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Biocompatible glyconanomaterials based on HPMA-copolymer for specific targeting of galectin-3

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    SYSNO ASEP0496863
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleBiocompatible glyconanomaterials based on HPMA-copolymer for specific targeting of galectin-3
    Author(s) Bojarová, Pavla (MBU-M) ORCID
    Tavares, Marina Rodrigues (UMCH-V) ORCID, RID
    Laaf, D. (DE)
    Bumba, Ladislav (MBU-M) RID, ORCID
    Petrásková, Lucie (MBU-M) ORCID
    Konefal, Rafal (UMCH-V) RID, ORCID
    Bláhová, Markéta (UMCH-V) RID, ORCID
    Pelantová, Helena (MBU-M) ORCID, RID
    Elling, L. (DE)
    Etrych, Tomáš (UMCH-V) RID, ORCID
    Chytil, Petr (UMCH-V) RID, ORCID
    Křen, Vladimír (MBU-M) RID, ORCID
    Article number73
    Source TitleJournal of Nanobiotechnology . - : BioMed Central
    Roč. 16, SEP 20 (2018)
    Number of pages16 s.
    Languageeng - English
    CountryGB - United Kingdom
    KeywordsCarbohydrate ; ELISA ; Galectin-3
    Subject RIVEI - Biotechnology ; Bionics
    OECD categoryMicrobiology
    Subject RIV - cooperationInstitute of Macromolecular Chemistry - Macromolecular Chemistry
    R&D ProjectsGA17-13721S GA ČR - Czech Science Foundation (CSF)
    GA18-01163S GA ČR - Czech Science Foundation (CSF)
    NV16-28594A GA MZd - Ministry of Health (MZ)
    LO1507 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    LTC17005 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    LM2015064 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Institutional supportMBU-M - RVO:61388971 ; UMCH-V - RVO:61389013
    UT WOS000445211800001
    EID SCOPUS85055135018
    DOI10.1186/s12951-018-0399-1
    AnnotationBackground: Galectin-3 (Gal-3) is a promising target in cancer therapy with a high therapeutic potential due to its abundant localization within the tumor tissue and its involvement in tumor development and proliferation. Potential clinical application of Gal-3-targeted inhibitors is often complicated by their insufficient selectivity or low biocompatibility. Nanomaterials based on N-(2-hydroxypropyl)methacrylamide (HPMA) nanocarrier are attractive for in vivo application due to their good water solubility and lack of toxicity and immunogenicity. Their conjugation with tailored carbohydrate ligands can yield specific glyconanomaterials applicable for targeting biomedicinally relevant lectins like Gal-3.
    Results: In the present study we describe the synthesis and the structure-affinity relationship study of novel Gal-3-targeted glyconanomaterials, based on hydrophilic HPMA nanocarriers. HPMA nanocarriers decorated with varying amounts of Gal-3 specific epitope GaINA031,461cNAc (LacdiNAc) were analyzed in a competitive ELISA-type assay and their binding kinetics was described by surface plasmon resonance. We showed the impact of various linker types and epitope distribution on the binding affinity to Gal-3.The synthesis of specific functionalized LacdiNAc epitopes was accomplished under the catalysis by mutant beta-N-acetylhexosaminidases. The glycans were conjugated to statistic HPMA copolymer precursors through diverse linkers in a defined pattern and density using Cu(I)-catalyzed azide- alkyne cycloaddition. The resulting water-soluble and structurally flexible synthetic glyconanomaterials exhibited affinity to Gal-3 in low mu M range.
    Conclusions: The results of this study reveal the relation between the linker structure, glycan distribution and the affinity of the glycopolymer nanomaterial to Gal-3.They pave the way to specific biomedicinal glyconanomaterials that target Gal-3 as a therapeutic goal in cancerogenesis and other disorders.
    WorkplaceInstitute of Microbiology
    ContactEliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
    Year of Publishing2019
Number of the records: 1  

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