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Polymersomes for biomedical applications : surface functionalization of silicone-based polymer vesicles

Egli, Stefan. Polymersomes for biomedical applications : surface functionalization of silicone-based polymer vesicles. 2011, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_9612

Abstract

Polymersomes prepared from amphiphilic block copolymers are of great interest for applications in diagnostic and therapeutic medicine. In drug delivery, for instance, cargo-carrying polymersomes that can target and attach to specific cell receptors will lead to greater drug efficacy and to fewer side effects. A key aspect considering such applications is to direct the polymersomes to a specific site in vivo, which requires the conjugation of targeting ligands to the surface of the polymeric self-assemblies. Such conjugation chemistry has in turn to fulfill several aspects comprising reaction selectivity and efficiency, stability of the resulting bond, biocompatibility and traceability.
In this thesis, we present different chemical approaches of surface modification of silicone-based block copolymer vesicles. In a first trial, the covalent attachment of oligonucleotides was performed by specific alkyne-azide click-chemistry conjugation. In a second trial, we introduced a new conjugation chemistry that achieves the criteria mentioned before by simple conjugation of 4-formylbenzoate (4FB) functionalized polymersomes with 6-hydrazinonicotinate acetone hydrazine functionalized proteins and antibodies in aqueous buffer. To prove attachment of biomolecules to polymersomes, HyNic functionalized enhanced yellow fluorescent protein was attached to 4FB functionalized polymersomes, resulting in an average number of 5 eYFP molecules per polymersome. Two different polymersome-antibody conjugates were produced using either antibiotin IgG or trastuzumab. They showed specific targeting toward biotin-patterned surfaces and breast cancer cells.
In addition, a new cationic silicone was synthesized, which assembles in certain aqueous salt solutions exclusively in vesicle structures. Because they form complexes with fluorescently labeled siRNA, such cationic silicone vesicles might be useful transfection agents.
In summary, this thesis might impact the future generations and design of modern drug delivery systems.
Advisors:Meier, Wolfgang Peter
Committee Members:Pfohl, Thomas
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)
Item Type:Thesis
Thesis no:9612
Bibsysno:Link to catalogue
Number of Pages:108 S.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:42
Deposited On:04 Oct 2011 13:56

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