Catalytic bio-hybrid polymersomes: towards novel biomedical applications

Meyer, Claire. Catalytic bio-hybrid polymersomes: towards novel biomedical applications. 2021, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: https://edoc.unibas.ch/84295/

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Merging synthetic polymers with potent biomolecules is an effective strategy to build hybrid systems that benefit from the best of both worlds. However, the combination of polymers with biomolecules bearing strong appeal for biomedical applications, e.g., enzymes producing therapeutic compounds or detectable signals as diagnostic indicators, is often compromised due to the properties of the polymers not matching the requirements for the incorporation of the said active biomolecules. Hence, bio-hybrid polymer nanosystems have yet to develop their full potential for biomedical applications.
Chapter 1 introduces the concept of mimicking compartmentalization of biological cells by the means of synthetic polymers able to build nanocompartments with a large potential for accommodating various biomolecules. An overview of polymer properties, self-assembly of amphiphilic block-copolymers and polymersome formation techniques, as well as target applications of bio-hybrid nanocompartments is given. Finally, strategies to overcome drawbacks of such hybrid systems are introduced.
Chapter 2 describes the aim of this work which is to set stage for biomedical applications involving innovative catalytic nanocompartments encapsulating enzymes. The targeted applications and adopted strategies to develop different bio-hybrid systems are presented.
Chapter 3 highlights the development of a theranostic polymersome-based super assembly aimed at providing a novel type of treatment for atherosclerosis. Separate imaging and therapeutic nanocompartments were tethered together via hybridizing surface-exposed, complementary DNA strands, to form dual-functional polymersome clusters with simultaneous therapeutic and imaging properties. On one hand, on-site dopamine production was achieved by therapeutic compartments encapsulating active Dopa Decarboxylase (DDC), which are permeabilized by membrane insertion of OmpF porin. On the other hand, imaging compartments containing fluorescent dyes enabled tracking of the complete super-assemblies in parallel to their attachment to epithelial cells. Special emphasis is placed on the modularity of such polymersome clusters, as this system represents a novel platform for future dual-functional systems aiming at other biomedical applications.
Chapter 4 presents a polymersome-based bioluminescent system that is able to produce a strong and long-lasting light signal as is desired for pre-clinical imaging applications. The encapsulation of Gaussia Luciferase (GLuc) within the cavity of polymersomes enabled efficient light production. The diffusion of GLuc substrate thought the membrane-inserted OmpF was exploited to modulate the enzyme kinetics such that the signal turned long-lasting. The applicability of such a system was investigated in vitro in cultured cells and in vivo in a mouse model.
Chapter 5 illustrates how mimicking native organelles can be exploited to provide a novel bio-hybrid system showing cell-photoprotective potential. Melanosome mimics were developed via encapsulation of Tyrosinase together with precursors L-DOPA/Dopamine to form macromolecular melanin/polydopamine (PDA) within the cavity of polymersomes. By enclosing the melanin/PDA production, the polymeric membrane prevents the major pitfalls associated with synthetic melanin/PDA nanoparticles and enables a bio-hybrid system with reduced cytotoxicity and enhanced colloidal stability while UV-absorption properties are preserved.
Finally, the mix and match of strategies employed to build the different bio-hybrid systems, the challenge of balancing the polymer/biomolecules selection with the design and optimization possibilities, and the potential of the resulting bio-hybrid systems to evolve into novel biomedical applications are discussed (chapter 6). Complementary material including additional experimental details (chapter 7), relevant literature (chapter 8), contributor and funding acknowledgment (chapter 9), and supplementary figures (chapter 10) conclude this thesis.
Advisors:Palivan, Cornelia G
Committee Members:Huwyler, Jörg and Nardin, Corinne
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Physikalische Chemie (Palivan)
UniBasel Contributors:Palivan, Cornelia G and Huwyler, Jörg
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14319
Thesis status:Complete
Number of Pages:167
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss143198
edoc DOI:
Last Modified:08 Oct 2021 04:30
Deposited On:07 Oct 2021 10:34

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