Synthesis and complex self-assembly of AB and ABC amphiphilic block copolymers with a branched hydrophobic poly(2-oxazoline)

Amphiphilic block copolymers (ABPs) have been the focus of numerous studies thanks to their ability to self-assemble into materials with diverse applications, including drug delivery and nanocatalytic reactors. In order to increase the number of ABPs available and broaden the range of self-assembled structures and increase their morphological complexity, this work describes the synthesis of new families of linear AB and ABC amphiphilic block copolymers with a branched hydrophobic poly(2-oxazoline).
First, we synthetized poly(ethylene oxide)-block-poly(2-(3-ethylheptyl)-2-oxazoline) (PEO-b-PEHOx), a new biocompatible amphiphilic AB diblock copolymer obtained in one step via microwave-assisted polymerization of EHOx using a new nosylated PEO macroinitiator. Kinetics of the polymerization in different solvents was crucial to optimize the synthesis and revealed a controlled, yet fast polymerization of the AB copolymer. Differential scanning calorimetry (DSC) proved that PEO-b-PEHOx shows glass transition temperatures below room temperature, making it suitable for a wide range of self-assembly method, especially in mild and solvent-free conditions. Self-assembly of PEO-b-PEHOx was then performed using film rehydration and solvent switch. In both cases, we were able to show the formation of various complex structures (multi-compartment micelles (MCMs), pseudo-vesicles and yolk/shell nanoparticles) by dynamic and static light scattering (DLS/SLS), transmission electron microscopy (TEM) and cryogenic transmission electron microscopy (Cryo-TEM). Our results show that PEO-b-PEHOx is a potent new AB copolymer due to its unique self-assembly behaviour.
In the second part of this thesis, building upon the synthesis of PEO-b-PEHOx, we leveraged the living nature of the polymerization of oxazolines. Via sequential microwave-assisted polymerization, we synthetized in one-pot poly(ethylene oxide)-block-poly(2-(3-ethylheptyl)-2-oxazoline)-block-poly(2-ethyl-2-oxazoline) (PEO-b-PEHOx-b-PEtOz), a new biocompatible amphiphilic ABC triblock copolymer. Depending on the hydrophilic weight fraction of the copolymers, nanoscopic micelles, worms and polymersomes were formed as well as multicompartment vesicles (MCV). The self-assemblies were thoroughly analysed regarding their size and shape using dynamic and static light scattering, TEM and Cryo-TEM. By varying the ratio of PEO to PEtOz, we were able to drive the asymmetry of the polymersome membranes and proved it by two independent methods, bicinchoninic acid (BCA) assay and 2D-1H-NOESY NMR, which confirmed the presence of a longer PEO block (45 units) and the absence of a shorter PEtOz (less than 32 units) on the outer surface of the polymersomes. Thus, from this new family of ABC triblock copolymers, asymmetric polymersomes with a thin membrane (6-10 nm) can be obtained, justifying a potential future use in biomedical applications with the directed insertion of transmembrane proteins.