The development of gold nanoparticle conjugates for the intracellular delivery of paclitaxel
Doctor of Philosophy
The following work describes our efforts toward the development of a novel gold nanoparticle (AuNP) system capable of the quantitative intracellular delivery of the known chemotherapeutic, paclitaxel. The synthetic strategy employed here features the covalent grafting of multiple drug molecules to the surface of individual gold nanocrystals measuring 2 nm in diameter. This core-shell approach is advantageous as it allows for structural analysis based on traditional analytical techniques and, therefore, definitive confirmation of chemical structure. Perhaps more importantly, the ability to manufacture such a well-defined delivery system allows one to more accurately quantify the amount of bound drug and ultimately, biological activity. While varying the linker structure results in analogous paclitaxel-AuNP conjugates capable of drug release based on endogenous biological processes, a study of the inherent intracellular behavior of these gold nanoparticles led to the discovery of a specific functionality required for efficient drug dissociation under cellular conditions. In fact, results from cell culture experiments reveal this novel delivery system as having comparable toxicity to that of the parent drug, while demonstrating a marked reduction in systemic toxicity in animal models.