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Abstract
The development of polymeric nanoparticles for biomedical applications, such as imaging and drug delivery, has been a flourishing area of research for many years. Self-assembly of amphyphilic block copolymers can easily be achieved in water to produce remarkably homogeneous populations of particles with size ranging from tens to hundreds of nanometers. While polymers with two covalently connected blocks often results in spherical geometries and core-shell internal structure, linear triblock terpolymers can achieve more sophisticated morphologies with elongated shape, rough surface and compartmentalised core. The particle shape greatly influences its interaction with the cell membrane and serum proteins, having access to more complex morphologies can give a better understanding of the requirements in the design of an efficient drug carrier. A segregated core structure can also confer additional features to the nanoparticles. The compartments inside the micelles can solubilise different type of cargo in a similar way as transport proteins like serum albumins. For these reasons it is of great interest to develop a linear triblock terpolymer system that can form stable multicompartment micelles in aqueous solution. In this thesis ABC triblock glycopolymers are synthesised using RAFT polymerisation. The polymers are designed to have a hydrophilic sugar-functionalised block, a hydorphobic low-Tg block and a pH-responsive block. Using a step-wise process the polymers are self-assembled into small spherical micelles with a mixed corona, and successively into more sophisticated aggregates. The stimulus triggering the second step of the assembly is the change in solubility of the pH-responsive block upon adjustment of the acidity of the solution. Due to the chemical incompatibility between the core-forming blocks, segregated domains are formed within the nanoparticle and aggregation between them leads to the formation of superstructures with uncommon morphologies such as patchy spheres and caterpillars. Once a procedure to prepare the micelles has been perfected, their interaction with cells in vitro is investigated. This thesis furthers the understanding of the self-assembly of linear triblock glycopolymers in aqueous solution to improve morphological control and evaluates the applicability of these unconventional polymeric paricles as nanocarriers with a focus on the effect of shape and surface functionality.