Inhibition of HIV Viral Infection by Controlling Ligand Position on the Surface of Gold Nanoparticles using Nanografting

The long term goal of this research is to prevent initial HIV viral infection by controlling the galactosylceramide (GalCer) ligand displayed on the surface of nanoparticles using nanografting. GalCer and GalCer analogs have been studied as possible inhibitors of the initial stages of HIV entry. However, the binding efficiency and affinity between GalCer and gp120 are still quite low. Since HIV Env is arranged as a trimer on the virus surface, multivalency of the GalCer ligand must be presented on the delivery vehicle in order to efficiently interact with all three binding sites. Nanoparticles provide a particularly useful platform for this potential delivery system since they are comparable in size to living cells and can be ligand functionalized for biocompatiblity. The goal of this research is to control ligand position on the surface of nanoparticles to viral envelope proteins. Atomic Force Microscopy (AFM)-based fabrication method offers the possibility of controlling ligand distribution with nanometer precision.;In this thesis, AFM-based nanografting was introduced to produce such nanostructures with nanometer precision. This thesis presents preliminary results consisted of three main chapters; (1) synthesis of gold nanoparticles, (2) preparation of immobilized gold nanoparticles on a flat gold surface, (3) high-resolution imaging and production of nanostructures by AFM. The gold nanoparticles were synthesized by seed-mediated growth method in which the nanoparticles were grown from seeds prepared by citrate reduction method. The resulting nanoparticles were characterized using Scanning Electron Microscopy (SEM). Synthesized gold nanoparticles were then immobilized on a flat gold substrate via dithiol ligand exchange in order to be characterized and nanofabricated by AFM. AFM was utilized as a lithographic tool to produce 1-octadecanethiol ligand nanostructures on the surface as well as image ligand nanostructures in situ. A home-built AFM was used for high-resolution imaging and nanografting of Self-Assembled Monolayers (SAMs).