Presence Of Photofrin Research Articles

Energy Transfer between AGuIX Nanoparticles and Photofrin under Light or X-ray Excitation for PDT Applications.

Photodynamic therapy is an accepted therapy cancer treatment. Its advantages encourage researchers to delve deeper. The use of nanoparticles in PDT has several advantages including the passive targeting of cancer cells. The aim of this article is to evaluate the effectiveness of AGuIX nanoparticles (activation and guiding of irradiation by X-ray) in the presence or absence of a photosensitizer, Photofrin, under illumination of 630 nm or under X-ray irradiation. The goal is to improve local tumor control by combining PDT with low-dose-X-ray-activated NPs in the treatment of locally advanced metastatic lung cancer. The study of the energy transfer, which occurs after excitation of Gd/Tb chelated in AGuIX in the presence of Photofrin, was carried out. We could observe the formation of singlet oxygen after the light or X-ray excitation of Gd and Tb that was not observed for AGuIX or Photofrin alone, proving that it is possible to realize energy transfer between both compounds.

Electric field-assisted delivery of photofrin to human breast carcinoma cells.

The influence of electroporation on the Photofrin uptake and distribution was evaluated in the breast adenocarcinoma cells (MCF-7) and normal Chinese hamster ovary cells (CHO) lacking voltage-dependent channels in vitro. Photofrin was used at a concentration of 5 and 25 μM. The uptake of Photofrin was assessed using flow cytometry and fluorescence microscopy methods. Cells viability was evaluated with crystal violet assay. Our results indicated that electropermeabilization of cells, in the presence of Photofrin, increased the uptake of the photosensitizer. Even at the lowest electric field intensity (700 V/cm) Photofrin transport was enhanced. Flow cytometry results for MCF-7 cells revealed ~1.7 times stronger fluorescence emission intensity for cells exposed to Photofrin and electric field of 700 V/cm than cells treated with Photofrin alone. Photofrin was effective only when irradiated with blue light. Our studies on combination of photodynamic reaction with electroporation suggested improved effectiveness of the treatment and showed intracellular distribution of Photofrin. This approach may be attractive for cancer treatment as enhanced cellular uptake of Photofrin in MCF-7 cells can help to reduce effective dose of the photosensitizer and exposure time in this type of cancer, diminishing side effects of the therapy.

The influence of oxygen on the radiosensitizing activity of Photofrin II and hypericin

Several clinical studies, as well as investigations performed on tissue cultures and murine tumor models, have demonstrated the in vitro and in vivo efficacy of Photofrin II and hypericin as radiosensitizing agents. The mechanisms involved in the radiosensitizing action of Photofrin II and hypericin are partially understood; the recognition of the major role performed by oxygen regarding the modulation of cellular radiosensitivity has prompted the present investigations on the relevance of oxygenation for the success of Photofrin II or hypericin-based radiation therapy of tumors. RT4 human bladder carcinoma cell lines were seeded and incubated with various concentrations of Photofrin II or hypericin under ambient and 5% oxygen levels. The cells were irradiated with ionizing radiation between 1 and 6 Gy. The same experiments were repeated with Photofrin II and hypericin alone, without radiation. The cell survival was evaluated. The results demonstrated an increase of radiation-induced cell damage in the presence of Photofrin II and hypericin, respectively, when sufficient oxygen was available. Low levels of oxygen reduced the activity of Photofrin II as well as of hypericin as a radiosensitizer, with minimal tumor damage ( p < 0.05 in a Student t-test). The mechanism of action of Photofrin II and hypericin as radiosensitizers requires the presence of sufficiently high oxygen concentrations.

Effect of Photofrin II as a radio-sensitizing agent in two different oesophageal carcinoma cell lines

Background and Purpose: In spite of major advances in cancer treatment, the prognosis of patients with oesophageal carcinoma remains poor. Squamous cell carcinoma and adenocarcinoma account for 95% of all oesophageal tumors, although other histological subtypes are occasionally seen. We aimed to evaluate whether Photofrin II can enhance the effect of ionizing radiation on oesophageal cancer in an in vitro tumor model. Material and Methods: A human oesophageal squamous cancer cell line (OE-21) and a human oesophageal adenocarcinoma cell line (OE-33) were evaluated with and without incubation with Photofrin II. Cells were irradiated using doses ranging from 0 to 8 Gy. The response rate of the cells to irradiation was evaluated by a tetrazolium-based colorimetric assay, similar to the MTT test, with the aim to determine the efficiency of Photofrin II as a radiation sensitizer in comparison to irradiation alone. Results: The OE-21 cell line demonstrated a significantly reduced cellular survival rate, when irradiated in the presence of Photofrin, as compared to a control group irradiated in the absence of Photofrin II. For the OE-33 cell line, no significant differences were found between the group treated with Photofrin II and the control group. Conclusion: Our results demonstrate in an in vitro model that Photofrin II may act as a radio-sensitizer in squamous cell oesophageal cancer, but not in oesophageal adenocarcinoma.

Effects of Photofrin® Photodynamic Action on Mitochondrial Respiration and Superoxide Radical Generation

Cyanide-resistant respiration increases after irradiation of isolated mitochondria in the presence of Photofrin. This suggests an enhancement of electron leakage which has been evaluated by measuring superoxide radical formation in submitochondrial particles incubated with 6 micrograms/ml Photofrin in the medium and irradiated with increasing doses of light at 365 nm. After a dose of 4.5 kJ/m2 has been delivered, superoxide generation increases by a factor of approximately 2.5 at the level of NADH dehydrogenase and by a factor approximately 1.5 in the cyt bc1 region. These effects have been compared with changes observed in NADH-, succinate- and ascorbate-driven respiration and their implications discussed.