Fucoidan-Mimetic Glycopolymers: Synthesis and Biomedical Applications
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1743
Biochemistry and Molecular Biology Chemical Sciences Polymer Chemistry Immunology in the medical area Organic Chemistry
IdentifiersURN: urn:nbn:se:liu:diva-131093DOI: 10.3384/diss.diva-131093ISBN: 9789176858349 (Print)OAI: oai:DiVA.org:liu-131093DiVA: diva2:963103
2016-10-14, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (Swedish)
Johansson, Mats, Professor
Konradsson, Peter, ProfessorGriffith, May, ProfessorPåhlsson, Peter, Professor
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