This research proposal aims to develop smart fluorescent probes to be used as in-situ and real-time diagnostic tools by fibre-based confocal microendoscopy imaging with local administration. The probes will target relevant biomarkers in cancer and infection, and will be generated through a multidisciplinary approach that involves organic chemistry, cell biology, imaging and respiratory medicine. Activatable fluorescent probes are advantageous in that their fluorescent signal is triggered by a target protein, and hence they emit fluorescence ONLY AFTER interaction with the defined target (e.g. enzyme) or environment. This strategy leads to optimum signal-to-noise ratios with increased sensitivity over other optical imaging approaches and enables their use in small concentrations with no systemic administration, hence reducing any potential adverse effects and facilitating the translation to clinical applications. The current proposal will focus on two projects:
1) Enzyme-activatable probes for imaging endoscopically-accesible cancer (initially targeted at lung cancer, but later also applicable to oesophagus and pancreas cancer);
2) Environment-sensitive fluorescent probes for the detection of fungal infection in lungs (i.e. pulmonary aspergillosis).