title: One- and two-photon activated phototoxicity of conjugated porphyrin dimers with high two-photon absorption cross sections.
abstract: Two-photon excited photodynamic therapy (PDT) has the potential to provide a highly targeted treatment for neoplastic diseases, as excitation can be pin-pointed to small volumes at the laser focus. In addition, two-photon PDT offers deeper penetration into mammalian tissue due to the longer wavelength of irradiation. Here we report the one-photon and two-photon excited PDT results for a collection of conjugated porphyrin dimers with high two-photon absorption cross sections. These dimers demonstrate high one-photon PDT efficacy against a human ovarian adenocarcinoma cell line (SK-OV-3) and exhibit no significant dark-toxicity at concentrations of up to 20 microM. Their one-photon excited PDT efficiencies, following irradiation at 657 nm, approach that of Visudyne, a drug used clinically for PDT. We investigated and optimised the effect of the photosensitizer concentration, incubation time and the light dose on the PDT efficacy of these dimers. These studies led to the selection of P2C2-NMeI as the most effective porphyrin dimer. We have demonstrated that P2C2-NMeI undergoes a two-photon activated process following excitation at 920 nm (3.6-6.8 mW, 300 fs, 90 MHz) and compared it to Visudyne. We conclude that the in vitro two-photon PDT efficacy of P2C2-NMeI is about twice that of Visudyne. This result highlights the potential of this series of porphyrin dimers for two-photon PDT.
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX13TA, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Dahlstedt
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Collins
authors.forename: Milan
authors.initials: M
authors.lastname: Balaz
authors.forename: Marina K
authors.initials: MK
authors.lastname: Kuimova
authors.forename: Mamta
authors.initials: M
authors.lastname: Khurana
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: David
authors.initials: D
authors.lastname: Phillips
authors.forename: Harry L
authors.initials: HL
authors.lastname: Anderson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019281:Dimerization; D005260:Female; D006801:Humans; D007259:Infrared Rays; D010051:Ovarian Neoplasms / Q000628:therapy; D010778:Photochemotherapy / Q000379:methods*; D017785:Photons; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D012995:Solubility; D000077362:Verteporfin
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin