Development of protein loaded polymersomes for therapeutic applications
File(s)
Author(s)
Thanapongpibul, Chalaisorn
Type
Thesis
Abstract
Protein therapeutics have emerged as a crucial strategy for treating numerous diseases, including cancers and immunological disorders. However, the effectiveness of these therapeutics is often limited by in vivo instability, immunogenicity, and biological barriers. In response to these challenges, polymeric vesicles (polymersomes) have been recognized as promising nanocarriers to enhance the therapeutic effectiveness of proteins. While several physical self-assembly methods for fabricating protein-loaded polymersomes exist, a notable technique is the Polymerization-Induced Self-Assembly (PISA) method, which efficiently encapsulates proteins within the aqueous lumen of the polymersome structure. Importantly, these polymersomes with loaded proteins can be modified as stimuli-responsive systems, enabling controlled release of the protein cargo. This research project aims to develop the synthesis of stimuli-responsive polymersomes loaded with proteins through PISA. A microliter-scale (10 µL) synthetic platform, utilizing a photoinitiated RAFT-mediated PISA (Photo-PISA), was developed specifically for producing protein-loaded pH-responsive polymersomes. This platform offers several advantages such as reduced material consumption and enabling parallel reactions on a benchtop or in multiwell plates. Furthermore, a proof-of-concept is introduced, demonstrating the utilization of intracellular delivery abilities by releasing the loaded cargo upon acidification within the endolysosomal compartments. The study showed that the acidic environment within these compartments played a crucial role in facilitating the release mechanism, allowing the protein cargo to escape into the cytosol. One potential application presented is to facilitate antigen processing and presentation in immune cells, emphasizing their significance in immune modulation, therapeutic approaches. Finally, inspired by natural cellular behavior, this thesis introduces initial works towards cell membrane-coated polymersomes, which show promise for potential biomedical applications and highlight the synergy of biotechnology, polymer science, and cellular mimicry. Overall, this comprehensive research aims to advance the field of protein delivery systems, addressing current limitations and facilitating the exploration of multifaceted applications in the field of biomedicine.
Version
Open Access
Date Issued
2024-01-14
Date Awarded
2024-04-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Stevens, Prof. Molly
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)