Experimental and Theoretical Investigation of Laser Photothermal Therapy for Prostate Cancer Treatment Using Gold Nanorods

Gold-based nanoparticles have gained prominence in recent years for use in clinical applications such as imaging, drug delivery, hyperthermia, and tissue ablation. In laser photothermal therapy using gold nanorods, the challenges are unknown distribution of gold nanorod deposition in tumors and treatment efficacy assessment. This dissertation establishes a streamline process of investigating the thermal effects in laser photothermal therapy. It eventually leads to identifying heating protocols for treating prostatic tumors embedded in tissue. It starts with microCT quantification of gold nanorod distribution in tumors after an intratumoral injection to determine the volumetric heat generation rate induced by laser and enhanced by gold nanorods. In vivo animal experiments are performed to measure intratumoral temperature elevations in PC3 xenograft tumors implanted in mice during laser photothermal therapy. The temperature profile suggests that normal tumor tissue still absorbs some amount of the laser energy without nanorod presence; however, the injected nanorods ensure almost all the laser energy is confined to the targeted tumors. It is sufficient to elevate the tumor temperature above 50�C using only 0.1 cc of a nanorod solution at a low laser irradiance of 1.6 W/cm2 on the tumor surface. The observed uniform deposition of nanorods in the tumors would simplify theoretical simulation of temperature elevations in tumor during laser photothermal therapy. The second part of this dissertation is dedicated to measure tumor shrinkage and to perform histologic analyses after laser irradiation to evaluate whether an administered laser photothermal treatment protocol induces adequate thermal damage to tumors. By average, the tumors shrink to less than 7% of its original volume within 25 days after the heating treatment. The tumors without heating continue to grow and double their sizes within 18 days. The histological analyses also show tumor necrosis events surrounding the tumor center after the heating. However, the extent of thermal damage to the tumor is not uniform throughout. The effects of radiation properties of tumor tissue containing gold nanorods at various concentration levels are then evaluated. A computational algorithm of Monte Carlo method is developed to determine the specific absorption rate (SAR) distribution in a spherical tumor containing gold nanorods at specific concentration. The SAR distribution is utilized as a source term in the Pennes bioheat equation to simulate temperature elevations in a spherical tumor implanted in mice. The radiation properties are then extracted via comparing the theoretically predicted temperature profiles in the tumor to that measured in our previous in vivo experiments. The final part of this study is focused on designing a treatment protocol to induced reasonable thermal damage to a tumor embedded in a prostate model, while protecting its surrounding healthy tissue. Monte Carlo and 3-D finite element computational modeling strategies are utilized to evaluate spatiotemporal temperature elevation distribution and thermal damage regions. This leads to identification of heating protocols to induce 100% damage to the tumor, while resulting in less than 5% damage to the surrounding sensitive prostatic tissue

Experimental and Theoretical Investigation of Laser Photothermal Therapy for Prostate Cancer Treatment Using Gold Nanorods

Gold-based nanoparticles have gained prominence in recent years for use in clinical applications such as imaging, drug delivery, hyperthermia, and tissue ablation. In laser photothermal therapy using gold nanorods, the challenges are unknown distribution of gold nanorod deposition in tumors and treatment efficacy assessment. This dissertation establishes a streamline process of investigating the thermal effects in laser photothermal therapy. It eventually leads to identifying heating protocols for treating prostatic tumors embedded in tissue. It starts with microCT quantification of gold nanorod distribution in tumors after an intratumoral injection to determine the volumetric heat generation rate induced by laser and enhanced by gold nanorods. In vivo animal experiments are performed to measure intratumoral temperature elevations in PC3 xenograft tumors implanted in mice during laser photothermal therapy. The temperature profile suggests that normal tumor tissue still absorbs some amount of the laser energy without nanorod presence; however, the injected nanorods ensure almost all the laser energy is confined to the targeted tumors. It is sufficient to elevate the tumor temperature above 50�C using only 0.1 cc of a nanorod solution at a low laser irradiance of 1.6 W/cm2 on the tumor surface. The observed uniform deposition of nanorods in the tumors would simplify theoretical simulation of temperature elevations in tumor during laser photothermal therapy. The second part of this dissertation is dedicated to measure tumor shrinkage and to perform histologic analyses after laser irradiation to evaluate whether an administered laser photothermal treatment protocol induces adequate thermal damage to tumors. By average, the tumors shrink to less than 7% of its original volume within 25 days after the heating treatment. The tumors without heating continue to grow and double their sizes within 18 days. The histological analyses also show tumor necrosis events surrounding the tumor center after the heating. However, the extent of thermal damage to the tumor is not uniform throughout. The effects of radiation properties of tumor tissue containing gold nanorods at various concentration levels are then evaluated. A computational algorithm of Monte Carlo method is developed to determine the specific absorption rate (SAR) distribution in a spherical tumor containing gold nanorods at specific concentration. The SAR distribution is utilized as a source term in the Pennes bioheat equation to simulate temperature elevations in a spherical tumor implanted in mice. The radiation properties are then extracted via comparing the theoretically predicted temperature profiles in the tumor to that measured in our previous in vivo experiments. The final part of this study is focused on designing a treatment protocol to induced reasonable thermal damage to a tumor embedded in a prostate model, while protecting its surrounding healthy tissue. Monte Carlo and 3-D finite element computational modeling strategies are utilized to evaluate spatiotemporal temperature elevation distribution and thermal damage regions. This leads to identification of heating protocols to induce 100% damage to the tumor, while resulting in less than 5% damage to the surrounding sensitive prostatic tissue

Designing Iron Oxide Nanoparticles for Image Guided Thermal Medicine Applications

This work evaluates MRI relaxation and the specific absorption rate properties of iron oxide nanoparticles (IONPs) as a function of diameter (6-32 nm). We conclude that the ideal IONP diameter for image guided heating applications is dependent on the magnetic field strength of the MRI for the intended application. <br /