keyword
MENU ▼
Read by QxMD icon Read
search

Asialoglycoprotein receptor

keyword
https://www.readbyqxmd.com/read/28988716/evaluation-of-galnac-sirna-conjugate-activity-in-pre-clinical-animal-models-with-reduced-asialoglycoprotein-receptor-expression
#1
Jennifer L S Willoughby, Amy Chan, Alfica Sehgal, James S Butler, Jayaprakash K Nair, Tim Racie, Svetlana Shulga-Morskaya, Tuyen Nguyen, Kun Qian, Kristina Yucius, Klaus Charisse, Theo J C van Berkel, Muthiah Manoharan, Kallanthottathil G Rajeev, Martin A Maier, Vasant Jadhav, Tracy S Zimmermann
The hepatocyte-specific asialoglycoprotein receptor (ASGPR) is an ideal candidate for targeted drug delivery to the liver due to its high capacity for substrate clearance from circulation together with its well-conserved expression and function across species. The development of GalNAc-siRNA conjugates, in which a synthetic triantennary N-acetylgalactosamine-based ligand is conjugated to chemically modified siRNA, has enabled efficient, ASGPR-mediated delivery to hepatocytes. To investigate the potential impact of variations in receptor expression on the efficiency of GalNAc-siRNA conjugate delivery, we evaluated the pharmacokinetics and pharmacodynamics of GalNAc-siRNA conjugates in multiple pre-clinical models with reduced receptor expression...
September 7, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28987883/galnac-bio-functionalization-of-nanoparticles-assembled-by-electrostatic-interactions-improves-sirna-targeting-to-the-liver
#2
Efrat Korin, Tzlil Bejerano, Smadar Cohen
RNA interference (RNAi) has the potential to reversibly silence any gene with high efficiency and specificity. To fulfill the clinical potential of RNAi, delivery vehicles are required to transport the short interfering RNA (siRNA) to the site of action in the cells of target tissues. Here, we describe the features of novel liver-targeted siRNA nanoparticles (NPs), co-assembled due to the complexation of alginate sulfate (AlgS) with siRNA, mediated by calcium ions bridges (AlgS-Ca(2+)-siRNA NPs) and then bioconjugation of a targeting ligand onto the AlgS upon the NP surface...
October 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28982888/accurate-estimation-of-functional-liver-volume-using-gd-eob-dtpa-mri-compared-to-mdct-99m-tc-spect-fusion-imaging
#3
Yuji Morine, Chinbold Enkhbold, Satoru Imura, Tetsuya Ikemoto, Syuichi Iwahashi, Y U Saito, Shinichiro Yamada, Tohru Utsunomiya, Mitsuo Shimada
BACKGROUND/AIM: We assessed the utility of dynamic magnetic resonance imaging (MRI) with gadoxetate-ethoxybenzyl-diethylenetriamine penta-aceticpenta-acetic acid (Gd-EOB-DTPA) (EOB-MRI) for estimating functional liver volume compared to (99m)Tc-galactosyl albumin single-photon-emission computed tomography ((99m)Tc-GSA SPECT). PATIENTS AND METHODS: Regional functional liver volume (left lateral, medial, right anterior, right posterior) of 58 hepatectomized patients was assessed using EOB-MRI and (99m)Tc-GSA SPECT, and compared to the actual liver volume with MDCT-3D volumetry...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28952928/generation-of-an-asgr1-homozygous-mutant-human-embryonic-stem-cell-line-wae001-a-6-using-crispr-cas9
#4
Yingying Xu, Yuhang Wu, Dongsheng Guo, Ge Gao, Keyu Lai, Fan Yang, Kepin Wang, Han Wu, Liangxue Lai, Jialiang Li, Kecheng Xu, Yin-Xiong Li
The gene asialoglycoprotein receptor 1 (ASGR1) encodes a subunit of the asialoglycoprotein receptor. Here we report the generation of a human embryonic stem cell line WAe001-A-6 harbouring homozygous ASGR1 mutations using CRISPR/Cas9. The mutation involves a 37bp deletion, resulting in a frame shift. The homozygous knockout WA01 cell line maintains a normal karyotype, typical stem cell morphology, pluripotency and differentiation potential in vitro.
July 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28922188/new-insights-into-the-role-of-glycosylation-in-lipoprotein-metabolism
#5
Marjolein A W van den Boogert, Daniel J Rader, Adriaan G Holleboom
PURPOSE OF REVIEW: Human genetics has provided new insights into the role of protein glycosylation in regulating lipoprotein metabolism. Here we review these new developments and discuss the biological insights they provide. RECENT FINDINGS: Case descriptions of patients with congenital defects in N-glycosylation (CDG-I) frequently describe a distinct hypocholesterolemia in these rare multisystem clinical syndromes. Two novel CDGs with disturbed Golgi homeostasis and trafficking defects result in mixed glycosylation disorders, hepatic steatosis and hypercholesterolemia...
September 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28895767/promising-galactose-decorated-biodegradable-poloxamer-188-plga-diblock-copolymer-nanoparticles-of-resibufogenin-for-enhancing-liver-cancer-therapy
#6
Hao Dong, Li Tian, Meng Gao, Hong Xu, Chenghong Zhang, Li Lv, Jianbin Zhang, Changyuan Wang, Yan Tian, Xiaochi Ma
Liver cancer is one of the major diseases affecting human health. Modified drug delivery systems through the asialoglycoprotein receptor, which is highly expressed on the surface of hepatocytes, have become a research focus for the treatment of liver cancer. Resibufogenin (RBG) is a popular traditional Chinese medicine and natural anti-cancer drug that was isolated from Chansu, but its cardiotoxicity and hydrophobicity have limited its clinical applications. Galactosyl-succinyl-poloxamer 188 and galactosyl-succinyl-poloxamer 188-polylactide-co-glycolide (Gal-SP188-PLGA) were synthesized using galactose, P188, and PLGA to achieve active liver-targeting properties...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28876162/capacity-limits-of-asialoglycoprotein-receptor-mediated-liver-targeting
#7
Charlotte Bon, Thomas Hofer, Alain Bousquet-Mélou, Mark R Davies, Ben-Fillippo Krippendorff
The abundant cell surface asialoglycoprotein receptor (ASGPR) is a highly selective receptor found on hepatocytes that potentially can be exploited as a selective shuttle for delivery. Various nucleic acid therapeutics that bind ASGPR are already in clinical development, but this receptor-mediated delivery mechanism can be saturated, which will likely result in reduced selectivity for the liver and therefore increase the likelihood for systemic adverse effects. Therefore, when aiming to utilize this mechanism, it is important to optimize both the administration protocol and the molecular properties...
September 6, 2017: MAbs
https://www.readbyqxmd.com/read/28838233/intraorgan-targeting-of-gold-conjugates-for-precise-liver-cancer-treatment
#8
Yuan-Yue Gao, Huan Chen, Ying-Ying Zhou, Lin-Tao Wang, Yanglong Hou, Xing-Hua Xia, Ya Ding
Intraorgan targeting of chemical drugs at tumor tissues is essential in the treatment of solid tumors that express the same target receptor as normal tissues. Here, asialoglycoprotein receptor (ASGP-R)-targeting paclitaxel-conjugated gold nanoparticles (Gal/PTX-GNPs) are fabricated as a demonstration to realize the precise treatment of liver cancer. The enhanced biological specificity and therapeutic performance of drugs loaded on nanoparticles not only rely on the ligands on carriers for receptor recognition but are also determined by the performance of gold conjugates with designed structure...
September 20, 2017: ACS Applied Materials & Interfaces
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
#9
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)...
October 2017: Biomaterials
https://www.readbyqxmd.com/read/28720487/pdms-b-pmoxa-polymersomes-for-hepatocyte-targeting-and-assessment-of-toxicity
#10
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...
October 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
keyword
keyword
111612
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"