Nature provides fascinating examples of functional materials with hierarchical structures. Nano and microscale materials have been prepared by synthetic approaches via the self-assembly of discrete building blocks with the aim to mimic nature’s materials in complexity and size. The solution-state self-assembly of block copolymers (BCPs) with crystallizable core-forming blocks has enabled access to low curvature morphologies such as 1D and 2D micelles via a spontaneous nucleation method termed crystallization-driven self-assembly (CDSA). Via a seeded growth method known as living CDSA, 1D and 2D micelles of controlled dimensions and low dispersity can easily be prepared. However, due to the challenges associated with the synthesis of high aspect ratio nanoparticles and the low number of noncytotoxic polymers known to undergo CDSA, their use for biomedical applications has been limited. The aim of the work described in this thesis is to develop nanofibers of precise dimensions, with nontoxic materials, for potential biomedical applications such as drug delivery, tissue engineering and materials reinforcement. Chapter 1 describes how nature makes superb functional hierarchical materials that serve as inspiration for the development of synthetic methods for the preparation of nano and microstructures. The principles regarding the solution-state self-assembly of BCPs with amorphous or crystalline core-forming blocks are discussed. The preparation of length-controlled nanostructures, segmented micelles, and supermicelles via living CDSA and micelle self-assembly are presented. An introduction to nanoparticle drug delivery, materials reinforcement, and tissue engineering with emphasis on the development and advantages of high aspect ratio nanofibers is given. Finally, a brief perspective on the development of nanofiber-based therapeutics is provided. Chapter 2 discusses the preparation of coaxial-core core nanofibers from the self-assembly of triBCPs. The nanofiber structure is comprised of a crystalline inner core, an amorphous hydrophobic outer core, and a water-soluble corona-forming block. Encapsulation of a model hydrophobic molecule was achieved by the outer amorphous core. This represents the first example of water-soluble, length-controlled, and low length-dispersity (Ð) nanofibers loaded via non-covalent interactions. In Chapter 2, preliminary studies suggested cargo uptake by diBCP nanofibers may be possible. Chapter 3 focusses on investigating the non-covalent loading of length controlled diBCP nanofibers with a hydrophobic cargo. The effect of the chemical identity and the length of the corona-forming blocks was also studied. Chapter 4 describes the self-assembly of B-A-B triBCPs with crystallizable hydrophobic ‘B’ terminal segments to yield fiber-like micelle networks and their potential applications. Conditions for the preparation of discrete crystalline core flower-like micelles and intermicellar fiber-like networks of crystalline core nanofibers were investigated. For the first time, crystalline core nanofiber networks are reported. Chapter 5 focuses on the proof-of-concept development of water-soluble length-controlled nanofibers with corona-forming blocks capable of targeting specific cancer tissue. Additionally, segmented nanofibers for drug delivery applications were prepared. Finally, the association of curcumin with the nanofiber corona-forming block was briefly investigated. Chapter 6 summarizes the work presented in this thesis which contributes towards the development of length-tunable nanofibers for biomedical applications and outlines future research directions of the work presented. / Graduate / 2023-04-20

Self-assembly is ubiquitous in nature. A diverse range of materials with exceptional properties are accessed from a limited number of sub-units, through controlling structural order on all length-scales. Achieving the same level of control to access functional materials akin to those in nature is a key challenge in chemistry. Self-assembly of block copolymers (BCPs) offers a valuable bottom-up route, governed by non-covalent interactions, to access ordered assemblies on the nanoscale. Anisotropic nanostructures, such as one- and two-dimensional (1D and 2D) micelle morphologies, are of particular interest for various applications including those in biomedicine, catalysis, optoelectronics, and materials engineering. Crystallization-driven self-assembly (CDSA) of BCPs containing a crystallizable core-forming segment presents a robust route to preparing 1D and 2D micelles. Significantly, the use of pre-existing seed micelles in a process termed living CDSA allows access to 1D and 2D nanostructures of controlled size and low size-dispersity. Although CDSA protocols represent powerful tools for the formation controlled 1D and 2D nanostructures, key challenges associated with scale-up of these processes remain. In most cases, increasing the concentration at which living CDSA is performed results in competitive self-nucleation, compromising micelle size-control and dispersity. Living polymerization-induced crystallization-driven self-assembly (PI-CDSA) has been presented as a promising alternative route to accessing scalable 1D micelles. In this case, the polymerization, self-assembly, and seeded growth of a BCP containing a crystallizable core-forming segment occur in situ. However, the scope of living PI-CDSA is currently limited to the use of polyferrocenylsilane (PFS)-based BCPs. Owing to the diverse range of crystalline core chemistries compatible with CDSA protocols, and therefore various promising applications of 1D and 2D micelles, scale-up is essential to facilitate their further investigation and application. The work presented in this thesis focusses on upscaling the preparation and processing of controlled 1D and 2D micelles with a crystalline core. The scalable preparation of low dispersity 2D platelet micelles by living CDSA of a charge-terminated PFS homopolymer with surfactant counteranions is presented in Chapter 2. Here, fundamental insight into the effects of living CDSA concentration on platelet dimensions, structure fidelity, and aggregation behaviour is provided. In Chapter 3, the scope of living PI-CDSA is extended to access scalable length-controlled low dispersity 1D nanofibers containing a biodegradable poly(fluorenetrimethylenecarbonate) (PFTMC) crystalline core. PFTMC-based 1D fibers are of interest for biomedical applications, hence, in this work, it is demonstrated that living PI-CDSA can be used to prepare fibers exhibiting biologically-relevant lengths at scalable concentrations. In Chapter 4, the scalable formation of low dispersity 1D micelles by living CDSA of a PFS-based BCP in a continuous flow setup is explored. Processing of 1D micelles into microfibers using simple, low cost, and high throughput electrospinning techniques is demonstrated in Chapter 5. Finally, Chapter 6 summarises the contribution of this thesis to improving the scalability of CDSA protocols and provides future directions for this work. / Graduate / 2023-04-12