Oxygen is widely acknowledged to play a critical role in photodynamic treatments, which often fail due to hypoxia. Researchers have made significant efforts to ensure an adequate oxygen supply during the illumination phase of PDT. Interestingly, some photosensitizers have been found to remain effective even under hypoxic conditions. The objective of this study was to understand the molecular mechanisms behind this behavior and identify design principles for photosensitizers to overcome hypoxia challenges.
The photophysics and photochemistry of hypoxia-active compounds have been studied by steady-state and time-resolved spectroscopic methods. The anticancer and antibacterial activity has been studied by standard cell phototoxicity assays. Mechanistic insight has been gained by the use of confocal microscopy and reactive oxygen species fluorescence probes.
The optical, excited-state, and redox properties of hypoxia-active photosensitisers have been determined, as well as their anticancer and antimicrobial activity, both under normoxia and hypoxia conditions. Distribution of ROS species has been determined in each case.
The main determinants of photodynamic activity under hypoxia are a strong photoredox capacity and the formation of long-lived intermediates upon photoexcitation.