The cellular environment in a solid tumour promotes the growth of cancer cells that have adapted to the unique conditions present in tumours, such as low levels of oxygen (hypoxia). Cells exposed to this harsh environment over time are more migratory, invasive and can also develop both radio and chemo-resistance. Effectively killing cancer cells or inhibiting cell migration within the hypoxic tumour microenvironment is expected to reduce the metastatic potential of the solid tumour. By specifically targeting the hypoxic cells, we aim to reduce the metastatic potential of the solid tumour and provide new therapeutic agents to be used in conjunction with other anti-cancer compounds that target the proliferative cells.
We have developed a 3-dimensional cell culture spheroid model of an avascular colon tumour that develops hypoxic regions that are easily distinguishable by live cell fluorescent microscopy. Several approaches have been developed to target hypoxic areas in the tumour model including: cobalt based hypoxia targeted compounds, peptides that are not taken up by cells until cleaved by a tumour specific enzyme and enhancement of drug diffusion by nanoparticles. We show through a combination of live cell microscopy, fluorescence lifetime imaging and cellular assays, that we can successfully manipulate the physico-chemical properties of the molecule/nanoparticle to enhance drug accumulation within hypoxic areas of the 3D spheroid. The development of hypoxia-targeted compounds represents an alternate and complementary use of chemotherapy which is to target the cancer cells with a high potential to metastasize rather than the most proliferative.