Modifed Silica Nanoparticles for Biomedical Applications

Abstract

Nanoparticles have been extensively explored for biomedical applications primarily due to their nanoscale dimensions that allow them to cross biological membranes and to interact with cells and cellular components. The use of well defined inorganic nanoparticles lacks the necessary functionality to be useful in a wide range of applications, especially those in biology and medicine. As such, in order to overcome these limitations, surface modifications of nanoparticles allows tuning of the interfacial properties such as hydrophilicity, binding and adsorption of molecules and proteins, and cell adhesion - that can be desirable in biomedical applications. Presented here are silica nanoparticles modified with a shell layer of well-defined, high-density polymer brushes generated by surface initiated reversible addition-fragmentation chain transfer polymerization (SI-RAFT). The grafting-from technique adopted in this work allows for significantly higher polymer brush densities as compared to a grafting-to approach. With the ability to extend polymer ligands to desired lengths as well as introducing multivalency to these particles, this design approach enables the fine tuning of particle properties to suit an array of biological applications. The work described in this thesis highlights the versatility of SI-RAFT to synthesize hydrophilic biocompatible polymers to extend the functionalities of nanoparticles through mutivalent effects and improved colloidal stability. The introduction of functional charged polymer brushes is described to afford nanoparticles with antibacterial properties and improve chemokine binding interactions. The thesis also describes the expansion of the types of molecules that can be conjugated to nanoparticles and the use of underutilized reactions, e.g. native chemical ligation (NCL) in order to do so. Specifically, the use of the NCL reaction is described as a novel strategy to post modify hybrid particles with peptides. Finally, with a view to contributing to the development of SI-RAFT polymerization, this thesis includes the optimization of direct SI-RAFT polymerization on colloidal systems to negate the use of sacrificial RAFT agents and allow for efficient synthesis of SI-RAFT modified nanoparticles.