title: Intracellular modulation of excited-state dynamics in a chromophore dyad: differential enhancement of photocytotoxicity targeting cancer cells.
abstract: The photosensitized generation of reactive oxygen species, and particularly of singlet oxygen [O2 (a(1) Δg )], is the essence of photodynamic action exploited in photodynamic therapy. The ability to switch singlet oxygen generation on/off would be highly valuable, especially when it is linked to a cancer-related cellular parameter. Building on recent findings related to intersystem crossing efficiency, we designed a dimeric BODIPY dye with reduced symmetry, which is ineffective as a photosensitizer unless it is activated by a reaction with intracellular glutathione (GSH). The reaction alters the properties of both the ground and excited states, consequently enabling the efficient generation of singlet oxygen. Remarkably, the designed photosensitizer can discriminate between different concentrations of GSH in normal and cancer cells and thus remains inefficient as a photosensitizer inside a normal cell while being transformed into a lethal singlet oxygen source in cancer cells. This is the first demonstration of such a difference in the intracellular activity of a photosensitizer.
authors: UNAM-Institute of Material Science and Nanotechnology, Bilkent University, Ankara 06800 (Turkey).
authors: Safacan
authors: S
authors: Kolemen
authors: Murat
authors: M
authors: Işık
authors: Gyoung Mi
authors: GM
authors: Kim
authors: Dabin
authors: D
authors: Kim
authors: Hao
authors: H
authors: Geng
authors: Muhammed
authors: M
authors: Buyuktemiz
authors: Tugce
authors: T
authors: Karatas
authors: Xian-Fu
authors: XF
authors: Zhang
authors: Yavuz
authors: Y
authors: Dede
authors: Juyoung
authors: J
authors: Yoon
authors: Engin U
authors: EU
authors: Akkaya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019281:Dimerization; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008027:Light; D051379:Mice; D018613:Microscopy, Confocal; D008958:Models, Molecular; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011162:Porphobilinogen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D026082:Singlet Oxygen / Q000737:chemistry / Q000378:metabolism*
chemical_list: C538930:3-anilino difluoroboron dipyrromethene; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D011162:Porphobilinogen; D005978:Glutathione
keywords: BODIPY dyes; photochemistry; photodynamic therapy; photosensitizers; singlet oxygen