Development of Ligand-Directed Drug-Loaded Liposomes to Target Heterogeneous Tumour Cell Populations in Metastatic Breast Cancer

The tendency for breast cancer cells in the primary tumour to spread to other parts of the body and form new tumours in vital organs, termed metastasis, is the main cause of breast cancer-related mortality. Therapies that target highly metastatic cells have proved successful in the clinic, but the development of therapeutic resistance to these targeted therapies significantly limits clinical efficacy. Therefore, new anticancer therapies that target invasive tumour cells while minimising systemic toxicity are required. The urokinase plasminogen activator receptor (uPAR) is recognised as a biomarker for metastasis in breast cancer. Targeting uPAR in breast cancer can be achieved by attaching plasminogen activator inhibitor-2 (PAI-2) to the surface of drug-loaded liposomes in order to facilitate liposome uptake into uPAR-positive cells. This thesis aimed to develop and evaluate novel uPAR-targeted liposomes containing a potent anti-mitotic cytotoxin, N-alkylisatin (N-AI), for the treatment of metastatic breast cancer.