title: A Bifunctional Photosensitizer for Enhanced Fractional Photodynamic Therapy: Singlet Oxygen Generation in the Presence and Absence of Light.
abstract: The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro.
authors.affiliation: UNAM-National Nanotechnology Research Center, Bilkent University, 06800, Ankara, Turkey.
authors.forename: Ilke Simsek
authors.initials: IS
authors.lastname: Turan
authors.affiliation: Department of Chemistry, Bilkent University, 06800, Ankara, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Yildiz
authors.affiliation: Department of Chemistry, Bilkent University, 06800, Ankara, Turkey.
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Turksoy
authors.affiliation: Department of Basic Oncology, Hacettepe University, 06100, Ankara, Turkey.
authors.forename: Gurcan
authors.initials: G
authors.lastname: Gunaydin
authors.affiliation: UNAM-National Nanotechnology Research Center, Bilkent University, 06800, Ankara, Turkey. eua@fen.bilkent.edu.tr.|Department of Chemistry, Bilkent University, 06800, Ankara, Turkey. eua@fen.bilkent.edu.tr.
authors.forename: Engin U
authors.identifier: http://orcid.org/0000-0003-4720-7554
authors.initials: EU
authors.lastname: Akkaya
mesh_terms: D008027:Light; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D026082:Singlet Oxygen / Q000737:chemistry*
chemical_list: D017319:Photosensitizing Agents; D026082:Singlet Oxygen
keywords: BODIPY; peroxides; photochemistry; photodynamic therapy; singlet oxygen