‘Shrink-Wrapping’ nanoscale objects

Abstract

This thesis describes the ‘structural metamorphosis’ of discrete single-chain polymer nanoparticles (SCPNs) – an architecture in which a linear polymer chain is intramolecularly crosslinked – into intermolecularly crosslinked polymer films. It was hypothesized that this process could be exploited for the ‘shrink-wrapping’ of 3D nanoscale objects, whereby SCPNs concentrate themselves onto the surface of the object through complementary non-covalent interactions and then spontaneously crosslink with their neighbouring polymer chains to afford a covalently crosslinked film. With the ambitious goal of ‘shrink-wrapping’ virus-like particles (VLPs) in mind, this thesis developed the concept by ‘wrapping’ nano- and microscale objects of increasing complexity. Chapter 1 proposes a definition for ‘structural metamorphosis’ and describes how this phenomenon could be exploited to drive ‘shrink-wrapping’ of virus-like particles. Chapter 2 explores the ‘shrink-wrapping’ of simian virus 40 and Model System I, where the ‘wrapping’ process is driven by simple electrostatic interactions. Chapter 3 describes Model System II, in which specific carbohydrate-receptor interactions drive the ‘shrink-wrapping’ of protein-functionalized silica micro- and nanoparticles. The success of these investigations is largely owed to the development of a highly hydrophilic aldehyde polymer scaffold that was constructed to circumnavigate issues of non-specific binding between polymers and the particle surface. Chapter 4 reports progress in the ‘shrink-wrapping’ of SV40 viral capsid, describing work towards the synthesis of SCPNs functionalized with the oligosaccharide GM1 – the native ligand of SV40. The ‘shrink-wrapping’ of sensitive biomacromolecular targets such as VLPs requires hydrazone exchange chemistry to operate on a reasonable timescale at physiological pH. Published work in Chapter 5 investigates rateenhancing structural features which lead to rapid hydrazone exchange processes at neutral pH. These findings are anticipated to have important consequences on the development of structurally adaptive polymers, materials, molecular machines, nanoparticles and surfaces, where hydrazone exchange chemistry is commonly exploited to endow these systems with stimuli-responsive behaviour.