title: Tumour-localizing and -photosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP).
abstract: A water-soluble meso-substituted porphyrin (H(2)TCP) bearing 36 boron atoms, which appeared to be an efficient photodynamic sensitiser (singlet oxygen quantum yield=0.44), was studied for its accumulation by murine melanotic melanoma cells (B16F1). The amount of H(2)TCP in the cells increased with the porphyrin dose in the incubation medium up to, and at least, 100 microM concentrations with no significant cytotoxic effect in the dark. Moreover, the H(2)TCP uptake increased with the incubation time reaching a plateau value corresponding with the recovery of 0.4 nmol of H(2)TCP per mg of cell proteins after 24h incubation. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly, exhibiting a discrete distribution in the cytoplasm with a pattern which was closely similar to that observed for the endosomal probe Lucifer yellow. The photosensitising efficiency of the H(2)TCP toward B16F1 cells was studied for different irradiation (1-15 min) and incubation (1-24 h) times. Nearly complete (>95%) cell mortality was obtained upon incubation with 20 microM H(2)TCP and 10 min irradiation with red light (600-700 nm, 20 mW/cm(2)). The porphyrin was also accumulated in appreciable amounts by the tumour tissue after intravenous injection to C57BL/6 mice bearing a subcutaneously transplanted melanotic melanoma. Maximum accumulation in the tumour was achieved by administration of H(2)TCP dissolved in the ternary mixture 20% dimethylsulfoxide (DMSO)-30% polyethyleneglycol (PEG 400)-50% water. Thus, this porphyrin could act as both a photodynamic therapy agent and a radiosensitising agent for boron neutron capture therapy.
authors.affiliation: Department of Biology, University of Padova, via Ugo Bassi, 58/B, 35121 Padova, Italy. clara.fabris@unipd.it
authors.forename: Clara
authors.initials: C
authors.lastname: Fabris
authors.forename: M Graça H
authors.initials: MG
authors.lastname: Vicente
authors.forename: Erhong
authors.initials: E
authors.lastname: Hao
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Friso
authors.forename: Lara
authors.initials: L
authors.lastname: Borsetto
authors.forename: Giulio
authors.initials: G
authors.lastname: Jori
authors.forename: Giovanni
authors.initials: G
authors.lastname: Miotto
authors.forename: Paolo
authors.initials: P
authors.lastname: Colautti
authors.forename: Davide
authors.initials: D
authors.lastname: Moro
authors.forename: Juan
authors.initials: J
authors.lastname: Esposito
authors.forename: Alice
authors.initials: A
authors.lastname: Ferretti
authors.forename: Carlo Riccardo
authors.initials: CR
authors.lastname: Rossi
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Guido
authors.initials: G
authors.lastname: Sotti
authors.forename: Marina
authors.initials: M
authors.lastname: Soncin
mesh_terms: D000818:Animals; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D003624:Darkness; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D012878:Skin Neoplasms / Q000188:drug therapy
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C527224:meso-tetra(4-nido-carboranylphenyl)porphyrin