Cell-Metal Nanoparticle Interaction in a Non-Small Cell Lung Cancer Model

Nanomedicine has attracted great interest in the past few decades. The possibility to reduce sizes down to the micro and nanoscale enables a whole new set of physical phenomena that promises to completely change and revolutionize the way of diagnosing and treating patients. Moreover, the advancements in synthesis and fabrication precision allow for more complex nanomedical platforms to treat a variety of diseases. In cancer therapy, the need for highly selective targeted delivery and real time tracking inside the body led to the development of a broad range of nanocarriers, which differ in formulation, shape and mechanisms of action. Among all the possible carriers, gold nanoparticles offer a well established synthesis process, high biocompatibility, particle tunability, and possibility of surface functionalization. In this work, the interaction between gold nanoparticles and a syngeneic murine Non-Small Cell Lung Cancer (NSCLC) model named Lewis Lung Carcinoma (LLC) is studied. Moreover, the synthesis of two different sizes of gold nanoparticles and their modification in stability, cellular uptake and physicochemical properties upon surface modification is investigated. Among several possible functionalization moieties, Bovine Serum Albumin (BSA) has been studied in detail and the highest possible coating concentration achieved without compromising particle stability is reported. The toxicity and treatment efficacy of the synthesized particles alone and in combination with radiation therapy are studied in vitro. Furthermore, different in vivo experiments are presented to evaluate if gold nanoparticles can work as radiosensitizers in radiation therapy and as contrast agent in CT scan. Tumor 3D reconstructions are presented to correlate over time bare and functionalized particle distribution and retention in vivo in a tumor-bearing mouse. The overall aim of the project is to compare different particle sizes, with corresponding different surface modifications to determine the best candidate for the development of a theranostic platform for cancer therapy. In conclusion, a preliminary study for the future combination of gold nanoparticles radiosensitization and immunotherapy to achieve an abscopal effect in secondary and metastatic tumors is shown.