title: Far-red fluorescence probe for monitoring singlet oxygen during photodynamic therapy.
abstract: Singlet oxygen ((1)O2), molecular oxygen in the lowest excited state, has a critical role in the cell-killing mechanism of photodynamic therapy (PDT). Although (1)O2 phosphorescence measurement has been mainly used to monitor (1)O2 formation during PDT, its intensity is far insufficient to obtain two-dimensional images of intracellular (1)O2 with the subcellular spatial resolution using the currently available near-IR detector. Here, we propose a new far-red fluorescence probe of (1)O2, namely, Si-DMA, composed of silicon-containing rhodamine and anthracene moieties as a chromophore and a (1)O2 reactive site, respectively. In the presence of (1)O2, fluorescence of Si-DMA increases 17 times due to endoperoxide formation at the anthracene moiety. With the advantage of negligible self-oxidation by photoirradiation (ΦΔ < 0.02) and selective mitochondrial localization, Si-DMA is particularly suitable for imaging (1)O2 during PDT. Among three different intracellular photosensitizers (Sens), Si-DMA could selectively detect the (1)O2 that is generated by 5-aminolevulinic acid-derived protoporphyrin IX, colocalized with Si-DMA in mitochondria. On the other hand, mitochondria-targeted KillerRed and lysosomal porphyrins could not induce fluorescence change of Si-DMA. This surprising selectivity of Si-DMA response depending on the Sens localization and photosensitization mechanism is caused by a limited intracellular (1)O2 diffusion distance (∼300 nm) and negligible generation of (1)O2 by type-I Sens, respectively. For the first time, we successfully visualized (1)O2 generated during PDT with a spatial resolution of a single mitochondrial tubule.
authors: The Institute of Scientific and Industrial Research (SANKEN), Osaka University , Mihogaoka 8-1, Osaka, Ibaraki 567-0047, Japan.
authors: Sooyeon
authors: S
authors: Kim
authors: Takashi
authors: T
authors: Tachikawa
authors: Mamoru
authors: M
authors: Fujitsuka
authors: Tetsuro
authors: T
authors: Majima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D017646:Organosilicon Compounds / Q000737:chemistry*; D010778:Photochemotherapy; D012235:Rhodamines / Q000737:chemistry*; D026082:Singlet Oxygen / Q000032:analysis*
chemical_list: D005456:Fluorescent Dyes; D017646:Organosilicon Compounds; D012235:Rhodamines; C000602266:Si-DMA fluorescent probe; D026082:Singlet Oxygen