title: Anticancer phototherapy using activation of E-combretastatins by two-photon-induced isomerization.
abstract: The photoisomerization of relatively nontoxic E-combretastatins to clinically active Z-isomers is shown to occur in solution through both one- and two-photon excitations at 340 and 625 nm, respectively. The photoisomerization is also demonstrated to induce mammalian cell death by a two-photon absorption process at 625 nm. Unlike conventional photodynamic therapy (PDT), the mechanism of photoisomerization is oxygen-independent and active in hypoxic environments such as in tumors. The use of red or near-infrared (NIR) light for two-photon excitation allows greater tissue penetration than conventional UV one-photon excitation. The results provide a baseline for the development of a novel phototherapy that overcomes nondiscriminative systemic toxicity of Z-combretastatins and the limitations of PDT drugs that require the presence of oxygen to promote their activity, with the added benefits of two-photon red or NIR excitation for deeper tissue penetration.
authors.affiliation: Research Complex at Harwell, Central Laser Facility, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0FA, United KingdombUniversity of Salford, Biomedical Research Centre, Salford, Greater Manchester M5 4WT, United Kingdom.
authors.forename: Kathrin M
authors.initials: KM
authors.lastname: Scherer
authors.affiliation: University of Salford, Biomedical Research Centre, Salford, Greater Manchester M5 4WT, United Kingdom.
authors.forename: Roger H
authors.initials: RH
authors.lastname: Bisby
authors.affiliation: Research Complex at Harwell, Central Laser Facility, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0FA, United Kingdom.
authors.forename: Stanley W
authors.initials: SW
authors.lastname: Botchway
authors.affiliation: University of Salford, Biomedical Research Centre, Salford, Greater Manchester M5 4WT, United Kingdom.
authors.forename: John A
authors.initials: JA
authors.lastname: Hadfield
authors.affiliation: Research Complex at Harwell, Central Laser Facility, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0FA, United Kingdom.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Parker
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D001632:Bibenzyls / Q000737:chemistry*; D016466:CHO Cells; D016923:Cell Death; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004354:Drug Screening Assays, Antitumor; D006834:Hydrazines / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D018613:Microscopy, Confocal; D010539:Permeability; D017785:Photons; D017319:Photosensitizing Agents / Q000737:chemistry; D010789:Phototherapy / Q000379:methods*; D011419:Propidium / Q000737:chemistry; D020033:Protein Isoforms; D019265:Spectroscopy, Near-Infrared
chemical_list: C417561:Alexa 488 hydrazide; D017304:Annexin A5; D000970:Antineoplastic Agents; D001632:Bibenzyls; D006834:Hydrazines; D017319:Photosensitizing Agents; D020033:Protein Isoforms; D011419:Propidium; C040105:combretastatin