pheophorbide-a and Disease-Models--Animal

Our previous study has shown a prolonged retention and accumulation of Zn-pheophorbide a, a water-soluble derivative of chlorophyll a, in tumor tissue (Szczygiel et al. [19]). This prompted us to further evaluate the phototherapeutic potential of this photosensitizer of excellent physicochemical properties.. Cellular uptake of Zn-pheophorbide, its localization in cells, cytotoxicity, phototoxicity and cell death mechanisms were studied in human adenocarcinoma cell lines: A549, MCF-7 and LoVo. The PDT efficacy was tested against A549 tumors growing in nude mice.. Zn-pheophorbide a even at very low concentrations (∼1×10(-6)M) and at low light doses (5J/cm(2)) causes a strong photodynamic effect, leading to 100% cell mortality. Confocal microscopy showed that in contrast to most derivatives of chlorophyll, Zn-pheophorbide a does not localize to mitochondria. The photodynamic effects and the cell death mechanisms of Zn-pheophorbide a, its Mg analog (chlorophyllide a) and Photofrin were compared on the A549 cells. Zn-pheophorbide a showed the strongest photodynamic effect, at low dose killing all A549 cells via apoptosis and necrosis. The very high anti-cancer potential of Zn-pheophorbide was confirmed in a photodynamic treatment of the A549 tumors. They either regressed or were markedly inhibited for up to 4 months after the treatment, resulting, on average, in a 5-fold decrease in tumor volume.. These results show that Zn-pheophorbide a is a very promising low-cost, synthetically easily accessible, second generation photosensitizer against human cancer.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Chlorophyll; Disease Models, Animal; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Photochemotherapy; Photosensitizing Agents; Treatment Outcome; Zinc

In this study, we examined the therapeutic effect of photodynamic therapy (PDT) using the photosensitizer Na-Pheophorbide a (Na-Phde a) on osteomyelitis models in rats.. Osteomyelitis is one of the most serious infectious problems in the orthopedic field. Recently, as a new clinical approach against septic arthritis, an experimental in vivo and in vitro model for the inactivation of methicillin-resistant-Staphylococcus aureus by PDT using Na-Phde a has been developed.. Methicillin-sensitive Staphylococcus aureus (MSSA) was injected into the tibia of the rats to create osteomyelitis models (n = 10, 10 legs). A total of 560 μmol/l of Na-Phde a solution was injected into five of these tibial osteomyelitis models (five legs) 48 h after the initial MSSA infection. Sixty minutes after the Na-Phde a injection, a semiconductor laser (125 mW, 670 nm) was used to irradiate the models for 10 min with a total energy of 93.8 J/mm(2). As a control group, five rats (five legs) were treated with a phosphate buffered saline injection at 48 h after MSSA infection. Weight and leg perimeter changes were plotted. Bacterial growth, histological examination and radiological examination were evaluated at 14 days after initial treatment.. PDT with Na-Phde a significantly prevented leg swelling. In the PDT group, bone destruction owing to osteomyelitis was inhibited not only histologically but also radiographically.. The results in these experiments show that PDT using Na-Phde a improved osteomyelitis in rats. This suggests that PDT using Na- Phde a can be a useful treatment for osteomyelitis.

Topics: Animals; Biopsy, Needle; Chlorophyll; Disease Models, Animal; Female; Immunohistochemistry; Osteomyelitis; Photochemotherapy; Photosensitizing Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Staphylococcal Infections; Statistics, Nonparametric; Tibia; Treatment Outcome