A novel ~(10)B-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

摘要

The synthesis of a Zn(II)-phthalocyanine derivative bearing four ~(10)B-enriched o-carboranyl units (~(10)B-ZnB_4Pc) and its natural isotopic abundance analogue (ZnB_4Pc) in the peripheral positions of the tetraazaisoindole macrocycle is presented.The photophysical properties of ZnB_4Pc,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,ZnB_4Pc,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 ZnB_4Pc were still present in the serum.Analogously,irradiation of the ~(10)B-ZnB_4Pc-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.