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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F18%3A00496863" target="_blank" >RIV/61388971:_____/18:00496863 - isvavai.cz</a>

Alternative codes found

RIV/61389013:_____/18:00496863

Result on the web

<a href="http://dx.doi.org/10.1186/s12951-018-0399-1" target="_blank" >http://dx.doi.org/10.1186/s12951-018-0399-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12951-018-0399-1" target="_blank" >10.1186/s12951-018-0399-1</a>

Result language

angličtina

Original language name

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

Original language description

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. nResults: 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. nConclusions: 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10606 - Microbiology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Nanobiotechnology

ISSN

1477-3155

e-ISSN

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Volume of the periodical

16

Issue of the periodical within the volume

SEP 20

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

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UT code for WoS article

000445211800001

EID of the result in the Scopus database

2-s2.0-85055135018