Correlative Nano-Characterisation for Prostate Cancer

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Progression of prostate cancer into a metatastic state is postulated to be via exomes, whereby exosomes act to modulate tissues of the body to prepare them to receive and support cancer cell growth. However, addressing this hypothesis has proven challenging as there are many forms of extracellular vesicles of similar size (<150nm) and when isolating extracellular vesicles experimentally at heterogenous population which includes exosomes is collected. Therefore, determination of an enriched exosome fraction prior to experimentation is essential, this requires structural analysis (via cryoTEM) as well as compositional analysis. Through our recent preliminary studies, we can now correlate fluorescently-tagged exosomes optically with structural scanning via cryoTEM. Whilst providing significant structural information, we would like to expand this technique to provide a full compositional analysis at the single exosomes level, this is the first aim of the project. The second aim is to determine the entrance into tissues the exosomes take. This requires a mechanistic and biophysical understanding that is currently lacking. This project will test a selection of different novel workflow methods based around UoN's new cryogenic preparation facility including a plethora of untried correlative workflows to achieve the scientific goals. The project is underpinned by the latest £1.5M strategic equipment award in the Microscale and Nanoscale Research Centre that provides a corelative bridge to combine structural, functional and compositional information on the nanoscale.