aluminum-phthalocyanine-disulfonate and Melanoma

Topics: Cell Line, Tumor; Humans; Indoles; Liposomes; Melanoma; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Spheroids, Cellular

Photodynamic therapy is a modality of treatment for tumors. The photochemical interactions of sensitizer, light and molecular oxygen produce reactive oxygen species (ROS) such as singlet oxygen, peroxide, hydroxyl radical and superoxide ion. The tumor is destroyed either by the formation of highly reactive singlet oxygen (type II mechanism) or by the formation of radical products (type 1 mechanism) generated in an energy transfer reaction. The resulting damage to organelles within malignant cells leads to tumor ablation. The cellular effects include membrane damage, mitochondrial damage and DNA damage. A new treatment modality called sonodynamic therapy has been developed, in which the ultrasound-induced cytotoxicity of sonochemical sensitizers inhibits tumor growth. In this study, the promising new generation of sensitizers - phthalocyanines - were used to induce the photodamage. In addition, we applied an ultrasound treatment to support the photodynamic effect. We report on the production of ROS in G361 melanoma cells. Light-emitting diodes were used to evoke the photodynamic effect. Changes in cells were evaluated using fluorescence microscope and atomic force microscopy. The quantitative ROS production changes in relation to sensitizer concentration, irradiation doses and ultrasound intensity were proved by a fluororeader. Our results showed the highest generation of ROS within G361 melanoma cells was achieved at an irradiation dose of 15 Jcm(-2) followed by ultrasound treatment at intensity of 2 Wcm(-2) and frequency of 1 MHz in the presence of 100 muM chloroaluminum phthalocyanine disulfonate (ClAlPcS2). These results suggest that ClAlPcS2 is a potential photosensitizer and sonosensitizer for sonodynamic or photodynamic treatment of cancer.

Topics: Cell Line, Tumor; Combined Modality Therapy; Dose-Response Relationship, Drug; Fluorometry; Humans; Indoles; Melanoma; Microscopy, Atomic Force; Microscopy, Fluorescence; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Skin Neoplasms; Treatment Outcome; Ultrasonic Therapy

Photodynamic therapy (PDT) is a new treatment modality of tumours. The photochemical interactions of sensitizer, light, and molecular oxygen produce singlet oxygen and other forms of active oxygen, such as peroxide, hydroxyl radical and superoxid anion. Phthalocyanine ClAlPcS(2), belonging among the promising second generation of sensitizers, was tested as an inducer of photodamage. We report the production of reactive oxygen species (ROS) and the phototoxicity of ClAlPcS(2) assessed using G361 melanoma cells. A semiconductor laser (lambda=675nm, output power 21mW) was used as a source for evocation of the photodynamic effect. ROS generation and H(2)O(2) release after PDT on G361 cells were detected using probe CM-H(2)DCFDA and recorded by luminescence spectrometer. Viability studies show, that the optimum phototoxic effect tested on G361 melanoma cells was determined in the combination of laser dose of 25Jcm(-2) and phthalocyanine ClAlPcS(2) concentration of 5microg/ml. This combination of phthalocyanine concentration and corresponding radiation dose was lethal for melanoma cells.

Topics: Cell Line, Tumor; Humans; Indoles; Lipoproteins, LDL; Melanoma; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species

By means of laser scanning fluorescence microscopy the intratumoral localization patterns of several photosensitizers in LOX tumors in nude mice were studied. Lipophilic dyes such as TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), AlPCS1 (aluminium phthalocyanine monosulfonate) and AlPCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h postinjection and the fluorescence was still observable 120 h postinjection. The more hydrophilic dyes such as TPPS3 (tetraphenylporphine trisulfonates), TPPS4 (tetraphenylporphine tetrasulfonates), and AlPCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h postinjection. 120 h postinjection no significant fluorescence of these dyes could be seen in the tumors. P-II (Photofrin II), 3-THPP [tetra(3-hydroxyphenyl)porphine], TPPS2o (tetraphenylporphine disulfonates with the sulfonate groups on opposite rings) and AlPCS3 (aluminum phthalocyanine trisulfonates) had a combined localization pattern, i.e. a strongly cytoplasmic membrane-localizing pattern and a weakly intracellular distribution pattern, although some fluorescence could be seen in the tumorous stroma. The data are discussed in relation to what is known about the in vivo photosensitizing efficiency of some of the dyes.

Topics: Animals; Cell Line; Dihematoporphyrin Ether; Female; Fluorescent Dyes; Hematoporphyrins; Humans; Indoles; Lasers; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Phase-Contrast; Organometallic Compounds; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents

Athymic nude mice with human tumors transplanted to one of the hind legs were given aluminium phthalocyanine disulfonate (AlPcS2) intraperitoneally. Twenty-four hours after the injection the mice were placed with the tumor in the sample position in a fluorescence spectrometer with modulated excitation. Exposure of the tumors to laser light at a fluence rate of 50-200 mW/cm2 led to a rapid transient reduction by up to 50% of the phthalocyanine fluorescence of the tumor. After the laser irradiation the fluence rate of the fluorescence increased almost up to the initial value within a few minutes. This finding should be taken into account when optimal fluence rates and dose fractionation schemes are sought for photodynamic therapy.

Topics: Animals; Cell Line; Female; Humans; Indoles; Isoindoles; Melanoma; Mice; Mice, Nude; Neoplasm Transplantation; Organometallic Compounds; Photochemotherapy; Pigments, Biological; Radiation-Sensitizing Agents; Spectrometry, Fluorescence; Transplantation, Heterologous