Investigation of the Radiobiological Effect of Gold Nanoparticle Enhanced Radiation Therapy for Cancer Treatment

Radiation therapy has emerged as one of the most effective weapons to combat cancer in both external beam and brachytherapy geometries. Unlike chemotherapy, which exposes the whole body to one or more anti-cancer medications, radiation therapy utilizes localized treatment planning to target cancerous tissue, with very little damage to nearby healthy tissue. The fundamental issue for radiation therapy pertains to delivering the prescribed dose of radiation to the tumor with fewer side effects to the healthy tissue surrounding it. Several advances in beam shaping and image-guided radiotherapy treatment, have paved the way towards more effective forms of radiation therapy such as advances in the clinical use of the Magnetic Resonance Imaging Guided Linear Accelerator (MRI-LINAC) and 3D conformal radiation therapy to measure the most precise dose and treatment path possible. Despite these technological methods for targeting cancer, at radiation doses high enough to effectively treat cancer, serious side effects can still occur. In recent years, the innovative use of gold nanoparticles to locally enhance the radiation dose has shown promising advances in overcoming the drawbacks found in conventional radiotherapy treatment modalities.1-4 In this thesis, the ultimate goal was to investigate the radiobiological damage caused by gold nanoparticle dose enhancement using clinical radiotherapy techniques. To accomplish this goal, we investigated (1) the nanoparticle-cell interactions between biocompatible gold nanoparticles and C33A cervical cancer cells, and (2) the radiobiological effects which takes place upon irradiation of nanoparticle-treated cells in clinical radiation therapy apparatus. The novel aspects of this project are also distinguished from previous studies on the radiobiological effect of nanoparticle-enhanced radiation therapy. First, the investigation of the cytotoxic effects of functionalized gold nanoparticles using image flow analysis, in terms of viability, apoptosis, and necrosis. Following this, we were able to generate confocal images to identify the scattering effects and cellular uptake of the nanoparticles based on the size, shape, concentration of the gold nanoparticles in cellular medium. Secondly, optimized gold nanoparticle functionalization results were used to treat C33A cervical cancer cells and corresponding Ect1/E6E7 noncancerous cervix cells to determine the radio sensitization effect of high-dose-rate (HDR) Ir-192 brachytherapy treatment following gold nanoparticle dose enhancement. This involved accurate Ir-192 source and customized acrylic apparatus set ups, to optimize homogeneous dose distribution to the gold nanoparticle treated cells for evaluating the microscopic dose enhancement at a cellular level. The key focus of this project is centered on medical physics, radiation oncology, and biomedical engineering.