Chemical and Biomolecular Engineering - Theses

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Start date: 2000 × End date: 2019 × Subject: drug delivery × Subject: bioconjugate chemistry ×

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    Engineering biomacromolecule-based particles with tunable functionality in biological systems
    SUMA, TOMOYA ( 2016)
    Particles with tailored physicochemical properties have numerous applications in diagnosis, therapy, and management of human diseases. In this context, elucidation of the interactions between biological systems and nanoengineered materials has emerged as an important research discipline, with the ultimate aim of controlling the interactions to achieve desired physiological responses. Biomacromolecules, such as peptides, proteins and polysaccharides, have diverse physiological functions, such as target recognition, signaling, and catalysis, which remain a challenge to mimic by synthetic methods. Biological systems precisely control synthesis, assembly, and disassembly of the biomacromolecules to guide physiological events. Therefore, controlled assembly of biomacromolecules into nano- and microscale particles may offer a promising platform to study bio-nano interactions, and ultimately to engineer functional materials for biomedical applications. However, previous studies have primarily been limited to particles assembled from biomacromolecules with little function. In this thesis, a robust strategy of assembling functional biomacromolecules into particles is developed, through the use of porous particles as sacrificial templates and reversible chemistry integrated into the biomacromolecular network. The advantages of this strategy include simplicity, versatility, tunability of particle morphology, triggered disassembly, and bioactivity that can be triggered in certain biological conditions. Three types of biomacromolecule-based particles were engineered: (1) peptide nanoparticles with proapoptotic activity (Chapter 3), (2) protein particles with pH-triggered recovery of enzymatic activity (Chapter 4), and (3) polysaccharide-based particles that can be targeted to tumour associated macrophages and Escherichia Coli (Chapter 5). These systems are used to demonstrate how the functionality of the particles in biological systems can be tuned using a chemistry and materials science-based approach.