Development of pH-responsive microgels and nanogels with gold nanoparticles based on the design of particle structure and gel network

Abstract

This thesis presents a study of pH-responsive nanogel (NG) or microgel (MG) based systems, which aimed to achieve improved functionality and gel performance for future biomedical applications. Doubly crosslinked (DX) MGs have already been studied and suggested in the recovery of degenerated intervertebral discs. The next generation of gel could focus on the improvement in therapeutic and diagnostic treatment. In the first study of this thesis, gold nanoparticles (Au NPs) were synthesised to generate the localised surface plasmon resonance (LSPR) property for NGs using core-shell approaches. The colloidal stability of Au NPs relies on the electrostatic repulsion due to a citrate reduction. Therefore, the aggregation of Au NPs is unavoidable for the preparation of DX MGs. This result was observed in the study of poly(ethyl acrylate-methacrylic acid-divinylbenzene) MGs (poly(EA-MAA-DVB) MGs). Precipitation polymerisation is a powerful method to construct a temperature-responsive poly(N-isopropylacrylamide) copolymer shell for Au NPs. However, a functionalisation step is usually required to facilitate shell growth. I evaluated three core-shell approaches and created a new methodology of precipitation polymerisation without using any pre-functionalisation steps. Finally, a well-defined core-shell structure was synthesised by constructing a NG shell of poly(methyl methacrylate-methacrylic acid-ethylene glycol dimethacrylate). Those new core-shell particles had excellent colloidal stability in electrolytes. LSPR properties of the Au NP core-shell dispersion were restorable from salt-triggered sediments or oven-dried solids. The facile methodology of core-shell syntheses allowed the investigation of pH-response and shell thicknesses dependent LSPR properties in the second study. I synthesised five types of acrylic-based core-shell particles with tuneable shell thicknesses. The shell composition was mainly varied by the content of either 2-carboxyethyl acrylate (CEA) or methacrylic acid (MAA). The resultant NG shells were thin and ranged from 2 - 18 nm based on measurements from TEM. All swelling and LSPR properties were recorded and compared for the analysis. LSPR peak wavelengths were strongly dependent on the NG shell thickness. The maximum peak wavelength of core-shell particles achieved 529 nm, which had a 10 nm red-shift compared to the parent Au NPs. The spectral change and near-field map were subsequently provided using finite difference time domain (FDTD) simulations. The experimental data of LSPR properties fitted well with those predictions. The pH-dependent change of LSPR peak wavelengths was also found in a highly swellable MAA-containing core-shell particle. A visible colour transition was observed from pH 6 to pH 11. Importantly, pH-triggered reversible aggregation existed in a CEA-containing core-shell particle. Their thin NG shells provided an effective coupling effect for the Au cores. The internalisation study of HeLa cell culture further proved CEA-containing core-shell particles have the potential in sensing the intracellular pH for future biomedical uses. The mechanical property of DX MGs is not ductile enough to enable a useful investigation of core-shell particles (e.g. a remote probe of gel environments or mechanics). The development of the gel network is also important. Therefore, the last piece of work focused on the generation of new gel using pH-responsive poly(EA-MAA-DVB) MGs. I developed a new methodology by constructing a physical gel network with branched polyethyleneimine (PEI). A complex coacervate was formed due to a strong interaction between anionic MGs and cationic PEI. This polymer/MGs complex coacervate (PMCC) system showed outstanding gel property performance, including super-stretchability, self-healing, super-swellability and strong adhesion. A highly deformable and injectable pre-gel could be transformed to an elastic and stable gel by simply tuning the annealing temperature ( > 37 °C). Moreover, the stiffness of elastic gel can largely increase up to 34 MPa after introducing Ca2+ crosslinking. The work provides the basis for new gels, which could be used to monitor biomechanical properties remotely.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Brian Saunders (Supervisor) & Stephen Edmondson (Supervisor)