Generation, storage and delivery of singlet oxygen by a multifunctional agent
Photodynamic therapy (PDT) relies on thephoto sensitized generation of sin- glet oxygen (by consuming dissolved oxygen) within tumortissues whose oxygen level is already low enough to make this treatment self-limiting. In certain ap- plications, hypoxia induced by photosensitizer is minimized by introducing light intermittently (fractionalPDT) in order to allow time for the replenishment of cellular oxygen, resulting in more effective treatment. In this particular study, we demonstrated that a photosensitizer with an attached 2-pyridone module to halogenated di-styryl BODIPY would be useful in fractional PDT. Upon illumi- nation of photosensitizer (PYR) with a light at specific wavelength in therapeutic window the endoperoxide of 2-pyridone isgenerated along with singlet oxygen. During the time required for replenishment of cellular oxygen the endoperoxide undergoes cycloreversion to produce singlet oxygen, regenerating the2-pyridonemoiety. Such mechanism enables continuation of photodynamic process in the dark, resulting improved fractional photodynamic thearpy drug validated by cell culture studies in vitro.