• Title/Summary/Keyword: photosensitizing agents

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Clinical development of photodynamic agents and therapeutic applications

  • Baskaran, Rengarajan;Lee, Junghan;Yang, Su-Geun
    • Biomaterials Research
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    • v.22 no.4
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    • pp.303-310
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    • 2018
  • Background: Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens and induces tumour regressions. Several photodynamic treatments have been extensively studied and the photosensitizers (PS) are key to their biological efficacy, while laser and oxygen allow to appropriate and flexible delivery for treatment of diseases. Introduction: In presence of oxygen and the specific light triggering, PS is activated from its ground state into an excited singlet state, generates reactive oxygen species (ROS) and induces apoptosis of cancer tissues. Those PS can be divided by its specific efficiency of ROS generation, absorption wavelength and chemical structure. Main body: Up to dates, several PS were approved for clinical applications or under clinical trials. $Photofrin^{(R)}$ is the first clinically approved photosensitizer for the treatment of cancer. The second generation of PS, Porfimer sodium ($Photofrin^{(R)}$), Temoporfin ($Foscan^{(R)}$), Motexafin lutetium, Palladium bacteriopheophorbide, $Purlytin^{(R)}$, Verteporfin ($Visudyne{(R)}$), Talaporfin ($Laserphyrin^{(R)}$) are clinically approved or under-clinical trials. Now, third generation of PS, which can dramatically improve cancer-targeting efficiency by chemical modification, nano-delivery system or antibody conjugation, are extensively studied for clinical development. Conclusion: Here, we discuss up-to-date information on FDA-approved photodynamic agents, the clinical benefits of these agents. However, PDT is still dearth for the treatment of diseases in specifically deep tissue cancer. Next generation PS will be addressed in the future for PDT. We also provide clinical unmet need for the design of new photosensitizers.

Possible Role of Nitric Oxide in Prevention of Atherosclerosis: Photo-induced adequate nitric oxide (PIANO)-mediated relaxation involves cyclic GMP increment (동맥경화 예방과 치료를 위한 연구시도: Nitric Oxide의 역활 -광 유도 nitric oxide(PIANO)의 혈관이완에 따른 cyclic GMP의 증가)

  • Chang, Ki-Churl;Chong, Won-Seog;Park, Byung-Wook;Lee, Seung-Youb;Ko, Hak-Joon
    • The Korean Journal of Pharmacology
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    • v.30 no.3
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    • pp.331-336
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    • 1994
  • Our purpose was to know whether photo-induced adequate nitric oxide (PIANO)-mediated relaxation of rat aorta is involved in cyclic GMP increment as well as inhibition of phosphatidylinositide hydrolysis due to phenylephrine (PE). Isometric tension was measured in vitro in response to either agents that modulate NO production or release NO by photolysis of photosensitizing agents in rat aorta that had been contracted with PE submaximally. PIANO-mediated relaxation was accompanied by increment of cyclic GMP, which was dependent on the intensity and duration of light exposure and concentration of photosensitizers. Phosphatidylinositide (PI) turnover augmented by PE was significantly inhibited by PIANO. These findings indiate that cGMP increment is responsible for PIANO-mediated relaxation and which may account for the inhibition of PI turnover due to ${\alpha}-adrenergic$ receptor stimulation.

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Photodynamic Therapy for Methicillin-resistant Staphylococcus aureus Using Various Photosensitizer

  • Kwon, Pil-Seung;Jo, Yoon-Kyung
    • Biomedical Science Letters
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    • v.15 no.3
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    • pp.233-239
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    • 2009
  • The aim of this study was to evaluate the photodynamic effect of various photosensitizing agents against methicillin-resistant Staphylococcus aureus (MRSA). MRSA was exposed to light from a 632 urn diode laser (15 J/$cm^2$) in the presence of various photosensitizer, such as photofrin, photogem, radachlorine and ALA. In vivo study was performed using ICR mice. Twenty eight mice had a standard wound ($100\;mm^2$) created on the dorsum, and MRSA was inoculated into the wound region. The four groups were classified as follows: (1) the untreated control group (bacteria alone), (2) the bacteria plus light group (15 J/$cm^2$), (3) the bacteria plus photofrin group (kept in the dark), and (4) the photodynamic therapy (PDT) group (bacteria, photofrin, and light). After photofrin (dose 1 mg/kg) injection, the experimental group was irradiated with 632 urn diode laser (15 J/$cm^2$) for 30 minutes after In vitro results of PDT showed the complete killing of MRSA at the photofrin, radachlorine, and photogem However, ALA-PDT was ineffective on MRSA viability. In vivo results showed that photofrin has therapeutic effect on the wound infection. These results demonstrate that selective lethal photosensitization of MRSA can be achieved using phofrin, photogem and radachlorin. Thus, PDT can inactivate MRSA survival.

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Gene Expression Profile of Lung Cancer Cells Following Photodynamic Therapy (폐암 세포주에서 광역학 치료에 의한 유전자 발현 분석)

  • Sung, Ji Hyun;Lee, Mi-Eun;Han, Seon-Sook;Lee, Seung-Joon;Ha, Kwon-Soo;Kim, Woo Jin
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.1
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    • pp.52-58
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    • 2007
  • Background: Photodynamic therapy is a viable option for lung cancer treatment, and many studies have shown that it is capable of inducing cell death in lung cancer cells. However, the precise mechanism of this cell death has not been fully elucidated. To investigate the early changes in cancer cell transcription, we treated A549 cells with the photosensitizer DH-I-180-3 and then we illuminated the cells. Methods: We investigated the gene expression profiles of the the A549 lung cancer cell line, using a DEG kit, following photodynamic therapy and we evaluated the cell viability by performing flow cytometry. We identified the genes that were significantly changed following photodynamic therapy by performing DNA sequencing. Results: The FACS data showed that the cell death of the lung cancer cells was mainly caused by necrosis. We found nine genes that were significantly changed and we identified eight of these genes. We evaluated the expression of two genes, 3-phosphoglycerate dehydrogenase and ribosomal protein S29. The expressed level of carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein and integrin beta 1 were decreased. Conclusion: Many of the gene products are membrane-associated proteins. The main mechanism of photodynamic therapy with using the photosensitizing agent DH-I-180-3 appears to be necrosis and this may be associated with the altered production of membrane proteins.

Benzochloroporphyrin Derivative Induced Cytotoxicity and Inhibition of Tumor Recurrence During Photodynamic Therapy for Osteosarcoma

  • Gong, Hai-Yang;Sun, Meng-Xiong;Hu, Shuo;Tao, Ying-Ying;Gao, Bo;Li, Guo-Dong;Cai, Zheng-Dong;Yao, Jian-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3351-3355
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    • 2013
  • Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dosedependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.

Effects of adjunctive daily phototherapy on chronic periodontitis: a randomized single-blind controlled trial

  • Jung, Gyu-Un;Kim, Jin-Woo;Kim, Sun-Jong;Pang, Eun-Kyoung
    • Journal of Periodontal and Implant Science
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    • v.44 no.6
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    • pp.280-287
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    • 2014
  • Purpose: The purpose of this randomized single-blind controlled trial was to elucidate the clinical and antimicrobial effects of daily phototherapy (PT) as an adjunct to scaling and root planing (SRP) in patients with chronic periodontitis. Methods: The study was conducted from December 2013 to May 2014 at Ewha Womans University Mokdong Hospital, Seoul, Korea. Forty-one patients with mild to moderate chronic periodontitis were randomly divided into two therapeutic groups in a 1:1 ratio: SRP+PT and SRP (control) groups. All participants underwent full-mouth SRP. PT was performed thrice a day for a month by using electric toothbrushes with embedded light-emitting diodes. Plaque index, gingival index, probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing were assessed before (baseline) and four weeks after (follow-up) the treatment. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Parvimonas micra, Campylobacter rectus, Eikenella corrodens, Streptococcus mutans, and Streptococcus sobrinus levels were detected by a real-time polymerase chain reaction at the same points in time. Results: The clinical parameters improved in both the groups. At the follow-up assessment, PPD was significantly decreased in the SRP+PT group (P=0.00). Further, PPD and CAL showed significantly greater changes in the SRP+PT group than in the SRP group (PPD, P=0.03; CAL, P=0.04). P. gingivalis and T. forsythia levels decreased in this group, but no significant intergroup differences were noted. Conclusions: Adjunctive PT seems to have clinical benefits, but evidence of its antimicrobial effects is not sufficient. Long-term studies are necessary to develop the most effective PT protocol and compare the effectiveness of PT with and without exogenous photosensitizers.

Effect of Photodynamic Therapy in Lung Cancer (폐암에서 광역동치료술의 효과)

  • Yoon, Sung Ho;Han, Kyung Taek;Kim, Gyung Nam;Lee, Seung Il
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.4
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    • pp.358-363
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    • 2004
  • Background : Photodynamic therapy (PDT) involves the use of photosensitizing agents for treatment of malignant disease. PDT is approved by the U.S. Food and Drug Administration for the endobronchial microinvasive nonsmall cell lung cancer and for palliation in patients with obstructing tumors. We report our experience and results of PDT in lung cancer. Method : Ten patients with lung cancer who were diagnosed in Chosun university hospital by histologic confirm through bronchoscopy were included between August 2002 and May 2003. The photosensitizer (Photogem$^{(R)}$, Lomonosov institute of Fine Chemical, Russia/dose 2.0 mg/kg body weight) was injected 48 hours prior to the PDT session. For PDT with the photosensitizer (Photogem$^{(R)}$), Diode LASER system (Biolitec Inc., Germany, wavelength; 633nm) were used. PDTs were done at 48-72 hours after photogem injection. Follow up bronchoscopy and chest X-ray or thorax computerized tomography were done for evaluate PDT response. Results : 9 of 10 patients with endobronchial obstruction showed partial remission with bronchus opening after PDT. Direct reaction of the tumor to PDT was similar in despite of its localization. It was as follows; edema, hyperemia, in-situ bleeding, fibrin film occurrence. Any other complications such as sunburns of skin, inflammation within the PDT zone were not occurred by the end of the fourth week. Conclusion : In the advanced endobronchial disease, PDT has been shown to be useful in treating endobronchial tumors that are causing clinically significant dyspnea or are likely to progress and lead to further clinical complications, such as postobstructive pneumonia.

Optimum Treatment Parameters for Photodynamic Antimicrobial Chemotherapy on Streptococcus mutans Biofilms (Streptococcus mutans biofilm에 대한 광역동 치료의 최적조건에 관한 연구)

  • Choi, Seojung;Park, Howon;Lee, Juhyun;Seo, Hyunwoo;Lee, Siyoung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.42 no.2
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    • pp.151-157
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    • 2015
  • The purpose of this study was to evaluate the effects of Photochemotherapy using a combination of erythrosine and standard halogen dental curing lights on the viability of Streptococcus mutans in the biofilm phase. To investigate the optimum treatment parameters, the researchers controlled the concentration of erythrosine, light irradiation time and the treatment time of erythrosine. The higher concentration of erythrosine (0, 10, 20, 40, 80 M) in the presence of light irradiation created greater effects in reducing the viability of S. mutans. The results showed a statistically significant difference among the antimicrobial effects in 20, 40, 80 M erythrosine. The higher irradiation time of light (0, 5, 15, 30, 60, 75s) in the presence of erythrosine showed greater effects in reducing the viability of S. mutans. There was statistically significant difference in 30, 60, 75 seconds. The higher treatment time of erythrosine (0, 1, 2.5, 5min) in the presence of erythrosine created greater effects on reduction of S. mutans viability. Statistically significant differences were found between 2.5 and 5 minutes of erythrosine treatment time. The results of this study showed that the photochemotherapy on S. mutans using erythrosine and the halogen dental curing lights conventionally used in dental clinics is effective in the condition of 20-40 M erythrosine concentration, irradiation time over 30 seconds, and erythrosine treatment time over 2.5 minutes.