• Title/Summary/Keyword: PDT photosensitizer

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Photodynamic Therapy induced Cell Death using ALA and 632nm Diode Laser in A549 Lung Cancer Cells (A549 폐암세포주에서 ALA와 632nm Diode Laser를 이용한 광역학치료 유도성 세포사)

  • Kim, Youn Seup;Park, Jae Seuk;Jee, Young Koo;Lee, Kye Young
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.2
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    • pp.178-186
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    • 2004
  • Background : Photodynamic therapy (PDT) is a new therapeutic method aimed at the selective destruction of cancer cells. The outcome is death of cancer cells through apoptosis or necrosis. The aim of this study was to investigate the characterization of PDT induced cell death in A549 lung cancer cells. Materials and methods : A549 cells were used as the lung cancer cell. 5 aminolevulinic acid (ALA) was used as the photosensitizer and a 632nm diode laser (Biolitec, Germany) as the light source. Cells were incubated with various concentrations of ALA. The 632nm diode laser was then administered for various laser irradiation times. The treated cells were incubated with 24, 48 and 72 hours. The cell viabilities were measured using the crystal violet assay and light microscopy. To observe the cell death mechanism after PDT, cells were observed under fluorescence microscopy after double staining with Hoechst 33342 and propium iodide after PDT. Results : In the crystal violet assay at 24 hours after PDT with a $3.2J/cm^2$ laser irradiation power, the cell viabilities were $89.56{\pm}4.11$, $87.67{\pm}5.48$, and $69.37{\pm}8.84$ with ALA concentrations of 10, 100, and $1mg/m{\ell}$, respectively. In crystal violet assay at 24 hours after PDT with $1mg/m{\ell}$ of ALA, the cell viabilities were $74{\pm}19.85$, $55{\pm}6.1$, and $49.06{\pm}16.64%$ with 1.6, 3.2 and $6.4J/cm^2$ laser irradiation powers, respectively. However, increasing the interval time after PDT did not change the cell viabilities. In the apoptosis assay, photodynamic therapy was inducing the apoptotic cell death. Conclusions : This study shows the apoptotic anticancer effect of photodynamic therapy in A549 lung cancer cells. However, further evaluations with other cancer cells and photosensitizers are necessary.

The Synthetic Approaches to Modify Methyl (Pyro)pheophorbide a

  • Wang, Jin-Jun;Han, Guang-Fan;Lee, Jong-Cheol;Shim, Young-Key
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.178-181
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    • 2002
  • Pyropheophorbide and pheophorbide-photosensitizers as chlorin analogues are promising new compounds for PDT because the chlorin analogues are activated with much longer red light at > 670nm and produce less long-term normal tissue phototoxicity than Photofrin. The various chlorin derivatives can be obtained by moditying peripheral substituted group among which meso-H, vinyl group and exocyclic ring are the most active positions. These characteristics prompted us to introduce various groups for constructing modified pyropheophorbide and pheophorbide a compounds. A stereospecific introduction of various double bonds at 3-position was performed to methylpheophorbide a to give a long hydrophobic moiety and cyclic derivatives. Chlorin-C$_{60}$ dyad and chlorin- $C_{60}$-porphyrin triad also were easily prepared by the reaction of terminal aldehyde of methyl pyropheophorbide a. For the reaction on meso $\delta$-position bromination and Vismeier formylation can occur. N,N-dimethylaminoacrolein also reacted on $\delta$-position and was cyclized to isobacteriochlorin, but other modification has not been succeeded. Exocyclic keto function was also modified to give purpurin derivatives, bicyclic and spiro compounds. In this presentation we report a series of modified pyropheophorbide and pheophorbide a derivatives.s.

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Efficiency Factors of Singlet Oxygen Generation from Core-Modified Expanded Porphyric : Tetrathiarubyrin in Ethanol

  • Ha, Jeong Hyeon;Jeong, Guk Yeong;Kim, Min Seon;Lee, Yang Hun;Sin, Gu;Kim, Yong Rok
    • Bulletin of the Korean Chemical Society
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    • v.22 no.1
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    • pp.63-67
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    • 2001
  • The photophysical properties and the singlet oxygen generation efficiency of tetrathiarubyrin have been investigated to elucidate the possibility of its use as a photodynamic therapy (PDT) photosensitizer by steady-state and time-resolved spectroscopic methods. The observed photophysical properties were affected by various molecular aspects, such as extended ${\pi}conjugation$, structural distortion, and internal heavy atom. The steady-state electronic absorption spectrum was red-shifted due to the extended $\pi-conjugation$, and the spin orbital coupling was enhanced by the structural distortion and the internal heavy atom effect. As a result of the enhanced spin orbital coupling, the triplet quantum yield increased to 0.90 $\pm$ 0.10 and the triplet state lifetime was shortened to 7.0 $\pm$ 1.2 ${\mu}s$. Since the triplet state decays at a relatively faster rate, the efficiency of the oxygen quenching of the triplet state decreases. The singlet oxygen quantum yield was estimated to be 0.52 $\pm$ 0.02, which is somewhat lower than expected. On the other hand, the efficiency of singlet oxygen generation during the oxygen quenching of triplet state, $f{\Delta}^T$, is near unity. Such high efficiency of singlet oxygen generation can be explained by the following two possible factors: The hydrogen bonding of ethanol which impedes the deactivation pathway of the charge transfer complex with oxygen to the ground state, the less probability of the aggregation formation.

Photodynamic effect of Photofrin and Radachlorin against Staphylococcus aureus and Staphylococcus epidermidis (황색포도알균과 표피포도알균에 대한 포토프린과 라다클로린의 광역학 효과)

  • Seo, Choong-Won;Ryu, Jae-Gi;Kwon, Pil-Seung
    • Journal of Digital Convergence
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    • v.12 no.6
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    • pp.407-414
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    • 2014
  • The aim of this study was to evaluate the photodynamic therapy effects against staphylococci using Photofrin and Radachlorin with Light emitting diode(LED). Experimental methods, The bacterial suspensions containing Staphylococcus aureus and Staphylococcus epidermidis at $1{\times}10^5$ were prepared and diluted to different concentrations of photosensitizer, Photofrin or Radachlorin, on 1.25, 2. 5,5 and $10{\mu}g/ml$. The bacterial suspensions were exposed to 630 and 670 nm LED light at the energy density of 14.4 and $19.8J/cm^2$, respectively. The CFU results of S. aureus and S. epidermidis were showed 33 and 50 colony forming at $5{\mu}g/ml$ of Photofrin, respectively and both of them perfectely were dead at $5{\mu}g/ml$ of Radachlorin. The fluorescent intensity by flow cytometry was showed the increase in the dead cells than the normal cells. In the TEM photograph, the damage of bacterial membrane and the distortion of cell morphology were observed. These results suggest that photodynamic therapy combine with Photofrin and Radachlorin can be applied a new modality for antibacterial therapy.

in vitro and in vivo Photodynamic Activity Study of U-87 Human Glioma Cell with Photofrin (실험관 및 생체내에서 U-87 교모세포종 세포주의 광역학 치료 효과에 대한 연구)

  • Cho, Woo Jin;Cho, Kyung-Keun;Ji, Cheol;Park, Sung Chan;Park, Hea Kwan;Kang, Joon Ki;Choi, Chang Rak
    • Journal of Korean Neurosurgical Society
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    • v.30 no.5
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    • pp.553-560
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    • 2001
  • Objective : The objective of this study was to determine the photodynamic therapeutic response of U-87 human glioma cell in vitro as well as in the nude rat xenograft model using photofrin as photosensitizer. Material and Method : U-87 cells were cultured on 96-well culture plates, photofrin(Quadralogic Technologies Inc., Vancouver, Canada) was added into the cell culture medium at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$. 24 hour after drug treatment, cells were treated with optical(632nm) irradiation of $100mJ/cm^2$, $200mJ/cm^2$ and $400mJ/cm^2$. Photofrin(12.5mg/kg, i.p.) was administered to 28 nude rats containing intracerebral U-87 human glioma as well as 26 normal nude rats. 48 hours after administration, animals were treated with optical irradiation(632nm) of $35J/cm^2$, $140J/cm^2$ and $280J/cm^2$ to exposed tumor and normal brain. The photofrin concentration was measured in tumor and normal brain in a separate population of animals. Results : By MTT assay, there was 100% cytotoxicity at any dose of photofrin with optical irradiation of $200mJ/cm^2$ and $400mJ/cm^2$. But at the optical irradiation of $100mJ/cm^2$ cells were killed in dose dependent manner 28.5%, 49.1%, 54.4%, 78.2%, and 84.6% at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$, respectively. Dose dependent PDT lesions in both tumor and normal brain were observed. In the tumor lesion, only superficial tissue damage was found with optical irradiation of $35J/cm^2$. However, in the optical irradiation group of $140J/cm^2$ and $280J/cm^2$ the volume of lesions was measured of $7.2mm^3$ and $14.0mm^3$ for treatment at $140J/cm^2$ and $280J/cm^2$, respectively. The U-87 bearing rats showed a photofrin concentration in tumor tissue of $6.53{\pm}2.16{\mu}g/g$, 23 times higher than that found in the contralateral hemisphere of $0.28{\pm}0.15{\mu}g/g$. Conclusion : Our data indicate that the U-87 human glioma in vitro and in the xenografted rats is responsive to PDT. At these doses, a reproducible injury can be delivered to human glioma in this model. Strategies to spare the normal brain collateral damage are being studied.

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