aluminum-tetrasulfophthalocyanine and aluminum-phthalocyanine

Topics: Antineoplastic Agents; Follow-Up Studies; Hematoporphyrin Derivative; Humans; Indoles; Lasers; Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Spectrometry, Fluorescence; Time Factors

Photodynamic therapy of cancer is a promising treatment based on the tumor-specific accumulation of photosensitizers followed by irradiation with visible light which induces tumor cell death. The effect of different preincubation times on the photosensitization efficiency of the phthalocyanines AlPc and AlPcS4 was investigated in lymphoblastoid CCRF-CEM cells under conditions that allow maximal uptake of the sensitizers. First, the time course for the uptake of AlPcS4 and AlPc by CCRF-CEM cells and by the pheochromocytoma PC12 cells was compared. The uptake of AlPcS4 by CCRF-CEM cells was not significantly different after 6 h or 24 h incubation, but the photosensitization efficiency of the phthalocyanine was much higher when a 24 h preincubation period was used, with a fluence rate of 5 mW/cm2. However, for a fluence rate of 10 mW/cm2, the photosensitization efficiency of AlPcS4 was almost completely independent of the preincubation time (6 h vs. 24 h) with the phthalocyanine. When the cells were preincubated with 1 micromol/L AlPc for 10 min or 6 h, which allows the same accumulation of sensitizer by the cells, no significant effect of the incubation time on the photodynamic inactivation of CCRF-CEM cells was observed, with fluence rates of 5 mW/cm2 or 10 mW/cm2, for different light doses. Confocal fluorescence microscopy studies did not reveal differences in the localization of the phthalocyanines after maximal uptake was reached. The results show that the preincubation time with AlPcS4, after the maximal uptake is reached, affects cell growth to an extent depending on the fluence rate used, and this effect was not due to a major redistribution of the sensitizer during incubation. However, this was not observed when AlPc was used.

Topics: Adrenal Gland Neoplasms; Aluminum; Animals; Cell Division; Humans; Indoles; Kinetics; Light; Lymphocytes; Organometallic Compounds; PC12 Cells; Pheochromocytoma; Photosensitizing Agents; Rats; Time Factors; Tumor Cells, Cultured

One of the most frequent complications of extracapsular cataract surgery is posterior capsule opacification (PCO), which is caused by proliferation and migration of retained lens epithelial cells on the posterior capsule surface. This complication leads to a reduction in visual acuity. Depending on the age of the patients, the incidence varies between 15 and 50%. Selective elimination of these cells would therefore prevent PCO. Phthalocyanines (Pc) are efficient photosensitizers of various carcinoma cell lines. Their attractive property is the strong absorption of visible light above 600 nm. Upon absorption of a photon, the sensitizer in its excited state can be either directly cytotoxic or produce reactive oxygen species type I (free radicals) or type II (singlet oxygen), which become the mediator of cellular injury by affecting membranes and subcellular organelles. Preconfluent cultures of porcine lens epithelial cells were incubated with aluminum phthalocyanine (AlPc) or aluminum phthalocyanine transulfonate (AlPcS4) in concentrations ranging from 0-20 microM for 1 h at 37 degrees C. Thereafter, cultures were exposed to red light for 5 min. A 300 W quartz halogen light bulb equipped with a cut-off filter that allowed transmission of the whole spectrum above 600 nm was used for activation of the sensitizers. To evaluate the effect of fluoride, 5 mM NaF was added to the dye-loaded cells immediately before light exposure. This treatment had no toxic effect. Subsequently, the treated cells were incubated in culture medium for 24 h. After trypsinization, the cell number was determined by a cell counter. Prior to light exposure neither AlPc nor AlPcS4 was toxic in corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cell Count; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Epithelium; Indoles; Lens Capsule, Crystalline; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents; Swine

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

A comparison of time-dependent localization patterns between lower, asymmetrical (AIPCS2a) and higher, symmetrical (AIPCS4) sulfonates of aluminum phthalocyanines in human malignant melanoma LOX transplanted to athymic nude mice from 1 to 120 hr after i.v. administration was made by means of laser scanning fluorescence microscopy. The lipophilic AIPCS2a was distributed mainly in tumor cells, while the hydrophilic AIPCS4 localized only in the vascular stroma of the tumor tissue. Concomitantly, comparative observations on the killing mechanism of photodynamic effects after treatment with a much lower i.v. dose of AIPCS2a and AIPCS4 plus laser light on the human tumor LOX were also made by morphological studies. Light and electron microscopy showed that there was a direct, extensive, photo-damaging action on all organelles and nuclear structure in the tumor cells after PDT with AIPCS2a; whereas the photo-induced injury to the tumor tissue after treatment with AIPCS4 and light was largely the consequence of initial functional vasogenic response and ultimate damage to vascular structure. These findings correlate well with the different localization patterns of the 2 dyes observed in human tumor tissues.

Topics: Animals; Female; Indoles; Melanoma; Mice; Mice, Inbred BALB C; Microscopy, Electron; Microscopy, Fluorescence; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents; Sulfonic Acids; Time Factors; Transplantation, Heterologous