|Photodynamic therapy (PDT) is a treatment for cancer that involves exposure of tissues to a photosensitizing drug followed by irradiation with light of appropriate wavelength, typically red or near infrared light. USFDA has approved PDT for advanced esophageal and lung cancer. PDT is currently in clinical trials for a number of other cancer types, including cancers of the prostate, head-and-neck, brain, skin, and breast cancer metastatic to skin or spine. PDT requires a photosensitizer,|
non-thermal visible light, and molecular oxygen. Absorption of a photon activates the photosensitizer to an excited singlet state that can then undergo intersystem crossing to the triplet state. The triplet transfers energy to molecular oxygen to generate singlet oxygen, or it undergoes oxidation-reduction reactions to generate other reactive oxygen species (ROS). With adequate oxygen and light intensity, the site of initial photodamage depends on the location of the photosensitizer, generally intracellular membranes, culminating in tumor cell death. Both lipids and proteins can be molecular targets of PDT.
Apoptosis is a common mode of cell death following PDT both in vitro and in vivo, especially for photosensitizers localized to mitochondria. We have shown that PDT with phthalocyanine photosensitizer Pc 4 causes accelerated generation of ROS, cross-linking of mitochondrial proteins, mitochondrial inner membrane permeabilization, depolarization and swelling, release of cytochrome c, and activation of both necrosis and caspase-dependent apoptosis.
Our goal is to further characterize the interactions of damage to ER and lysosomes in promotion of death pathways. Live cell imaging with confocal/multiphoton microscopy is an integral part of the experimental design in this project.