Background and Purpose: Antimicrobial photodynamic therapy using Methylene blue (MB-PDT) has been proposed as an adjunctive to scaling and root planing (SRP) to provide preferable results for the treatment of periodontitis. The multi-factor mechanism of aPDT action correlates with various influencing components such as the photosensitizer and the light delivery system. The paper aims to review the recorded parameters of MB-PDT from clinical trials of periodontitis which may serve to improve the treatment of periodontal diseases. Materials and Methods: PubMed search engine was used to identify human clinical trials of PDT in dentistry. After applying specific keywords, additional filters, exclusion criteria, the initial number of 17378 was reduced to 12. Results: More than half of the articles of SRP + MB-PDT presented better results [pocket depth (PD) reduction, clinical attachment level (CAL) gain, etc.] compared to SRP alone in the treatment of periodontitis. Conclusions: While more clinical evidence is needed, recent studies demonstrate that MB-PDT combined with SRP show a greater potential as a treatment of periodontal diseases in comparison to SRP alone.

Photodynamic therapy (PDT) has been widely used in clinical fields and done by three components: photosensitizers (PSs), light and oxygen. Under the action of PS as an energy transforming media, the light energy is converted to chemical energy to make effects on target. In the process of PDT, its effect is determined a lot by the parameter of light and the characteristics of PSs. With the development of light source and photosensitizer, the application of PDT has been investigated in oral diseases. This review mainly focused on the effect of PDT on non-tumor diseases of oral cavity, including endodontic, periodontal and mucosal problem. Compared with the normal therapy, the combination therapy with PDT could obtain better efficacy. It was suggested that PDT showed great advantages as an adjuvant therapy in the above oral diseases. Through a further improvement, PDT is expected to play an increasingly important role on the oral disease treatment in the future.

Dental caries, the most common oral disease, is a multifactorial disease caused by interactions among bacteria within the dental plaque, food, and saliva, resulting in tooth destruction. Streptococcus mutans has been strongly implicated as the causative organism in dental caries and is frequently isolated from human dental plaque. Photodynamic therapy (PDT) is a technique that involves the activation of photosensitizer by light in the presence of tissue oxygen, resulting in the production of reactive radicals capable of inducing cell death. Postantibiotic effect (PAE) is defined as the duration of suppressed bacterial growth following brief exposure to an antibiotic. In this study, the in vitro PAE of PDT using erythrosine and light emitting diode on S. mutans ATCC 25175 was investigated. The PAE of PDT for 1 s irradiation and 3 s irradiation were 1.65 h and 2.1 h, respectively. The present study thus confirmed PAE of PDT using erythrosine on S. mutans.

Hilar cholangiocarcinoma is a fatal malignancy leading to high mortality rate despite recent therapeutic advances, and the photodynamic therapy has been noted as an emerging palliative strategy for the hilar cholangiocarcinoma. Photodynamic therapy is the treatment selectively destructing cancer tissue through the laser beam irradiation with particular wavelengths. Photosensitizer administered before the treatment is accumulated in malignant tissue, and activated in the limits of those wavelengths. The procedure is performed under percutaneous transhepatic biliary drainage or endoscopic retrograde cholangiopancreatography, and more appropriate for the periductal infiltrating type rather than mass-forming type of cholangiocarcinoma due to the shallow penetrating depth (<4.5 mm). Recent investigations demonstrated the survival gain of 4-6 months in patients with cholangiocarcinoma when it is added to palliative biliary drainage. In addition, newly developed 3rd generation photo sensitizer has enabled longer therapeutic effect with less skin phototoxicity than before. However, there are still some limitations should be concerned, including lack of large-scaled prospective studies, shallow penetrating depth of tumoricidal effects, lack of treatment response measure, and relatively expensive cost. Addressing these matters through the larger prospective studies or technical improvement may lead new era of photodynamic therapy not only for the palliative purpose but also in the therapeutic field of cholangiocarcinoma.

The purpose of this study was to assess the efficacy of photodynamic therapy (PDT) using erythrosine and a halogen light source to treat a biofilm formed on a machined surface titanium disk in vivo. Ten volunteers carried an acrylic appliance containing six machined surface titanium disks on the upper jaw over a period of five days. After the five days of biofilm formation period, the disks were removed. PDT using 20 μM erythrosine and halogen light was then applied to the biofilms formed on the disks. Experimental samples were divided into a negative control group (no erythrosine and no irradiation), E0 group (erythrosine 60s + no irradiation), E30 group (erythrosine 60s + halogen light 30s), and E60 group (erythrosine 60s + halogen light 60s). Following PDT, the bacteria in the biofilm were found to be detached from each disk. Each suspension with detached bacteria were diluted and cultivated on a blood-agar plate for five days under anaerobic conditions. The cultivated bacterial counts in the E60 group were significantly lower than the control group (86.4%) or E0 group (76.7%). In the experimental groups also, the light exposure time and bacterial counts showed a negative correlation. In conclusion, PDT using erythrosine and halogen light has bactericidal effects on biofilms formed on a titanium disk in vivo. Notably, applying 20 μM erythrosine and 60 seconds of halogen light irradiation had a significantly potent effect.

Photodynamic therapy(PDT) is recently developed as an effective treatment for malignant disease. Carboplatin, a less nephrotoxic analog of cisplatin, has been widely used for the treatment of multiple malignancies. In this study, we investigated the cytotoxic and apoptotic effect of combined modality of photofrin mediated PDT with cisplatin and carboplatin on KB cell human oral cancer cell line in vitro. The a ttached KB cells were incu bated with c isplatin(0.04mg/ml) and carboplatin(0.02mg/ml) for 24h at 37℃ and followed by photosensitization with photofrin for 6h and laser irradiation with 630nm LED at an intensity of 2.0 J/cm2 for activating photofrin for 15min. Then MTT assay and SYTO 16 green & Propidium iodide (PI) double staining were used respectively to measure the cytotoxicity and nuclear morphology at 24h after PDT. This study demonstrates that the combined modality with carbopaltin resulted in enhanced apoptotic cell death as well as cytotoxic e ffect on KB c ells in vitro, which s uggests the feasibility of combined modality and the possibility o f reducing the effective dosage of photofrin and carboplatin and lowering the side effects on normal cells

The organotypic raft culture model has been shown to be a useful method for examining the effects of biochemical manipulation on various epithelial cell types, using in vitro conditions that simulate the in vivo environment of the tissue of origin. To investigate this method as a model for photodynamic therapy (PDT), we cultures the oral squamous carcinoma cell line YD-10B on fibroblast-containing collagen gels at the air-liquid interface and assessed the efficacy of PDT using a photosensitiser 5-ALA-hexenyl ester. PDT effect on YD-10B organotypic raft cultures after twenty- four hours was determined. The number of residual cells was significantly reduced in comparison to control at all four different conditions. PCNA immunostaining and TUNEL assay revealed that PDT inhibited cell proliferation and increased apoptosis. These findings suggest that the organotypic raft culture model provides an effective and rapid laboratory method of investigating strategies for PDT on oral precancerous lesions and squamous cell carcinomas

PDT is an established cancer treatment modality. This can be attributed to the attractive basic concept of PDT; Combination of two therapeutic agents, a photosensitizing drug and light, which are relatively harmless by themselves but when combined, cause more or less selective tumor destruction. Hematoporphyrin-derived photosensitizers are known to be stable and highly efficient. In this study, we conducted a series of experiments to develop light-induced anticancer drugs against oral cancer cells. We tested the cytotoxicity of photodin by MTT assay and observed cell death pattern (apoptosis or necrosis) by hoechst 33342 and propidium iodide staining methods after PDT. IC50 value of photodin was 0.65 ug/ml. At higher doses of photodin ( > 7.8 ug/ml), cancer cells died exclusively from necrosis after PDT. By contrast, at IC50 value, photodin induced cancer cell to undergo apoptotic cell death. The induction begins approximately 6 hours after PDT. We investigated intracellular localization of photodin by oral cancer cell via confocal laser scanning microscopy. Oral cancer cells dual-stained with photodin and organelle-specific fluorescence probes (Mitotracker, Lysotracker, ER-Tracker) revealed that an intracellular fluorescence distribution was restricted to cytoplasmic compartments with no detectable fluorescence in the nucleus. Confocal images of cells containing photodin were overlapped with the mitochondria-specific fluorescence probe images of the same cells. These results demonstrated that photodin may play the role of a photosensitizer for oral squamous cancer cells without swelling and inflammation. Therefore, photodin-based PDT is a suitable treatment for oral cavity carcinoma patients.

We conducted a series of in vitro experiments to evaluate the anticancer effect of photodynamic therapy using hypericin and 532㎚ DPSS (diode pumped solid state laser). The cultured KB cells were treated with serial concentrations of hypericin ranging from 0.01㎍/㎖ to 5㎍/㎖ (two-fold dilution) with variable laser dosage (10J, 20J, 30J). The cell viability was evaluated by MTT assay. The type of cell death was detected by fluorescent microscope using Hoechst 33342 / PI (propidium iodide) stain methods. In this study, IC50 value with hypericin-mediated PDT with 10J DPSS laser was 35 ng/ml. The maximum cytotoxicity with Photofrin II-based PDT was observed at high drug concentrations(> 90 ng/ml) independent with laser dose. And the in vitro PDT effects depended on the laser dose and drug concentrations were displayed by the difference in the type of cell death, namely apoptosis or necrosis. According to this result, the hypericin based photodynamic therapy with DPSS laser was effective photodynamic therapy.

Photodynamic therapy(PDT) 는 특정 광 감응 물질 에 광 조사를 수행하여 세 포내애서 활성 산소종(ROS) 의 증가를 통한 암세 포의 사띨을 유도하는 방법이다 광 감응 물질은 암세 포에 선택 적으로 흡수되어 특정 파장의 빛을 홉수하여 다량의 ROS를 발생하여 암세 포의 사멸을 유도한다， 그러나 PDT 수행 시 ROS의 세 포내 작용에 따른 사띨 기전 이 영확히 알려지 지 않았고， 비 선 택 성으로 인한 정 상 세포애서의 피해 도 유발될 수 있다고 보고되었다 본 연 구애서 는 굉 감웅제인 He ma to por p h y rin을 이 용하여 구깅암 세포주인 He p2에서 광조사를 통한 세포 사멸 에 관한 연 구를 수행하였다 Confocal mi crosco py를 통한 분석에서 Hemato po r phyrin은 홉수 시 간에 따라 세포막에서 세 포질 핵 으로의 위치함을 관찰 할 수 있었고. 전기 영 동에 따른 DNA 분절 분석에서 24 시간이상 홉수된 상태 에서 ladder 패턴을 보임으로써 세 포 자띨사에 이 르는 만웅을 보였다 DCF - DA에 의힌 세 포내 ROS 분석 을 수행힌 결과 Hema to po rphyrin의 흡수 시간이 증가할수록 세포 내부에서의 ROS 발생이 증가함을 획 인 할 수 있었 다 이와 같은 결과에 따르면 Hematoporphyrin을 이용한 PDT에서 h ematoporphy ri n의 홉수 시 간에 따라 세 포 자띨사가 유도되었고. 특히 Hematoporphyrin은 흡수 시 간이 증가하여 세 포 내 부까지 충분히 Hematoporphyri n 이 작용된 경우에 서 ‘ ROS 발생애 따른 미 토콘드리아 의존적 경 로를 통해 세 포 자멸사가 유도되 었음을 확인 할 수 있었다-

Photodynamic therapy (PDT) is a clinically approved and ra pidly developing cancer treatment regimen, It is a minimally invasive procedure that requires the administration of a photosens iti zer foll owed by the illumination of the tumor with Iigh t of an appropriate wavelength, In the presence of molecular oxygen, cytotoxic intermedi a ries a re produced‘ thus damaging cellular structures containing the photosensitizer , In the present study. we exa mined the effectiveness of newly d evelped chlorin e6- induced PDT on malignant animal tumor model of 3prague-Da wley (3D) ra t Three-week-old male 3D rats we re inocula ted s ,c, on the right f1 ank with our previously esta blished k- ras-trans formed RK3E cell line (RK3E- ras. tota l, 5xl07 cell s) , The experiments were carried out 1 week after inoculation of tumor cell s , by which time the tumors had r eached about 0,7 mm to 1.0 cm in diameter, L3-chlorin e6 (L8 Pharm Co" Gwa ngju, Korea) was admin istrated intravenous ly by the tail vein of 3D rat at a dosage of 10 mg/kg after inhalation a nesthesia of ether, Twenty- four hours a fter L8-chlorin e6 ad ministration, PDT was pe rfol‘med using a laser diode (Geumgwang Co ‘ Ltd‘’ Daejeon, Korea) a t a light dose of 100 J /cm2 and wavelength of 664 nm, A..nimals were monitered daily and tumor volume was measured by calipel The tumor t reated with PDT using Ce6 had significant reduction in tumor s ize examined by gross tumor volume , softex x- ray image, molecular imaging a nalysis, respectively, PCNA immunostaining and TUNEL assay revealed that the treat ed tu mor caused signifi cant inlübition of tumor formati on with decreased tumor cell proliferation a nd increased a poptosis , Our dat a showed Ce6-induced PDT effecti vely arrested the tumor growth by inhibi t ing cell proliferation a nd inducing a poptosis , These findings provide the potential value of Ce6- induced PDT as an a lternative candidate for a nt i- tumor therapy, Furthel bi ochemical and cellular studies will reveal the precise molecul ar mecha ni sm of cell death induced by PDT

PDT is an established cancer treatment modality, This can be attri buted to the attractive basic concept of PDT; the combination 0 1' two therapeutic agents , a photosensiti zing drug and light, which are relatively harmless by themselves but combined ultimately cause more 0 1' less selective tumor destruction, The bacteri ochlorophyll - derivatived photosensitizer s are known to be s tabl e and highly effïcient, ln thí s study, we conducted a seríes of experiments to develope the light induced anticancer drugs against oral cancer cell , We tested the cytotoxi city of the hydroxybacteriochlorine by MTT assay and observed the cell death pattern(apoptosis or necrosis) after PDT by hoechst 33342 and propidium iodide s taining methods, lC50 value of the hydroxybac teriochlorine was 3 1 ， 3 ng/ n띠， At higher doses of hydroxybacteriochlori ne () 60ng/ rnQ) , cancer cells died exclus ively by necrosis after PDT By contrast, at lC50 value, hydroxybacteri ochlorine induced cancer cell to undergo apop totic c e ll death, The induct ion begins approximately 6 hours a fter PDT, We inves tigates intrace l1 ular localization of hydroxybacte riochlorine by oral cancel‘ cell via confocal laser scanning mi croscopy, Oral cancer cells dua l-stained with hydrox ybacteriochlo1' ine and organelle-specific flu orescence probes (Mi totracker , Lysotracke1', ER- Tracker) revealed an intracellular f1 uores c ence dis tribution restricted to cyt oplasmic compartments with no det ectable fluorescence in the nucleus, Confocal im ages of cells containing hydroxybacte1'iochl orine were never overla p to mitochondria, lysosome . endoplasmic reticulum when digita lly overla pped with tqe organel1e-specific f1 uorescence p1'obe images o{' the same cells These results demons trated tha t the hydroxybacte1' iochlorine may have a fun ction as a photosensitizer and cytotoxicity hydroxy bacteriochlo1'ine for o1'al cancer cell is more sensitive than head & neck cancer cell 0 1' ce1'vical cancer cell Therefore PDT using hydroxybacte1'iochl orine is suita ble treatment for oral cavity carcinoma patients

PDT is an establi shed cancer treatment modali ty , This can be attributed to the attractive basic concept of PDT; the combina ti on 0[' two ther a peut ic agents, a photosensitizing drug and light, which are r elatively harmless by themselves but combined ultimately ca use more 0 1' less selective tumor destruction, The bacteriochlorophyll - derivatived photosensitizers are known to be s ta ble and hi ghly efficient‘ In this s tudy, we conducted a series of experiments to develope the ligh t induced anticancer drugs against oral cancer cell ‘ We tested the cytotoxicity of the hydroxybact eriochlorine by MTT a ssay and observed the cell death pattern (apoptosis or necrosis) after PDT by hoechst 33342 and propidium iodide s taining methods , IC50 value of the hydroxybacteriochlorine was 31,3ngjm.Q, At higher doses of hydroxybacteriochlorine () 60 ng/ 뼈) ， cancer cells died exc lus ively by nec rosis after PDT By contrast, at IC50 value, h ydroxybacteri ochlorine in duced ca ncel' cell to undergo a poptotic cell death The induction begins approximately 6 hours after PDT We investigates int racellu la r localizati on of hydroxybact eri ochl orine by ora l cancer cell via confocal laser scanning microscopy, Oral can cer cells dual-stained with hydroxybactel' iochlorine and organelle-specific fluoresc ence probes (Mi totracker, Lysotracker , ER- Trac ker) revealed an int l'acellula l' flu orescence distribution restrict ed to cytoplasmic compartments with no detectable fl uoresce nce in the nucleus Confocal images of cells containing hydroxybacteriochlorine were never overlap to mi tochondria, lysosome, endoplasmic l'eticulum when digitally overlapped with the organelle-specific flu orescence probe images of the same cells , These resul ts demonstrat ed that the hydroxybacteriochlorine may have a function as a photosens it izer and cytotoxicity hydroxybactel' ioc hlorine for oral ca ncer cell is more sensitive than head & neck cancer cell or cervical cance l' cell Ther efore PDT using hydroxybact eriochlorine is suitable treatment for oral cavity car cinoma patients.

This study was conducted to test the anticancer effect of photodynamic therapy using chlorophyll derivative (9-HpbD-a) and 632nm diode laser. Human SNU 1041 cells were seeded into 96 well plate of 104cells/well and cultured for 24 hours. Cells were washed with media containing various concentration of 9-HpbD-a ranging from Oug/ml to 3.75ug/ml. Then 932 nm diode laser was given at various lasering time setting, and at various starting time after ini tial 24 hours of culture. The treated cells were incubated 48 hours and tetrazolium-based colorimetric(M'IT) assay was done to measure the viability of cells For in vivo study, SNU- 1041 cells were xenografted into the back of nude mouse. When the xenografted tumors grew up to 400-600 mm3, the animals were randomly placed into 4 groups: Group 1 (n=20) , PDT group, interstitial injection of 9-HpbD- a (47 ug/kg) followed by irradiation with 3.2 J/c야 of light 6 hours after then i띠 ection; Group II (n=lO) , irradiation with 3.2 J/crrf of light using diode laser; Group III (n=lO), in terstitial injection of 9-HpbD- a only(47 ug/kg); Group IV (n=lO), normal control group. The viability of cells was de creased with increasing lasering time No significant difference of cell viability was noted by variously delayed starting time of lasering. PDT effects were observed in the xenografted nude mouse model Group IV (no 9-HpbD-a, no laser irradiation) was a control group which showed a continuous tumor growth. Group III (9-HpbD-a i띠 ection only) showed no response, Group II (laser irradiation only) sho￦ed 1 complete remission out of 10 (10%) , Group 1 (9-HpbD-a and laser irradiation) showed 13 cpmplete remission out of 20 (65%) , Group 1 showed significant remission rate, comparing to other groups (p<0.05). This study demonstrated anticancer effect of photodynamic therapy using 9-HpbD-a and 632nm diode laser on human squamous cell carcinoma cell line.

We conducted a series of in vitro experiments to evaluate the efficiency of photodynamic therapy on head and neck cancer cell using hydroxybacteriochlorine from photosynthetic bacteria. We tested the cytotoxicity of the hydroxybacteriochlorine by MTI assay and observed the cell death pattern(apoptosis or necrosis) after PDT by hoechst 33342 and propidium iodide staining methods IC50 value of the hydroxybacteriochlorine was 0.22μg/rrúi. At higher doses of hydroxybacteriochlorine () 0.6μg/rrúi) , cancer cells died exclusively by necrosis after PDT. By contrast, at IC50 value, hydroxybacteriochlorine induced cancer cell to undergo apoptotic cell death. The induction begins approximately 6 hours after PDT. We investigates intracellular localization of hydroxybacteriochlorine by head & neck cancer cell via confocal laser scanning microscopy. Head & neck cancer cells dual-stained with hydroxybacteriochlorine and a panel of organelle- specific fluorescence probes (Mitotracker, Lysotracker, ER-Tracker) revealed an intracellular fluorescence distribution restricted to cytoplasmic compartments with no detectable fluorescence in the nucleus Confocal images of cells containing hydroxybacteriochlorine were never overlap in subcellular organelle fluorescence when digitally over layed with the organelle-specific fluorescence probe images of the same cells. These results demonstrated that the hydroxybacteriochlorine may have a function as a photosensitizer.

Photodynamic therapy is a non-invasive cancer therapy that has recently attracted much attention in the field of cancer treatment. This study is an experiment to observe the effect of laser dose difference in photodynamic therapy. Murine breast cancer cells, EMT6 cells, were used to generate tumor bearing mouse models. The experimental group was divided into 5 groups as control group, laser 100 J/cm2, 200 J/cm2, 300 J/cm2 and 400 J/cm2 irradiation group. Photofrin was administered intraperitoneally and after 48 hours, laser irradiated on tumor with energy 0-400 J/cm2. the tumor volume was measured with a digital caliper on day 0, day 2, day 4, day 8 and day 12. The volume of tumor after photodynamic therapy was increased in the control group, laser 100 J/cm2 irradiation group and laser 200 J/cm2 irradiation group until day 12 after irradiation. Both the laser 300 J/cm2 irradiated group and the laser 400 J/cm2 irradiated group showed a decrease in the tumor volume from 2 to 12 days after irradiation. These results suggested that treatment effect will be obtained at a dose of 300 J/cm2 or more in the experiment using the tumor bearing mouse model and photoprin.