Effect of Methylene Blue-mediated Photodynamic Therapy on Wild-type and Ciprofloxacin-resistant Mycobacterium smegmatis

Shim, Insoo,Choi, Myungwon,Min, Yegee,Seok, Kwang Hyuk,Kim, Jiyeun Kate,Jeong, Jee-Yeong,Oak, Chul-Ho,Park, Indal 대한미생물학회 2016 Journal of Bacteriology and Virology Vol.46 No.1

Tuberculosis (TB) patients are normally treated with a combination of antibiotics. However, with improper or incomplete treatment of antibiotics, the disease may progress to multidrug-resistant TB (MDR-TB). The treatment of MDR-TB is very costly and inefficient. Therefore, there is a great demand of new therapeutic approaches for MDR-TB such as photodynamic therapy. In this study, we tried to optimize the conditions for photodynamic inactivation of TB using methylene blue as a photosensitizer. Different combinations of methylene blue concentrations and light doses were tested for their photodynamic effects to A549 cells or Mycobacterium smegmatis (M. smegmatis). We also tested the effect of photodynamic therapy on ciprofloxacin-resistant M. smegmatis. Methylene blue treatment alone did not affect the survival rates of A549 cells or bacteria up to $5{\mu}g/ml$. When the A549 and M. smegmatis cells treated with methylene blue were irradiated with laser light (wavelength, 630 nm), photodynamic inactivation of cells was increased in methylene blue concentration- and light dose-dependent manners. Interestingly, the ciprofloxacin-resistant M. smegmatis exhibited higher level of susceptibility to methylene blue-mediated photodynamic inactivation. This study suggests that photodynamic therapy at $3.6J/cm^2$ in the presence of $5{\mu}g/ml$ methylene blue may be an appropriate range for therapy due to the high bactericidal activity against high level of ciprofloxacin-resistant M. smegmatis and the low damaging effect to mammalian cells. This study demonstrates that photodynamic therapy could be a potential alternative for MDR-TB treatment.

Chlorin e6 conjugated copper sulfide nanoparticles for photodynamic combined photothermal therapy

Bharathiraja, S.,Manivasagan, P.,Moorthy, M.S.,Bui, N.Q.,Lee, K.D.,Oh, J. ELSEVIER SCIENCE B.V., AMSTERDAM 2017 PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY Vol.19 No.-

The photo-based therapeutic approaches have attracted tremendous attention in recent years especially in treatment and management of tumors. Photodynamic and photothermal are two major therapeutic modalities which are being applied in clinical therapy. The development of nanomaterials for photodynamic combined with photothermal therapy has gained significant attention for its treatment efficacy. In the present study, we designed chlorin e6 (Ce6) conjugated copper sulfide (CuS) nanoparticles (CuS-Ce6 NPs) through amine functionalization and the synthesized nanoparticles act as a dual-model agent for photodynamic therapy and photothermal therapy. CuS-Ce6 NPs showed enhanced photodynamic effect through generation of singlet oxygen upon 670nm laser illumination. The same nanoparticles exerted thermal response under an 808nm laser at 2W/cm<SUP>2</SUP>. The fabricated nanoparticles did not show any cytotoxic effect toward breast cancer cells in the absence of light. In vitro cell viability assay showed a potent cytotoxicity in photothermal and photodynamic treatment. Rather than singular treatment, the photodynamic combined photothermal treatment showed an enhanced cytotoxic effect on treated cells. In addition, the CuS-Ce6 NPs exert a photoacoustic signal for non-invasive imaging of treated cells in tissue-mimicking phantom. In conclusion the CuS-Ce6 NPs act as multimodal agent for photo based imaging and therapy.

병적 근시와 동반된 맥락막 신생혈관에서 광역학 치료의 임상 적용

정은지,오현섭,고형준,이성철,권오웅.Eun-Jee Chung. M.D.. Hyun-Sub Oh. M.D.. Hyoung-Jun Koh. M.D.. Sung-Chul Lee. M.D.. Oh-Woong Kwon. M.D. 대한안과학회 2005 대한안과학회지 Vol.46 No.4

Purpose: To evaluate the effects of photodynamic therapy with verteporfin on visual acuity and fluorescein angiography in choroidal neovascularization (CNV) associated with pathologic myopia and to determine if this treatment could reproduce the results achieved in the Verteporfin in Photodynamic Therapy (VIP) Trial in Korean patients. Methods: Forty-two eyes of 39 patients with CNV secondary to pathologic myopia were included. A retrospective review of their clinical records and fluorescein angiography was done. The patients underwent photodynamic therapy with verteporfin and were followed up for more than 6 months after the therapy. The change in best corrected visual acuity (BCVA) and leakage in fluorescein angiography were evaluated. Results: The mean age of the patients was 39.6 and mean follow-up period was 23.5 months. The BCVA of the patients improved in 22 (52.4%) eyes, was unchanged in 13 (30.9%), and worsened in 7 (16.7%). The leakage in fluorescein angiography decreased in 25 (59.5%) eyes. Conclusions: Photodynamic therapy with verteporfin for myopic CNV in Korean patients appeared to be effective in stabilization of the lesions and improvement of visual acuity.

광역학요법을 이용한 치주염치료

모진아(Jin-A, Mo) 대한치과의사협회 2016 대한치과의사협회지 Vol.54 No.6

Objectives: Photodynamic therapy has been proven to promote additional clinical and microbiological benefits in the treatment of chronic periodontitis and aggressive periodontitis. The purpose of this study is to assess the effectiveness of the photodynamic therapy for patient with periodontitis. Methods: We searched the eight Korean databases and Ovid-MEDLINE, Ovid-EMBASE, Cochrane Library. Total 300 studies were searched and 13 studies were included in the final assessment. Each of the stages from literature search and extraction of data were carried out independently by 2 researchers. We used tools of Scottish Intercollegiate Guidelines Networks for assessment of the quality of studies. Results: The safety of the photodynamic therapy was assessed by bleeding. The effectiveness of the photodynamic therapy was assessed by the reduction of Probing pocket depth (PPD) and the gain of Clinical attachment level (CAL). The mean difference of PPD was 0.46(95% CI 0.09~0.82), (p=.01). ). The mean difference of CAL was ?0.49(95% CI ?1.12~0.14), (p=.13). Conclusion: The additional use of °∞Antimicrobial Photodynamic Therapy for Periodontitis°± caused hemorrhage to similar extents to conventional treatment modalities, where scaling and root planing are solely performed, in patients with periodontitis who are expected to have a lower degree of treatment response to non-surgical or surgical periodontal therapies (implant or refractory periodontitis) and those where there is a concern for the possible occurrence of antimicrobial side effects or resistance. This indicates that there are no problems with its safety. But there were no consistent reports about the effects of the additional use of photodynamic therapy. This led to a decision that the safety and efficacy of the current technology deserve further studies (Recommendation rating of A, Classification of technology II-a).

Photo-triggered photodynamic-photothermal combination cancer therapy with cancer detectable polysaccharide coated polydopamine nanoparticle

김지영,한지은,박우람,박신정,나건 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1

In these days, a sort of cancer remedy is photodynamic therapy (PDT) and it is widely used in clinical. Whereas, conventional photodynamic materials, photosensitizer (PS) showed high off-target side effect and photoactivation. To overcome drawbacks, we manufactured cancerspecific and photoactivity-controllable nanomedicine which is coated with cancer targeting polysaccharide-PS (PP) on polydopamine nanoparticle (PD-NP). Under cancer mimicking condition, the PP-NPs exhibited high singlet oxygen generation efficacy. Also, efficient photothermal conversion for photothermal therapy (PTT) was confirmed. In mouse tumor model, the photo-triggered PDT/PTT effect of the PP-NPs was much higher in cancer microenvironments than normal tissue. Consequently, the PP-NPs showed antitumor efficacy in mouse model and for efficient cancer treatment, nanoparticle photomedicine would be innovative strategy.

광역학치료와 베바시주맙을 이용한 특발 중심와부근 모세혈관확장증 I형의 치료

김인근(In Geun Kim),이지은(Ji Eun Lee),박정민(Jung Min Park) 대한안과학회 2016 대한안과학회지 Vol.57 No.12

목적: 중심와부근모세혈관확장증 type I으로 진단된 환자에서 베바시주맙 유리체강내 주입술과 광역학치료 병합요법의 효과에 대해 알아보았다. 대상과 방법: 2008년 5월부터 2012년 2월까지 시력저하를 주소로 내원한 환자 중 안저소견상 황반부 이측에 이상소견이 관찰되고 형광안저혈관조영술에서 모세혈관 확장으로 인한 누출이 관찰되어, 중심와부근모세혈관확장증 type I으로 진단된 7명을 대상으로 유리체강내 베바시주맙주사와 광역학 치료를 병행한 복합치료를 시행하였다. 결과: 시술 전 시력(logMAR)은 0.48 ± 0.14였고 시술 후 0.18 ± 0.17로 호전되었다. 안압은 시술 전 17.9 ± 3.1에서 16.8 ± 2.3으로 의미있는 차이를 보이지는 않았으며 시술 후 형광안저혈관조영술상에서 시술 전에 있었던 모세혈관 확장 부위 형광 누출이 감소되는 것을 관찰할 수 있었다. 빛간섭단층촬영에서 황반내 부종이 호전되어 central subfield macular thickness가 시술 전 301.9 ± 50.7 μm에서 시술 후 193.6 ± 58.8 μm로 감소하였다. 결론: 중심와부근모세혈관확장증 type I에서 망막하모세혈관확장과 황반부종으로 인해 시력저하가 생길 때 광역학치료와 베바시주맙유리체강내 주입술 병합 치료를 통해 단기간에 효과적인 병변 호전 및 시력 개선을 가져올 수 있었다. Purpose: We investigated the clinical manifestations of combination therapy with photodynamic therapy (PDT) and intravitreal bevacizumab in idiopathic macular telangiectasia type I patients. Methods: The present study included 7 patients who visited our clinic from May 2008 to February 2011 complaining of decreasing visual acuity and diagnosed as idiopathic macular telangiectasia type I including visible aneurysms at juxtafoveal area and telangiectatic vessels leakage based on fluorescein angiography. Additionally, all patients were treated with combination therapy with PDT and intravitreal bevacizumab. Results: Visual acuity improved from 0.48 ± 0.14 (log MAR) to 0.18 ± 0.17 (log MAR) after the combination therapy, however, there was no change in intraocular pressure between before (17.9 ± 3.1) and after (16.8 ± 2.3) therapy. After combination therapy, fluorescein angiography showed decreased leakage of telangiectatic vessels and optical coherence tomography showed only minimal intraretinal edema. Central subfield macular thickness decreased from 301.9 ± 50.7 μm to 193.6 ± 58.8 μm after the combination therapy. Conclusions: Combination therapy with intravitreal bevacizumab injection and PDT in patients with idiopathic macular telangiectasia type Ⅰ can result in a rapid decrease of macular edema, which can lead to rapid visual recovery.

Nanoparticle Platforms for Combined Photothermal and Photodynamic Therapy

박지호,Jeongmin Oh,Hwanjun Yoon 대한의용생체공학회 2013 Biomedical Engineering Letters (BMEL) Vol.3 No.2

Phototherapy is a promising strategy for cancer treatment due to its selective and localized therapeutic effect by laser irradiation. Photothermal therapy damages malignant cells by using heat converted from light by an agent. On the other hand, photodynamic therapy uses photosensitizers that become cytotoxic upon irradiation with laser light at excitation wavelength. As singular treatment of each phototherapy showed some limitations, there have been significant efforts to enhance therapeutic effect by combining photothermal and photodynamic therapy. Here we review recent developments of nanoparticle platforms, in which inorganic nanostructures (photothermal therapy) are integrated with photosensitizers (photodynamic therapy) for combined phototherapeutic effect.

Combination of Chemotherapy and Sonodynamic Therapy with Polylactide-poly (ethylene glycol) Polymersomes for Effective Cancer Treatments

Youngheun CHO,Taeho KIM,Hyuncheol KIM 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

In anticancer treatment, combination therapy is emerging to improve the insufficient anticancer efficacy off single therapies such as chemotherapy, photodynamic therapy (PDT), and sonodynamic therapy (SDT). Because free drugs are difficult to reach the target site due to degradation by enzymes in the body, drug delivery systems are being developed for combination therapy. However, nanocarriers such as microbubbles, albumin nanoparticles, and polymeric nanoparticles are unstable in the body and show low drug loading efficiency. Here, we propose polylactide (PLA)-poly (ethylene glycol) (PEG) polymersomes with a high drug loading rate for effective combination therapy. When irradiated with ultrasound, olymersomes with verteporfin and doxorubicin (VT-Dox-PLs), a sonosensitizer and a chemotherapeutic agent respectively, combination therapy efficacy was confirmed on MIA paca-2 cells. Also, through tumor volume change and in vivo bio distribution, VT-Dox-PLs showed the most effective anticancer efficacy. These results suggest that combination therapy of SDT and chemotherapy could show novel anticancer effect by VT-Dox-PLs.

증례 : 알레르기 ; 담도 유두종증에 대한 광역동치료 후 실내 생활에서 발생한 광과민반응 1예

박현우 ( Hyun Woo Park ),구본산 ( Bon San Koo ),배윤정 ( Yun Jeong Bae ),박도현 ( Do Hyun Park ),조유숙 ( You Sook Cho ),문희범 ( Hee Bom Moon ),김태범 ( Tae Bum Kim ) 대한내과학회 2010 대한내과학회지 Vol.79 No.1

광과민반응의 기왕력이 없는 담도 유두종증 환자에서 포르피머 투여와 광역동치료 시행 후 실내 생활만으로 얼굴 및 원위부 팔다리에 발생한 광과민반응 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Photodynamic therapy has been widely used in the treatment of various cancerous diseases. However, photodynamic therapy with a photosensitizer can cause a photosensitivity reaction on the skin. We report a case of a 64-year-old woman diagnosed with photosensitivity reaction after photodynamic therapy using the photosensitizer, porfimer. She presented to the emergency room with a skin rash on her face, neck, and both upper and lower extremities nine days after the photodynamic therapy. She denied any outdoor activity during that period. After administration of systemic corticosteroid and anti-histamine, her skin lesions resolved completely within seven days. (Korean J Med 79:92-95, 2010)

광역학적/광열치료 응용을 위한 광증감제가 결합한 골드 나노로드의 합성 및 특성분석

최종선 ( Jongseon Choi ),김소연 ( So Yeon Kim ) 한국공업화학회 2016 공업화학 Vol.27 No.6

최근 효과적인 암 치료 방법으로 광역학치료(photodynamic therapy)와 광열치료(photothermal therapy)가 주목받고 있다. 본 연구에서는 광열치료에 필요한 광열인자로써의 역할을 할 수 있는 골드 나노로드(AuNR)를 합성하고, 그 표면에 광역학 치료를 위한 광증감제(photosensitizer)를 결합하였다. 즉, 골드 나노로드를 체내에 오래 머무르도록 하기 위해 PEG(polyethylene glycol) 및 효과적인 암 표적지향성을 위해 FA (folic acid) 리간드를 도입하였고, FA-PEG와 poly-β-benzyl-L-aspartate (PBLA)로 이루어진 블록 공중합체를 3,4-dihydroxy hydrocinnamic acid (HCA) linker를 사용하여 골드나노로드의 표면개질을 하였다. 또한 AgNO₃의 feeding ratio 변화를 통해 다양한 aspect ratio를 갖는 골드 나노로드를 합성하였고, UV-visible spectrophotometer, ¹H-NMR, XPS, TEM 분석을 통해 FA-PEG-P(Asp)₅₀-HCA-AuNR100의 물리 화학적 특성과 morphology를 분석하였고, 성공적인 표면 개질을 확인할 수 있었다. 골드 나노로드의 표면 개질을 통한 생체 적합성 약물전달체의 합성은 효과적인 암 진단 및 다양한 광역학/광열치료 분야에 응용이 될 수 있을 것으로 기대된다. Recently, photodynamic and photothermal therapies have received increasing attention as an effective cancer treatment. In this study, a gold nanorod (AuNR) colloidal solution was synthesized as a hyperthermia agent for photothermal therapy and also modified with photosensitizer (PS) for photodynamic therapy. PEG (polyethylene glycol) and FA (folic acid) ligand were also introduced into AuNR for the long circulation in human body and efficient targeting of cancer cells, respectively and AuNRs were modified with FA-PEG and poly-β-benzyl-L-aspartate (PBLA) block copolymers through a 3,4-dihydroxy hydro-cinnamic acid (HCA) linker. A series of AuNRs with various aspect ratios were synthesized by controlling the feeding ratio of AgNO₃. The physicochemical property and morphology of synthesized AuNR100 and FA-PEG-P(Asp)₅₀-HCA-AuNR100 were analyzed by UV-visible spectrophotometer, ¹H NMR, XPS measurements, TEM. The surface modified AuNR carrier with biocompatibility could be applied for the effective diagnosis as well tumor phototherapy.