Immunogenicity of gold nanoshell/silica core nanoplasmonics and photothermal induced-cell death

Abstract

Cancer is one of the three leading causes of death in industrialized nations. Conventional therapies, including surgical removal, chemotherapy, and radiation provide increasingly effective methods for the treatment of various types of cancer. The invasiveness and side effects of these treatment methods can potentially be minimized with new thermal ablation therapies. Gold nanoshell enabled photothermal therapy is one thermal ablation strategy with promising initial evidence as a minimally invasive, simple, multifunctional treatment that can both detect and remove tumors efficiently, and have recently reached the clinical trial stage. In this thesis, we characterize the intracellular damage that occurs during the photothermal ablation of cancer cells with varying treatment parameters, and model the corresponding localized temperature profiles to explain the thermal damage on a local level that occurs to proteins, DNA/RNA, and lipid membranes. In addition, Immunological implications to nanoshell enabled photothermal therapy are addressed. Injection of nanoshells require circulation in the bloodstream and deposition in the tumor through the enhanced permeability and retention(EPR) effect. Nanoshells also accumulate in various organs where detection and processing by immune cells such as macrophages can lead to inflammation. Activation of the inflammasome complex, a signaling pathway in response to particulate sensing is assessed by the quantification of secreted proinflammatory cytokines. Finally, immune responses associated with the sensing and clearance of dying cells following nanoshell enabled photothermal therapy are evaluated for determining the generation of an inflammatory environment in the tumor that would generate an anti-tumor immune response to enhance tumor regression and rechallenge.