title: Mitochondria-targeted Triphenylamine Derivatives Activatable by Two-Photon Excitation for Triggering and Imaging Cell Apoptosis.
abstract: Photodynamic therapy (PDT) leads to cell death by using a combination of a photosensitizer and an external light source for the production of lethal doses of reactive oxygen species (ROS). Since a major limitation of PDT is the poor penetration of UV-visible light in tissues, there is a strong need for organic compounds whose activation is compatible with near-infrared excitation. Triphenylamines (TPAs) are fluorescent compounds, recently shown to efficiently trigger cell death upon visible light irradiation (458 nm), however outside the so-called optical/therapeutic window. Here, we report that TPAs target cytosolic organelles of living cells, mainly mitochondria, triggering a fast apoptosis upon two-photon excitation, thanks to their large two-photon absorption cross-sections in the 760-860 nm range. Direct ROS imaging in the cell context upon multiphoton excitation of TPA and three-color flow cytometric analysis showing phosphatidylserine externalization indicate that TPA photoactivation is primarily related to the mitochondrial apoptotic pathway via ROS production, although significant differences in the time courses of cell death-related events were observed, depending on the compound. TPAs represent a new class of water-soluble organic photosensitizers compatible with direct two-photon excitation, enabling simultaneous multiphoton fluorescence imaging of cell death since a concomitant subcellular TPA re-distribution occurs in apoptotic cells.
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Rahima
authors.initials: R
authors.lastname: Chennoufi
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Houcine
authors.initials: H
authors.lastname: Bougherara
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gagey-Eilstein
authors.affiliation: Chemistry, Modeling and Imaging for Biology, UMR9187-U1196, Institut Curie, Centre universitaire, 91405 Orsay, France.
authors.forename: Blaise
authors.initials: B
authors.lastname: Dumat
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Henry
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Subra
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bury-Moné
authors.affiliation: Chemistry, Modeling and Imaging for Biology, UMR9187-U1196, Institut Curie, Centre universitaire, 91405 Orsay, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Mahuteau-Betzer
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tauc
authors.affiliation: Chemistry, Modeling and Imaging for Biology, UMR9187-U1196, Institut Curie, Centre universitaire, 91405 Orsay, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.affiliation: LBPA, CNRS UMR8113, IDA FR3242, ENS Cachan, Université Paris-Saclay, F-94235 Cachan, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deprez
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008928:Mitochondria / Q000187:drug effects*; D061848:Optical Imaging / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D000814:Aniline Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species