Radio-Enhancement of Gold Nanoparticles In Ovo and In Vivo as a Therapeutic for Lung Cancer

Cancer is a major public health problem worldwide and is the second leading cause of death in the United States. The most common causes of cancer death are cancers of the lung, prostate, and colorectum in men and the lung, breast, and colorectum in women. These 4 cancers ac- count for 45 percent of all cancer deaths, with one quarter due to lung cancer. It has previously been suggested that approximately 50 percent of all cancer patients receive radiation as a treatment. In Radio Therapy (RT), ionizing radiation (IR) is delivered to the tumor via an external beam. Exposure to IR causes damage to various cellular components, with the DNA being the most critical target, directly or indirectly via ionization of molecules within the cells, generating a cascade of free radicals. While effective at achieving tumor control, the surrounding normal tissues are also affected by the IR. As a result, the dose of radiation administered must be limited in order to keep normal tissue toxicities at a tolerable level. For This reason the use of radioenhancers has been investigated during the last decades as one of the possibility to be able to lower the general delivered radiation dose and, in particu- lar, gold nanoparticles (GNP) have been the main candidates for this purpose due to the fact that they are inert biocompatible materials and have very low toxicity. This thesis focuses on the demonstration of the radioenhancement capabilities of unfuctionalized GNP on Lewis lung (Lucinferase expressed) cells derived tumors. The work evolves from in vitro to in vivo experi- ments, however, as an alternative to the commonly used mouse model, new alternative model is presented : the chick chorioallantoic membrane (CAM). Being immunode cient, fecundated chicken eggs can host, on their CAM, any type of cells, resulting in an ideal environment for tumor growth due to the presence of a blood vessel network that can aliment the carcinoma. Several preliminary experiments were done in order to optimize the number of cells, the amount of gold nanoparticles and the radiation doses, using IVIS imaging as diagnostic tool to monitor tumor growth/reduction. To validate the results of the In Ovo experiments, similar experi- ments were performed with C657Bl/6 mice. This work is highly relevant as it veri es that the CAM is a robust and e cient model to obtain preliminary data on the synergistic e ect of gold nanoparticles and x-ray radiation. This particular research will translate to lower radiation doses required in the clinic, improving patient outcomes through less invasive treatment, faster recovery, and reduced damage to healthy tissue.