Development of Gold/gold Sulfide Nanoparticles for Photoacoustic Imaging and Radiotherapy

Cancer is a complex and challenging health concern that requires a tailored approach to treatment. The type of cancer, its stage at diagnosis, and the patient's overall health all play a role in determining the most appropriate therapy. Surgical resection followed by chemotherapy and/or radiation therapy and an imaging technique may be used to improve the chances of a successful outcome. Theranostics is an innovative approach to healthcare that combines diagnostic and therapeutic functions in a single formulation. This allows for the simultaneous diagnosis and treatment of a disease, as well as the real-time monitoring of the treatment's progress and effectiveness. The use of theranostic agents can streamline the process of disease management and improve patient outcomes. Photoacoustic imaging (PAI) is a novel medical imaging method that produces images by analyzing local optical absorption. It utilizes either endogenous or exogenous chromophores with distinguishable optical absorption characteristics, and provides high-contrast images. If an exogenous contrast agent is chosen that has an optical absorption unlike endogenous tissue chromophores, then there will be minimal interference from background tissue signals. Gold nanoparticles (GNP) are a prime example of an exogenous contrast agent, due to their unique optical properties suitable for photoacoustic imaging. The absorption of light in GNP is greatest when the frequency of incident light is in resonance with their surface plasmon resonance (SPR). This resonance is seen in the UV-vis-NIR spectrum, often resulting in a high absorption peak of GNP. GNP are known to be excellent light-to-heat converters, contrast agents, and radiosensitizers. Gold-gold sulfide nanoparticles (GGS), which are relatively new in the literature, absorb NIR wavelengths and potential candidates for increasing effectiveness in tumor therapy and optical imaging. However, little knowledge of the structure and difficulty of maintaining stability complicates its use in the biomedical field. In the first chapter of this thesis, a simple, one-step, aqueous synthesis of GGS nanoparticles was developed. 3-mercaptopropionic acid/ methoxy poly (ethylene glycol) thiol (GGS-3MPA), branched poly (ethyleneimine)/ methoxy poly (ethylene glycol) thiol (GGS-bPEI), and bovine serum albumin (GGS-BSA) coatings were optimized to keep GGS stable. Absorbance, size and surface potential was followed for a year and no significant change observed. The NIR absorbance of the GGS is controversial in the literature. To understand whether the shape anisotropy or core-shell structure of the particles causes NIR property, shape, and size distribution studied by TEM analysis and the compositional changes along the particles measured by XPS. TEM images showed that the solution of GGS has spherical, triangular, hexagonal, octagonal, and rod-like particles with varying sizes. There was no change in the chemical states of the gold and sulfur along the etched layers of GGS. Further characterization was done by DLS-zeta, FTIR, and XRD measurements. In the second chapter, we evaluated the potential of GGS as an exogenous contrast agent for photo-acoustic microscopy (PAM) in visible and near-infrared regions. First, the photoacoustic signals were obtained from the solution of the nanoparticles. For the photoacoustic evaluation in the NIR range, all three GGS were compared with gold nanorods (GNR), which are known for their high NIR absorbing ability. Stronger signals were obtained with GGS compared to GNR. Depending on the cytotoxicity results 100 µg GGS/mL concentration was used for all in vitro imaging and therapy experiments. For in vitro imaging with PAM, HeLa, MDA-MB-231, and L929 cell lines were used. PAI revealed the uptake performance of the synthesized GGS with different coatings. Strong signals were obtained with a 532 nm laser; however, 800 nm results were weak. Later, the potential of GGS as a radiosensitizer was evaluated. Radiation dose-dependent radiotherapy showed that especially GGS-3MPA and GGS-bPEI can lower the cell viability to 25% with 0.05 Gy, which is a very low dose of radiation beyond expected. These results imply the conclusion that healthy tissues may not be harmed by eliminating all the side effects expected in radiotherapy applications in the future.