Application of gold nanorods in cancer theranostics

Abstract

In the UK, oesophagogastric cancer is often diagnosed late resulting in only a third of patients being suitable for definitive treatment. The 5-year survival for oesophageal and gastric cancer is 12% and 17% respectively. Despite the need for early detection there remains an inherent risk of missing cancerous lesions during endoscopy. In this research, the combined theranostic (therapy and diagnostic) potential of gold nanorods in gastrointestinal adenocarcinoma is scrutinised. The aims of this thesis were to assess the viability of applying photothermal therapy in human adenocarcinoma ex vivo tissues, determine their efficiency and safety within a rodent cancer model and to design a practical method for simultaneous imaging and therapy of cancer in vivo. Studies were conducted to establish the optimal gold nanorod concentration and irradiation power required for inducing hyperthermic effects in human and porcine tissues and then evaluate the photothermal effects on ex vivo human oesophageal and gastric adenocarcinoma. Multi-functionalised fluorescent gold nanorods were exposed to human adenocarcinoma cells to test in vitro targeting efficiency using immunohistochemistry and fluorescence microscopy. A theranostic approach developed from in vivo studies is described and shown to be effective in identifying tumours and performing image-guided photothermal therapy. Key principles for successful photothermal therapy are outlined. The theranostic potential offered by functionalised gold nanorods have a place in early and late stage cancers, and can be a valuable adjunct in surgery and endoscopy. Safety considerations of the application of gold nanorods and photothermal therapy are evaluated in vivo. Gold nanorods are appraised to be inherently safe while harbouring excellent translational potential as effective theranostic tools. This work has shown that nanotechnology could now be considered for human gastrointestinal tumours. Providing an alternative means of treatment that is effective, cheap and rapid can incur significant improvements in patient prognosis, cancer treatment and quality of life.