NOVEL FLUORESCENT PROBES FOR THE INVESTIGATION OF PLATINUM-BASED ANTICANCER COMPLEXES AND REACTIVE OXYGEN/NITROGEN SPECIES IN CELLS

Abstract

Platinum(IV) prodrug strategy has provided an excellent alternative to overcoming drawbacks associated with conventional platinum(II) drug therapy. Many platinum(IV) complexes have since been developed but there is still much unknown surrounding how this new class of platinum drugs are processed at the cellular level. Current approaches to study platinum compounds such as elemental techniques and fluorescence-tagging have their limitations. The use of exogenous platinum-selective fluorescent sensors could potentially help to overcome challenges associated with these methodologies. In this thesis, we judiciously developed two classes of fluorescent probes, namely intensity-based and ratiometric, to investigate platinum anticancer complexes in cells. The ratiometric sensors were applied to study the intracellular reduction of platinum(IV) prodrug complexes. In addition, the correlation between the amount of active platinum(II) species available after intracellular reduction of platinum(IV) complexes to their cytotoxicity and the role glutathione plays in the reduction of platinum(IV) complexes were also investigated using fluorescence microscopy.