title: A novel 10B-enriched carboranyl-containing phthalocyanine as a radio- and photo-sensitising agent for boron neutron capture therapy and photodynamic therapy of tumours: in vitro and in vivo studies.
abstract: The synthesis of a Zn(ii)-phthalocyanine derivative bearing four 10B-enriched o-carboranyl units (10B-ZnB4Pc) and its natural isotopic abundance analogue (ZnB4Pc) in the peripheral positions of the tetraazaisoindole macrocycle is presented. The photophysical properties of ZnB4Pc, as tested against model biological systems, were found to be similar with those typical of other photodynamically active porphyrin-type photosensitisers, including a singlet oxygen quantum yield of 0.67. The carboranyl-carrying phthalocyanine was efficiently accumulated by B16F1 melanotic melanoma cells in vitro, appeared to be partitioned in at least some subcellular organelles and, upon red light irradiation, induced extensive cell mortality. Moreover, ZnB4Pc, once i.v.-injected to C57BL/6 mice bearing a subcutaneously transplanted pigmented melanoma, photosensitised an important tumour response, provided that the irradiation at 600-700 nm was performed 3 h after the phthalocyanine administration, when appreciable concentrations of ZnB4Pc were still present in the serum. Analogously, irradiation of the 10B-ZnB4Pc-loaded pigmented melanoma with thermal neutrons 24 h after injection led to a 4 day delay in tumour growth as compared with control untreated mice. These results open the possibility to use one chemical compound as both a photosensitising and a radiosensitising agent for the treatment of tumours by the combined application of photodynamic therapy and boron neutron capture therapy.
authors.affiliation: Department of Biology, University of Padova, Via Ugo Bassi 58B, 35121, Padova, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Friso
authors.forename: Gabrio
authors.initials: G
authors.lastname: Roncucci
authors.forename: Donata
authors.initials: D
authors.lastname: Dei
authors.forename: Marina
authors.initials: M
authors.lastname: Soncin
authors.forename: Clara
authors.initials: C
authors.lastname: Fabris
authors.forename: Giacomo
authors.initials: G
authors.lastname: Chiti
authors.forename: Paolo
authors.initials: P
authors.lastname: Colautti
authors.forename: Juan
authors.initials: J
authors.lastname: Esposito
authors.forename: Laura
authors.initials: L
authors.lastname: De Nardo
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardo Rossi
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Francesca
authors.initials: F
authors.lastname: Giuntini
authors.forename: Lara
authors.initials: L
authors.lastname: Borsetto
authors.forename: Giulio
authors.initials: G
authors.lastname: Jori
mesh_terms: D000818:Animals; D001895:Boron / Q000737:chemistry; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000528:radiation effects; D054833:Isoindoles; D007554:Isotopes; D008081:Liposomes; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000528:radiation effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000528:radiation effects; D012878:Skin Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D007211:Indoles; D054833:Isoindoles; D007554:Isotopes; D008081:Liposomes; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D001895:Boron; C013647:phthalocyanine