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Fucoidan-Mimetic Glycopolymers: Synthesis and Biomedical Applications
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The marine polysaccharide fucoidan has demonstrated several interesting biological properties, for instance being antiviral, anticoagulant, anti-inflammatory, anticancer, and platelet activating. Many of these properties are desirable for various biomedical applications. Yet, there are few reports on fucoidan being used in such applications. The reasons for this are primarily the heterogeneity and low structural reproducibility of fucoidan.

This thesis describes the synthesis of polymers with pendant saccharides bearing the key structural features of fucoidan. These glycopolymers were synthesized via different radical polymerization techniques yielding polymers of different chain lengths and dispersity. These glycopolymers showed antiviral and platelet activating properties similar to those of natural fucoidan, thus making them fucoidan-mimetic glycopolymers. However, compared to fucoidan from natural sources, the fucoidan-mimetic glycopolymers had homogeneous and reproducible structures making them suitable for biomedical applications.

Further studies demonstrated that platelet activation, caused by these glycopolymers, showed dose-response curves almost identical to fucoidan. The platelet activation was induced via intracellular signaling and caused platelet surface changes similar to those of fucoidan. Fucoidan-mimetic glycopolymers can therefore be used as unique biomolecular tools for studying the molecular and cellular responses of human platelets.

Fucoidan-mimetic glycopolymers generally assert their antiviral activity by blocking viral entry to host cells, thus inhibiting spreading of the viral infection but not acting virucidal, i.e. not killing the viruses. Introduction of hydrophobic groups to the polymer’s chain ends improved the antiviral properties significantly and is an important step towards yielding glycopolymers with virucidal properties.

The fucoidan-mimetic glycopolymers were also applied as capping agents when synthesizing gold nanoparticles. These fucoidan-mimetic glycopolymer coated gold nanoparticles showed improved colloidal stability compared to uncapped gold nanoparticles. Furthermore, the nanoparticles also demonstrated selective cytotoxicity against a human colon cancer cell line over fibroblast cells.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. , 91 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1743
National Category
Biochemistry and Molecular Biology Chemical Sciences Polymer Chemistry Immunology in the medical area Organic Chemistry
Identifiers
URN: urn:nbn:se:liu:diva-131093DOI: 10.3384/diss.diva-131093ISBN: 9789176858349 (Print)OAI: oai:DiVA.org:liu-131093DiVA: diva2:963103
Public defence
2016-10-14, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2016-09-08 Created: 2016-09-08 Last updated: 2016-09-08Bibliographically approved
List of papers
1. Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization
Open this publication in new window or tab >>Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization
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2014 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, no 7, 2359-2368 p.Article in journal (Refereed) Published
Abstract [en]

The sulfated marine polysaccharide fucoidan has been reported to have health benefits ranging from antivirus and anticancer properties to modulation of high blood pressure. Hence, they could enhance the biological function of materials for biomedical applications. However, the incorporation of fucoidan into biomaterials has been difficult, possibly due to its complex structure and lack of suitable functional groups for covalent anchoring to biomaterials. We have developed an approach for a rapid synthesis of fucoidanmimetic glycopolymer chains through cyanoxyl-mediated free-radical polymerization, a method suitable for chain-end functionalizing and subsequent linkage to biomaterials. The resulting sulfated and nonsulfated methacrylamido alpha-L-fucoside glycopolymers fucoidan-mimetic properties were studied in HSV-1 infection and platelet activation assays. The sulfated glycopolymer showed similar properties to natural fucoidan in inducing platelet activation and inhibiting HSV-1 binding and entry to cells, thus indicating successful syntheses of fucoidan-mimetic glycopolymers.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2014
National Category
Chemical Sciences Clinical Medicine Physical Sciences
Identifiers
urn:nbn:se:liu:diva-109382 (URN)10.1021/bm5002312 (DOI)000339090500003 ()24813544 (PubMedID)
Available from: 2014-08-15 Created: 2014-08-15 Last updated: 2016-09-08Bibliographically approved
2. Synthesis and anticancer properties of fucoidan-mimetic glycopolymer coated gold nanoparticles
Open this publication in new window or tab >>Synthesis and anticancer properties of fucoidan-mimetic glycopolymer coated gold nanoparticles
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2015 (English)In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 51, no 40, 8532-8535 p.Article in journal (Refereed) Published
Abstract [en]

Gold nanoparticles coated with fucoidan-mimetic glycopolymers were synthesized that displayed good colloidal stability and promising anti-cancer properties. Fucoidan mimetic glycopolymers on their own were nontoxic, while glycopolymer coated gold nanoparticles displayed selective cytotoxicity to human colon cancer cell lines (HCT116) while it was non-toxic to mouse fibroblast cells (NIH3T3).

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2015
National Category
Chemical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-119269 (URN)10.1039/c5cc02387d (DOI)000354043200034 ()25892661 (PubMedID)
Note

Funding Agencies|Swedish Strategic Research StemTherapy

Available from: 2015-06-12 Created: 2015-06-12 Last updated: 2016-09-08

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