title: Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity.
abstract: Photodynamic therapy (PDT) is an emerging cancer treatment modality based on the excitation of a nontoxic photosensitizer with harmless visible light to produce reactive-oxygen species (ROS) that induce apoptosis and/or necrosis in cancer cells. As the efficacy of this therapy strongly depends of the nature of the photosensitizer, there is a great interest to develop new photoactive molecules. Here we report for the first time the synthesis, characterization and bioactivity of metal complexes between the non-aromatic expanded porphyrin, namely 20-[[4'-(Trimethylsilyl)ethoxycarbonyl]phenyl-2,13-dimethyl-3,12-diethyl-[24] iso-pentaphyrin (PCRed) and Zn(II) [Zn(II)-PCRed] or Lu(III) [Lu(III)-PCRed]. The complexation of these two diamagnetic heavy metal ions to PCRed improved the properties of the free photosensitizer as a PDT drug. We discovered that the 1:1 complex between PCRed and Lu(III) significantly increases the cellular uptake, ROS production and antiproliferative capacity in four cancer cell lines. Our study shows that metal complexation is a useful strategy to potentiate iso-pentaphyrin as a PDT drug.
authors.affiliation: Department of Chemical Science, University of Udine, Via del Cotonificio, 108, 33100 Udine, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ballico
authors.forename: Valentina
authors.initials: V
authors.lastname: Rapozzi
authors.forename: Luigi E
authors.initials: LE
authors.lastname: Xodo
authors.forename: Clara
authors.initials: C
authors.lastname: Comuzzi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008187:Lutetium / Q000737:chemistry*; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D008187:Lutetium; D015032:Zinc