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Biocompatible glyconanomaterials based on HPMA-copolymer for specific targeting of galectin-3
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SYSNO ASEP 0496863 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Biocompatible 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, ORCIDArticle number 73 Source Title Journal of Nanobiotechnology . - : BioMed Central
Roč. 16, SEP 20 (2018)Number of pages 16 s. Language eng - English Country GB - United Kingdom Keywords Carbohydrate ; ELISA ; Galectin-3 Subject RIV EI - Biotechnology ; Bionics OECD category Microbiology Subject RIV - cooperation Institute of Macromolecular Chemistry - Macromolecular Chemistry R&D Projects GA17-13721S 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 support MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013 UT WOS 000445211800001 EID SCOPUS 85055135018 DOI 10.1186/s12951-018-0399-1 Annotation Background: 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.Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2019
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