Advances in Living Crystallisation-Driven Self-Assembly
: Towards Biological Applications of Uniform 1D and 2D Polymer-Based Micelles with Controlled Dimensions

  • Horatio He

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Nano- to micro-scale (10-9-10-6 m) objects abundant in nature such as the enzymes in biological processes and cells in tissues exhibit many distinctive functionalities. Most of these natural species possess hierarchical structures and are created, at least in part, via a bottom-up strategy termed self-assembly. It is a challenge for synthetic chemists to achieve assemblies with complex hierarchy and precise control in each tier by the traditional top-down method in manufacturing. However, applying a bottom-up approach mimicking self-assembly in nature to synthetic chemistry could assist in the fabrication of new materials with novel structures and properties. For example, this is achieved with block copolymer (BCP) self-assembly whereby microphase segregation of chemically immiscible polymer blocks occurs. In solution, amphiphilic BCPs have been shown to exhibit self-organization behaviour via a variety of non-covalent interactions to afford micelles with a diverse range of morphologies on the nanoscale. Only recently, unprecedented control over BCP micelle morphologies and dimensions have been shown with BCPs containing a crystalline core forming block. By using a seeded-growth method, both one- and two-dimensional (1D and 2D) micelles and complex supermicelles have been fabricated with precisely controlled sizes via a process termed living crystallisation driven self assembly (CDSA). The work in this thesis presents an extension of the living CDSA strategies to BCPs with a degradable organic core-forming block and explores the potential applications of well-controlled 1D fibre-like micelles in biomedicine.
Chapter 1 provides a general introduction to the relevant topics surrounding the research presented in this thesis. Nanostructures prepared by self-assembly in nature is first briefly discussed, followed by the principles of BCP self-assembly. Living CDSA will be discussed, focussing on the efficiency in precise control over the structure dimensions in 1D and 2D, as well as the fabrication of functional hierarchical supermicelles. Finally, selected work on 1D fibre-micelle applications in drug delivery systems (DDS) and structures based on poly(L-lactide) (PLLA) are presented.
High aspect ratio structures have been reported to be advantageous in DDS, however fibre-like micelles are difficult to attain morphologically pure and with controlled dimensions. In Chapter 2, uniform fibre-like micelles based on poly(ferrocenyldimethylsilane) (PFS) and polyfluorene (PF) have been  

prepared for cellular uptake investigations. Living CDSA has been extensively studied with PFS-containing BCPs and has led to the formation of a wide range of structures with well-defined dimensions. PF-based nanoparticles have been widely used in bioimaging due to their inherent fluorescent characteristics. Dual-fluorescence and cancer cell targeting PF-based micelles have been prepared and PFS-based fluorescent micelles have been shown to enter HeLa cells in cellular uptake studies.
Biodegradable and biocompatible PLLA are promising materials for applications in DDS. However, the preparation of uniform PLLA-based high aspect ratio structures is challenging. Chapter 3 presents the living CDSA of BCP containing a PLLA core-forming block. The main work focus on the optimization of the preparation of uniform fibre-like micelles with controlled length of PLLA-containing diblock copolymers by employing additional solvent additives. It is proposed that the balance of PLLA chain solvation and intermolecular H-bonding has significant effects on the epitaxial growth of the micelles. Solvent additives have been shown to also optimise the seeded-growth other PLLA-containing diblock copolymers whereby complex block co-micelles can be fabricated.
Chapter 4 expands the micelle morphology and dimension control from 1D to 2D via a charge-terminated PLLA homopolymer and a blend of PLLA homopolymer and diblock copolymer. Complex spatial segmented block co-platelet micelles have been prepared. Functional platelet micelles have been shown to template inorganic nanoparticles. Square scarf-like micelles based on a hybrid of 1D fibre-like micelles and 2D diamond-shaped micelles are obtained by sequentially using PLLA homopolymer and diblock copolymer.
Finally, Chapter 5 summarises the progresses achieved in this thesis which contributes to the understanding of living CDSA of organic crystallizable polymers. The future research directions have been discussed which are geared towards functional nanostructures manufacturing, potential applications in catalysis and biomedicine.
Date of Award7 May 2019
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorCharl F J Faul (Supervisor) & Ian Manners (Supervisor)

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