search algorithm. We then pose the question of how to find a basis for which the search algorithm is most useful. The conjugate schema is introduced as a general mathematical construct and is shown to separate a function into smaller dimensional functions whose sum is the original function. It is shown that conjugate schema, when used on a test suite of functions, improves the performance of the search algorithm on 10 out of 12 of these functions. Finally, a rigorous but abbreviated mathematical derivation is given in the appendices.

  11. Conjugate natural convection in a square porous cavity

    Science.gov (United States)

    Baytaş, A. C.; Liaqat, A.; Groşan, T.; Pop, I.

    Steady-state conjugate natural convection in a square cavity filled with a porous medium is studied numerically in this paper. The enclosure consists of two horizontal conductive walls of finite thickness and two vertical walls at different uniform temperatures. The focus is on the role of solid-fluid conductivity ratio, k, on the flow and heat transfer characteristics and the average Nusselt number, , over the vertical hot and cold walls of the cavity for a limited set of particular parameters. It was shown that the interface temperature, θw, along the top of the solid wall decreases with the increase in the wall conductivity k. Also, the values of decreases with the increase of the values of the parameter k. Comparison with known results from the open literature when the wall thickness of the horizontal solid walls is neglected (non-conjugate problem) is excellent.

  12. Mutagenicity of a Glutathione Conjugate of Butadiene Diepoxide

    Science.gov (United States)

    Cho, Sung-Hee; Loecken, Elisabeth M.; Guengerich, F. Peter

    2013-01-01

    The mutagenicity and carcinogenicity of the important commodity chemical 1,3-butadiene are attributed to the epoxide products. We confirmed our previous work showing that expression of rat glutathione (GSH) transferase 5-5 enhances the mutagenicity of butadiene diepoxide in Salmonella typhimurium TA1535. A GSH-butadiene diepoxide was isolated and fully characterized by mass spectrometry and NMR as S-(2-hydroxy-3,4-epoxybutyl)GSH. The conjugate had a t1/2 of 2.6 h (pH 7.4, 37 °C) and was considerably more mutagenic than butadiene diepoxide or monoepoxide in S. typhimurium. We propose that the GSH conjugate may be a major species involved in butadiene genotoxicity, not a detoxication product. PMID:20879737

  13. Exploring the origin of high optical absorption in conjugated polymers

    KAUST Repository

    Vezie, Michelle S.

    2016-05-16

    The specific optical absorption of an organic semiconductor is critical to the performance of organic optoelectronic devices. For example, higher light-harvesting efficiency can lead to higher photocurrent in solar cells that are limited by sub-optimal electrical transport. Here, we compare over 40 conjugated polymers, and find that many different chemical structures share an apparent maximum in their extinction coefficients. However, a diketopyrrolopyrrole-thienothiophene copolymer shows remarkably high optical absorption at relatively low photon energies. By investigating its backbone structure and conformation with measurements and quantum chemical calculations, we find that the high optical absorption can be explained by the high persistence length of the polymer. Accordingly, we demonstrate high absorption in other polymers with high theoretical persistence length. Visible light harvesting may be enhanced in other conjugated polymers through judicious design of the structure.

  14. Non-classical light emission from single conjugated polymers

    Science.gov (United States)

    Hollars, Christopher; Lane, Stephen; Huser, Thomas

    2002-03-01

    Photon-antibunching from single, isolated molecules of collapsed-chain poly[2-methoxy,5-(2’-ethyl-hexyloxy)-p-phenylene-vinylene] (MEH-PPV) has been observed using confocal microscopy techniques. Efficient inter-segment energy transfer in collapsed-chain conjugated polymers leads to emission from an average of only 2-3 active sites on a polymer chain that is composed of hundreds of quasi-chromophores. These few centers consist of the segments with the lowest excitation energy and are supplied by the efficient light-harvesting and energy transfer of the surrounding higher-energy segments. This effect depends on the conformation of the polymer molecules, which is controlled by solvent polarity. These results provide new insight into the controversial photophysics of conjugated polymers and their application in optoelectronic devices.

  15. Truncated Autoinducing Peptide Conjugates Selectively Recognize and Kill Staphylococcus aureus.

    Science.gov (United States)

    Tsuchikama, Kyoji; Shimamoto, Yasuhiro; Anami, Yasuaki

    2017-06-09

    The accessory gene regulator (agr) of Staphylococcus aureus coordinates various pathogenic events and is recognized as a promising therapeutic target for virulence control. S. aureus utilizes autoinducing peptides (AIPs), cyclic-peptide signaling molecules, to mediate the agr system. Despite the high potency of synthetic AIP analogues in agr inhibition, the potential of AIP molecules as a delivery vehicle for antibacterial agents remains unexplored. Herein, we report that truncated AIP scaffolds can be fused with fluorophore and cytotoxic photosensitizer molecules without compromising their high agr inhibitory activity, binding affinity to the receptor AgrC, or cell specificity. Strikingly, a photosensitizer-AIP conjugate exhibited 16-fold greater efficacy in a S. aureus cell-killing assay than a nontargeting analogue. These findings highlight the potential of truncated AIP conjugates as useful chemical tools for in-depth biological studies and as effective anti-S. aureus agents.

  16. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Directory of Open Access Journals (Sweden)

    Gonglin Yuan

    Full Text Available Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1 βk ≥ 0 2 the search direction has the trust region property without the use of any line search method 3 the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  17. Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

    Science.gov (United States)

    Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

    2015-12-16

    To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

  18. Wavelet methods in multi-conjugate adaptive optics

    International Nuclear Information System (INIS)

    Helin, T; Yudytskiy, M

    2013-01-01

    The next generation ground-based telescopes rely heavily on adaptive optics for overcoming the limitation of atmospheric turbulence. In the future adaptive optics modalities, like multi-conjugate adaptive optics (MCAO), atmospheric tomography is the major mathematical and computational challenge. In this severely ill-posed problem, a fast and stable reconstruction algorithm is needed that can take into account many real-life phenomena of telescope imaging. We introduce a novel reconstruction method for the atmospheric tomography problem and demonstrate its performance and flexibility in the context of MCAO. Our method is based on using locality properties of compactly supported wavelets, both in the spatial and frequency domains. The reconstruction in the atmospheric tomography problem is obtained by solving the Bayesian MAP estimator with a conjugate-gradient-based algorithm. An accelerated algorithm with preconditioning is also introduced. Numerical performance is demonstrated on the official end-to-end simulation tool OCTOPUS of European Southern Observatory. (paper)

  19. Quantum dot conjugates in a sub-micrometer fluidic channel

    Science.gov (United States)

    Stavis, Samuel M.; Edel, Joshua B.; Samiee, Kevan T.; Craighead, Harold G.

    2010-04-13

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  20. Diversity and ecology of filamentous green conjugate algae

    OpenAIRE

    Strouhalová, Pavla

    2016-01-01

    Filamentous conjugating algae have a cosmopolitan distribution. They often inhabit fragile freshwater habitats such as temporary hydrated ditches or puddles of melting snow. Occurrence in this environment entails having to deal with extreme conditions. That helps them to variously adaptation and also the formation of resistant stages. Algae belonging to this group have an important role in nature, because they are often the first species that inhabit newly created habitats and consequently al...