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1.
Org Biomol Chem ; 6(20): 3732-40, 2008 Oct 21.
Article in English | MEDLINE | ID: mdl-18843403

ABSTRACT

We describe the total synthesis and biological properties of a new carboranyl-containing chlorin (TPFC) that might find application as a dual sensitizer in the PDT and BNCT treatment of cancer. TPFC was found to be non-toxic in the dark but showed extensive photosensitizing ability both in vitro and in vivo despite its relatively low singlet oxygen quantum yield. In particular, TPFC exhibited significant photosensitizing activity against highly pigmented melanotic melanoma tumors in mice.


Subject(s)
Boron Compounds/chemical synthesis , Boron Compounds/pharmacology , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/pharmacology , Porphyrins/chemical synthesis , Porphyrins/pharmacology , Animals , Boron Compounds/metabolism , Boron Compounds/toxicity , Boron Neutron Capture Therapy , Cell Line, Tumor , Cell Survival/drug effects , Humans , Intracellular Space/metabolism , Mice , Photochemistry , Photochemotherapy , Photosensitizing Agents/metabolism , Photosensitizing Agents/toxicity , Porphyrins/chemistry , Porphyrins/metabolism , Porphyrins/toxicity
2.
J Photochem Photobiol B ; 89(2-3): 131-8, 2007 Dec 14.
Article in English | MEDLINE | ID: mdl-17977739

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.


Subject(s)
Boron Neutron Capture Therapy/methods , Melanoma, Experimental/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/metabolism , Porphyrins/metabolism , Animals , Cell Line, Tumor , Darkness , Female , Mice , Mice, Inbred C57BL , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/pharmacokinetics , Porphyrins/administration & dosage , Porphyrins/pharmacokinetics , Skin Neoplasms/drug therapy
3.
Photochem Photobiol Sci ; 5(1): 39-50, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16395426

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.


Subject(s)
Boron Neutron Capture Therapy/methods , Indoles/administration & dosage , Melanoma, Experimental , Organometallic Compounds/administration & dosage , Photochemotherapy , Skin Neoplasms , Animals , Boron/chemistry , Cell Death/drug effects , Cell Death/radiation effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Combined Modality Therapy , Disease Models, Animal , Female , In Vitro Techniques , Indoles/chemical synthesis , Indoles/radiation effects , Isoindoles , Isotopes , Liposomes , Melanoma, Experimental/drug therapy , Melanoma, Experimental/radiotherapy , Mice , Mice, Inbred C57BL , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/radiation effects , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/radiation effects , Skin Neoplasms/drug therapy , Skin Neoplasms/radiotherapy , Structure-Activity Relationship , Time Factors
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