Developing a molecular level understanding of photodynamic therapy using femtosecond pump-probe spectroscopy

Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and bacterial infections. It is based on the concept that a non-toxic chemical, referred to as a photosensitiser, is localised preferentially in the target site and is then activated by light, usually delivered by fibre-optics, so that there is minimal damage to surrounding healthy tissue. The absorption of light triggers a sequence of photophysical and photochemical processes that generate reactive oxygen species which destroy cancer cells, neovasculature or bacteria.

The choice of photosensitiser, the drug-light time interval, drug dose and light flux can be treated as adjustable parameters, to be optimised for a particular PDT. The objective of this proposal is to develop a detailed understanding of the fundamental photophysics, photochemistry and photobiology of PDT at the molecular level. Such understanding is essential if we are to develop the capability to design efficient photosensitisers for specific treatments from first principles.

This discipline hopping proposal seeks to provide the resources for Helen Fielding, an established physical chemist with expertise in gas-phase spectroscopy and dynamics, to acquire expertise in photodynamic therapy ? from the fundamental photochemistry and photophysics of photosensitisers to the biophysics and technology of photodynamic therapy in the clinic.

The overall scientific objective is to develop a detailed understanding of photodynamic therapy at the molecular level, by probing common photosensitisers from the moment they absorb a photon to the time they create reactive radical and singlet oxygen species for the destruction of cancer cells or bacteria. The aim is that this information can then be used to design more efficient photosensitisers and light-fields, for specific treatments, from first principles.