Quantitative drug imaging in living cells using advanced Raman imaging microscopy

Intracellular quantitative drug imaging is still at its infancy due to its slow measurement speed and chemical specificity. Although some progress has been made using spontaneous Raman scattering to identify chemicals using principal component analysis (PCA) and other chemometric methods, spontaneous Raman scattering is very slow, and causes damage to live cells since visible laser beam causes phototoxicity. This project will develop a faster and sensitive non destructive method by combining coherent stimulated Raman scattering (SRS) and spontaneous Raman scattering microscope that will enable detailed investigation of drug-target localisation in living cells, and pharmacokinetics of a drug. The measurements will be validated using another routinely used technique such as mass spectrometry. The technique will facilitate early detection of failure of a drug and accelerate assessment of efficacy of drug uptake. Drugs mounted on nanoparticles will also be studied. These conjugate materials are currently under development as enhanced radiosensitisers in the treatment of cancer however imaging techniques of discriminating their exact location and uptake into cells is urgently needed.

The objectives are:

1. to compare various Raman spectroscopies to image drugs within cells and tissue.

2. to assess the use of drug functionalised nanoparticles for improved uptake and localisation.

3. to determine how this relates to improved understanding of drug action and efficacy.

The student will be trained in Raman spectroscopy, imaging of cells, nanoparticle synthesis and functionalization with drugs.