Brain metastases occur in up to a quarter of all cancer patients following primary malignancy treatment, and the prognosis for these patients is very poor. The treatment of these metastatic tumours is greatly hindered by the presence of the blood brain barrier (BBB) which restricts the overwhelming majority of small molecules from entering the brain. A novel approach to overcome this is to target receptor mediated transport mechanisms present on the endothelial cell membranes, in particular the transferrin receptor. Given their specificity, safety profile and stability, nucleic acid based therapeutics are ideal for this purpose. Numerous studies have demonstrated that, despite theoretical implications of rapid renal clearance, nuclease degradation, and electrostatic repulsion, aptamers are effective agents for delivery of cytotoxic agents An aptamer targeting the transferrin receptor was fused with an aptamer that binds to a cell surface marker on breast cancer cells, the epithelial cell adhesion molecule (EpCAM), enhancing binding affinity of both aptamers while maintaining specificity. Using an in vitro BBB model, the aptamer transcytosed the barrier and targeted only EpCAM positive cells in a co-culture of EpCAM positive and negative cell lines. This aptamer also specifically delivered doxorubicin across the in vitro BBB in a timely manner. In vivo, we confirmed the aptamer’s ability to transcytose the BBB in a healthy mouse model following a single i.v. injection (40 nmol/kg)1, and in an animal model of breast cancer brain metastases. Imaging confirmed that this occurred within 10 minutes of an i.v. injection. Using an animal model of breast cancer brain metastases, we also demonstrated rapid drug uptake only in tumour cells in the brain, sparing healthy brain tissue. Work is ongoing to demonstrate efficacy in a small treatment trial. These promising results demonstrate that through the fusion of two aptamer sequences, a bi-functional aptamer can be generated which has the potential to be developed for the specific treatment of EpCAM positive brain metastases.