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Asialoglycoprotein receptor

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https://www.readbyqxmd.com/read/28755539/simultaneous-inhibition-of-growth-and-metastasis-of-hepatocellular-carcinoma-by-co-delivery-of-ursolic-acid-and-sorafenib-using-lactobionic-acid-modified-and-ph-sensitive-chitosan-conjugated-mesoporous-silica-nanocomplex
#1
Ruirui Zhao, Tao Li, Guirong Zheng, Kai Jiang, Lulu Fan, Jingwei Shao
Co-delivery multiple drugs using nanocarriers has been recognized as a promising strategy for cancer treatment to enhance therapeutic efficacy. In this study, a pH sensitive mesoporous silica nanoparticles (MSN) based controlled release nanoparticles for co-delivery of sorafenib (SO), a multi-tyrosine kinase inhibitor, and ursolic acid (UA), a sensitive agent for SO, was developed, which was decorated with pH sensitive chitosan (CS) and lactobionic acid (LA) targeting to asialoglycoprotein receptor (ASGPR) over-expressing hepatocellar carcinoma cells (denoted as USMNs-CL)...
July 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/28720487/pdms-b-pmoxa-polymersomes-for-hepatocyte-targeting-and-assessment-of-toxicity
#2
Klara Kiene, Susanne H Schenk, Fabiola Porta, Alexandra Ernst, Dominik Witzigmann, Philip Grossen, Jörg Huwyler
Nanoparticles, such as polymersomes, can be directed to the hepatic asialoglycoprotein receptor to achieve targeted drug delivery. In this study, we prepared asialofetuin conjugated polymersomes based on the amphiphilic di-block copolymer poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PDMS-b-PMOXA). They had an average diameter of 150nm and formed monodisperse vesicles. Drug encapsulation and sustained release was monitored using the hydrophilic model compound carboxyfluorescein. Asialoglycoprotein receptor specific uptake by HepG2 cells in vitro was energy dependent and could be competitively inhibited by the free targeting ligand...
July 15, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28718478/gsh-responsive-supramolecular-nanoparticles-constructed-by-%C3%AE-d-galactose-modified-pillar-5-arene-and-camptothecin-prodrug-for-targeted-anticancer-drug-delivery
#3
Xin Liu, Wei Shao, Yanjing Zheng, Chenhao Yao, Luming Peng, Dongmei Zhang, Xiao-Yu Hu, Leyong Wang
Supramolecular construction of a targeted and stimuli-responsive drug delivery system is still a challenging task. Herein, GSH-responsive supramolecular prodrug nanoparticles were constructed by the host-guest complexation between a β-d-galactose-functionalized water-soluble pillar[5]arene (GalP5) and a disulfide bond containing camptothecin prodrug (G). The obtained prodrug nanoparticles were stable under physiological conditions, whereas efficient drug release was triggered in a simulated tumor environment with high GSH concentration...
July 27, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28716912/sialylation-on-o-glycans-protects-platelets-from-clearance-by-liver-kupffer-cells
#4
Yun Li, Jianxin Fu, Yun Ling, Tadayuki Yago, J Michael McDaniel, Jianhua Song, Xia Bai, Yuji Kondo, Yannan Qin, Christopher Hoover, Samuel McGee, Bojing Shao, Zhenghui Liu, Roberto Sonon, Parastoo Azadi, Jamey D Marth, Rodger P McEver, Changgeng Ruan, Lijun Xia
Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1(-/-) ). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from HC C1galt1(-/-) mice show reduced levels of α-2,3-linked sialic acids and increased accumulation in the liver relative to wild-type platelets...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28553105/preparation-of-a-dual-cored-hepatoma-specific-star-glycopolymer-nanogel-via-arm-first-atrp-approach
#5
Shaofeng Lou, Xiuyuan Zhang, Mingming Zhang, Shenglu Ji, Weiwei Wang, Ju Zhang, Chen Li, Deling Kong
A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an "arm-first" atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28520401/identification-of-galnac-conjugated-antisense-oligonucleotide-metabolites-using-an-untargeted-and-generic-approach-based-on-high-resolution-mass-spectrometry
#6
Christophe Husser, Andreas Brink, Manfred Zell, Martina B Müller, Erich Koller, Simone Schadt
Antisense oligonucleotides linked by phosphorothioates are an important class of therapeutics under investigation in various pharmaceutical companies. Antisense oligonucleotides may be coupled to high-affinity ligands (triantennary N-acetyl galactosamine = GalNAc) for hepatocyte-specific asialoglycoprotein receptors (ASGPR) to enhance uptake to hepatocytes and to increase potency. Since disposition and biotransformation of GalNAc-conjugated oligonucleotides is different from unconjugated oligonucleotides, appropriate analytical methods are required to identify main cleavage sites and degradation products of GalNAc conjugated and unconjugated oligonucleotides in target cells...
May 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28483695/augmented-liver-targeting-of-exosomes-by-surface-modification-with-cationized-pullulan
#7
Ryo Tamura, Shinji Uemoto, Yasuhiko Tabata
Exosomes are membrane nanoparticles containing biological substances that are employed as therapeutics in experimental inflammatory models. Surface modification of exosomes for better tissue targetability and enhancement of their therapeutic ability was recently attempted mainly using gene transfection techniques. Here, we show for the first time that the surface modification of exosomes with cationized pullulan, which has the ability to target hepatocyte asialoglycoprotein receptors, can target injured liver and enhance the therapeutic effect of exosomes...
May 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28476999/chondroitin-doxorubicin-nanoparticulate-polyelectrolyte-complex-for-targeted-delivery-to-hepg2-cells
#8
Jaleh Varshosaz, Hojjat Sadeghi Aliabadi, Fereshte Asheghali
Chondroitin (Chn) sulphate composed of N-acetyl galactoseamine units was chosen to target doxorubicin (DOX) to asialoglycoprotein receptors (ASGPRs) overexpressed in HepG2 cells of hepatocellular carcinoma (HCC). Two different ways of targeting the drug to the receptors were compared with each other; (i) by polyelectrolyte complex formation of DOX and Chn (DC), (ii) by loading the drug in gelatin nanoparticles (NPs) and then coating them by Chn. The characteristics of DC complexes were determined by Fourier transform infrared spectroscopy, differential scanning calorimetry and CHN analysis...
March 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/28450423/comparative-pharmacology-of-a-new-recombinant-fsh-expressed-by-a-human-cell-line
#9
Wolfgang Koechling, Daniel Plaksin, Glenn E Croston, Janni V Jeppesen, Kirsten T Macklon, Claus Yding Andersen
Recombinant FSH proteins are important therapeutic agents for the treatment of infertility, including follitropin alfa expressed in Chinese Hamster Ovary (CHO) cells and, more recently, follitropin delta expressed in the human cell line PER.C6. These recombinant FSH proteins have distinct glycosylation, and have distinct pharmacokinetic and pharmacodynamic profiles in women. Comparative experiments demonstrated that follitropin delta and follitropin alfa displayed the same in vitro potency at the human FSH receptor, but varied in their pharmacokinetics in mouse and rat...
July 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28418238/specific-and-differential-binding-of-n-acetylgalactosamine-glycopolymers-to-the-human-macrophage-galactose-lectin-and-asialoglycoprotein-receptor
#10
Joji Tanaka, Anne S Gleinich, Qiang Zhang, Richard Whitfield, Kristian Kempe, David M Haddleton, Thomas P Davis, Sébastien Perrier, Daniel A Mitchell, Paul Wilson
A range of glycopolymers composed of N-acetylgalactosamine were prepared via sequential Cu(I)-mediated polymerization and alkyne-azide click (CuAAC). The resulting polymers were shown, via multichannel surface plasmon resonance, to interact specifically with human macrophage galactose lectin (MGL; CD301) with high affinity (KD = 1.11 μM), but they did not bind to the mannose/fucose-selective human lectin dendritic-cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN; CD209). The effect of sugar ligand valency on the binding (so-called "glycoside cluster effect") of poly(N-acetylgalactosamine) to MGL was investigated by varying first the polymer chain length (DP: 100, 64, 40, 23, 12) and then the architecture (4- and 8-arm star glycopolymers)...
April 18, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28397880/glycoengineering-of-pertuzumab-and-its-impact-on-the-pharmacokinetic-pharmacodynamic-properties
#11
Cheng Luo, Song Chen, Na Xu, Chi Wang, Wen Bo Sai, Wei Zhao, Ying Chun Li, Xiao Jing Hu, Hong Tian, Xiang Dong Gao, Wen Bing Yao
Pertuzumab is an antihuman HER2 antibody developed for HER2 positive breast cancer. Glycosylation profiles are always the important issue for antibody based therapy. Previous findings have suggested the impact of glycosylation profiles on the function of antibodies, like pharmacodynamics, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the roles of fucose and sialic acid in the function of therapeutic antibodies still need further investigation, especially the role of sialic acid in nonfucosylated antibodies...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28352174/octanoyl-galactose-ester-modified-microemulsion-system-self-assembled-by-coix-seed-components-to-enhance-tumor-targeting-and-hepatoma-therapy
#12
Ding Qu, Mingjian Liu, Mengmeng Huang, Lixiang Wang, Yan Chen, Congyan Liu, Yuping Liu
A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28335269/galactosylated-liposomes-for-targeted-co-delivery-of-doxorubicin-vimentin-sirna-to-hepatocellular-carcinoma
#13
Hea Ry Oh, Hyun-Young Jo, James S Park, Dong-Eun Kim, Je-Yoel Cho, Pyung-Hwan Kim, Keun-Sik Kim
The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA...
July 30, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28325278/preclinical-and-clinical-advances-of-galnac-decorated-nucleic-acid-therapeutics
#14
REVIEW
Yuanyu Huang
A main challenge in realizing the full potential of nucleic acid therapeutics is efficient delivery of them into targeted tissues and cells. N-acetylgalactosamine (GalNAc) is a well-defined liver-targeted moiety benefiting from its high affinity with asialoglycoprotein receptor (ASGPR). By conjugating it directly to the oligonucleotides or decorating it to a certain delivery system as a targeting moiety, GalNAc has achieved compelling successes in the development of nucleic acid therapeutics in recent years...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28291743/lactobionic-acid-conjugated-tpgs-nanoparticles-for-enhancing-therapeutic-efficacy-of-etoposide-against-hepatocellular-carcinoma
#15
Altansukh Tsend-Ayush, Xiumei Zhu, Yu Ding, Jianxu Yao, Lifang Yin, Jianping Zhou, Jing Yao
Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC...
May 12, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28267669/cell-targeted-dual-reduction-and-ph-responsive-saccharide-lipoic-acid-modified-poly-l-lysine-and-poly-acrylic-acid-polyionic-complex-nanogels-for-drug-delivery
#16
Su-Chun How, Yu-Fon Chen, Pin-Lun Hsieh, Steven S-S Wang, Jeng-Shiung Jan
A cell-targeted, reduction-/pH-responsive polyionic complex (PIC) nanogel system was developed by simply mixing cationic lactobionolatone/lipoic acid-modified poly(L-lysine) (PLL-g-(Lipo-Lac)) and anionic poly(acrylic acid) (PAA), followed by disulfide cross-linking. The nanogels with sizes smaller than 150nm can be prepared at certain mixing ratio via forming interchain disulfide cross-link and helical PAA/PLL complexes. In vitro drug release study showed that Doxorubicin (Dox) release from the nanogels was significantly enhanced by increasing acidity and/or introducing disulfide cleaving agent...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28230359/efficient-liver-targeting-by-polyvalent-display-of-a-compact-ligand-for-the-asialoglycoprotein-receptor
#17
Carlos A Sanhueza, Michael M Baksh, Benjamin Thuma, Marc D Roy, Sanjay Dutta, Cathy Préville, Boris A Chrunyk, Kevin Beaumont, Robert Dullea, Mark Ammirati, Shenping Liu, David Gebhard, James E Finley, Christopher T Salatto, Amanda King-Ahmad, Ingrid Stock, Karen Atkinson, Benjamin Reidich, Wen Lin, Rajesh Kumar, Meihua Tu, Elnaz Menhaji-Klotz, David A Price, Spiros Liras, M G Finn, Vincent Mascitti
A compact and stable bicyclic bridged ketal was developed as a ligand for the asialoglycoprotein receptor (ASGPR). This compound showed excellent ligand efficiency, and the molecular details of binding were revealed by the first X-ray crystal structures of ligand-bound ASGPR. This analogue was used to make potent di- and trivalent binders of ASGPR. Extensive characterization of the function of these compounds showed rapid ASGPR-dependent cellular uptake in vitro and high levels of liver/plasma selectivity in vivo...
February 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28219253/in-vitro-and-in-vivo-evaluation-of-macromolecular-prodrug-gc-fua-based-nanoparticle-for-hepatocellular-carcinoma-chemotherapy
#18
Can Huang, Na-Mei Li, Pei Gao, Sa Yang, Qian Ning, Wen Huang, Zhi-Ping Li, Peng-Ju Ye, Li Xiang, Dong-Xiu He, Xiang-Wen Tan, Cui-Yun Yu
A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28194629/-68-ga-nota-galactosyl-human-serum-albumin-a-tracer-for-liver-function-imaging-with-improved-stability
#19
Roland Haubner, Andreas M Schmid, Andreas Maurer, Christine Rangger, Llanos Geraldo Roig, Bernd J Pichler, Irene J Virgolini
PURPOSE: Non-invasive techniques allowing quantitative determination of the functional liver mass are of great interest for patient management in a variety of clinical settings. Recently, we presented [(68)Ga]DTPA-GSA to target the hepatic asialoglycoprotein receptor for this purpose. Here, we introduce [(68)Ga]NOTA-GSA to improve metabolic stability of the radiopharmaceutical and compare the imaging properties with [(68)Ga]DTPA-GSA. PROCEDURES: Labeling of the compounds was carried out at room temperature using 1...
February 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28179943/synthesis-of-multi-lactose-appended-%C3%AE-cyclodextrin-and-its-cholesterol-lowering-effects-in-niemann-pick-type-c-disease-like-hepg2-cells
#20
Keiichi Motoyama, Rena Nishiyama, Yuki Maeda, Taishi Higashi, Yoichi Ishitsuka, Yuki Kondo, Tetsumi Irie, Takumi Era, Hidetoshi Arima
Niemann-Pick type C (NPC) disease, characterized by intracellular accumulation of unesterified cholesterol and other lipids owing to defects in two proteins NPC1 and NPC2, causes neurodegeneration and other fatal neurovisceral symptoms. Currently, treatment of NPC involves the use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD is effective in the treatment of hepatosplenomegaly in NPC disease, albeit at a very high dose. One of the methods to reduce the required dose of HP-β-CD for treatment of NPC is to actively targeting hepatocytes with β-cyclodextrin (β-CD)...
2017: Beilstein Journal of Organic Chemistry
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