Visualising the intracellular environment during normal cell function and photodynamic therapy using advanced imaging techniques

Lead Research Organisation: Imperial College London
Department Name: Chemistry


Photodynamic Therapy (PDT) is an established method to treat the variety of cancers (particularly lung, head, neck and non-melanoma skin cancer) and for treating the disease known as acute macular degeneration (AMD) which is a main source of legal blindness in old people. It is based on the light activation of the sensitizer molecules preferentially localised in the cancerous tissues, which produce cytotoxic species such as singlet oxygen, which kill surrounding cells in the target areas. For full understanding of PDT mechanism it is crucial to be able to visualise the localisation of both the sensitiser and cytotoxic species within cells. This proposal seeks to use advanced imaging techniques, the combination of fluorescence, Raman and second harmonic generation imaging to visualise individual intracellular events during normal cell function and PDT-induced cell death. We will take advantage of high two-photon absorption (TPA) cross sections of conjugated porphyrin dimers for TPA PDT and TPA intracellular imaging for high image resolution, deeper tissue penetration and precise application of light for the benefit of treatments of diseases such as AMD, where out of focus damage should be minimised. Series of sensitisers would be screened for photophysical properties, cell localisation and PDT action in vitro to reveal the best candidates for in vivo testing. We will combine imaging results for the sensitisers with that of singlet oxygen, the cytotoxic species responsible for cell death, which would provide us with the insight of the PDT mechanism in cellulo. This is an interdisciplinary project involving molecular design, synthesis, photophysics, photochemistry, imaging, spectroscopy and cell biology.


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Description 1. Two-photon Photodynamic Therapy (PDT) utilising conjugated porphyrin dimers was demonstrated in live cells for the first time

2. A new type of fluorescent probes for microscopic viscosity termed molecular rotors were fully photochemically characterised and used for studies of viscosity in live cells

3. We demonstrated that viscosity in hydrophobic organelles in cells is 100x higher than that of water and that the viscosity changes dramatically during PDT in single cells
Exploitation Route Primarily by the academic community, for measuring viscosity in variety of systems of interest to biology, material science and engineering.
Sectors Chemicals,Healthcare

Description Imperial College London
Amount £1,173,882 (GBP)
Funding ID EP/I003983/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom