The mechanism of cell death in photodynamic therapy (PDT) can vary significantly depending on the targeted organelle due to the specific interactions between the photosensitizer, light, and oxygen within that cellular location. Different cell death mechanism can indeed play a crucial role in overcoming drug resistance, a major challenge in cancer treatment. By utilizing PDT reagent to target specific organelles, it is possible to bypass some of these resistance mechanisms or induce synergistic effect when different target motions are engaged simultaneously. For this reason, my group has developed various PDT reagents targeting endoplasmic reticulum (ER), mitochondria, lysosome, and plasma membranes and investigate their cell death mechanisms depending on the targeted organelle.
In this presentation, I will introduce molecular design strategy aimed at targeting organelles. Our developed photosensitizers will be presented for efficient reactive oxygen species (ROS) generation even in hypoxia conditions, detailing the cell death mechanism with proteomic analyses and phenomenological observations by ROS, and their in-vivo applications.1-3