Theranostic Gold Nanostars for Combined Magnetic Resonance imaging (MRI) and Photothermal Therapy

Abstract

Cancer remains a leading cause of death, largely due to early detection and therapeutic limitations. Theranostics offers an effective approach to cancer treatment. The combination of magnetic resonance imaging (MRI) and photothermal therapy (PTT) represents a strategy in cancer theranostics, combining high-contrast imaging with localised, light-triggered therapy for enhanced detection of cancer and reduced therapeutic side effects. This thesis presents the design, synthesis, and evaluation of gadolinium (Gd)-functionalised gold nanostars (GNS) as multifunctional platforms for cancer theranostics. It explores how nanostructure morphology and surface chemistry affect MRI contrast, NIR-triggered photothermal therapy, and pH-responsive drug delivery. The first stage of the work investigates the relaxometric behaviour of Gd-functionalised GNS coated with polyethylene glycol (PEG). Two distinct Gd chelates were used, and the resulting nanostructures were characterised for size, composition, and colloidal stability. Relaxivity measurements revealed significantly enhanced MRI contrast compared to the clinical standard Dotarem, with results indicating that surface hydration and chelate local environment are key drivers of relaxivity performance The second stage assesses the photothermal capabilities of the same GNS-PEG-Gd formulations under NIR laser irradiation. Both formulations demonstrated efficient and reproducible heating. In vitro experiments confirmed the biocompatibility of the GNS-PEG-Gd in the absence of irradiation and substantial cell death following laser irradiation, validating their function as photothermal agents. The final stage introduces a multifunctional GNS platform coated with thiolated and hydrazide-modified hyaluronic acid (HA) of two molecular weights. These nanostructures were designed to integrate imaging, PTT, and pH-sensitive doxorubicin (DOX) release. The HA-coated GNS maintained high relaxivity and photothermal performance. While drug release and chemotherapy effects in vitro were modest, the system successfully demonstrated stimulus-responsive behaviour. This thesis contributes to understanding the role of surface chemistry in determining the imaging and therapeutic performance of gold nanostructures, offering a platform for integrated cancer theranostics and future clinical translation.