Photodynamic Low Level Laser Squamous Cell Carcinoma

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Photodynamic Low Level Laser Squamous Cell Carcinoma ( photodynamic-low-level-laser-squamous-cell-carcinoma )

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Int. J. Mol. Sci. 2018, 19, 1107 2 of 17 field. The authors concluded that PDT with porfimer sodium is an effective treatment for these indications [8]. PDT as possible treatment modality in high risk dysplasia, intraepithelial neoplasia, and T1 SCC of the larynx was investigated in a single institution, Phase-Ib study on pyropheophorbide (HPPH)-PDT. In this study, 29 subjects and 30 lesions were treated. Patients with T1 SCC had a complete response rate of 82%. The most common adverse event was transient hoarseness. Two patients required tracheostomy because of laryngeal edema [9]. 1.1. Mechanisms of PDT and Common Photosensitizer Photodynamic therapy (PDT) requires three components, the photosensitizer, oxygen, and light source [4]. The basic principle of PDT is energy transfer from the photosensitizer to oxygen in the tissue under light excitation. Under light excitation, reactive oxygen species, especially singlet oxygen, are generated which cause cellular toxicity. Selective uptake of the photosensitizer in premalignant or malignant cells is the clue to specificity of PDT [10]. Repeatability is an important feature of PDT, furthermore PDT has no accumulative destructive effect and does not negatively influence further treatment like radiation or chemotherapy [7]. A variety of photosensitizers are available [11,12]. 5-aminolevulinic acid hydrochloride (5-ALA) is a porphyrin, which gets metabolized in the target tissue to the proper photosensitizer. The porphyrin 5-ALA accumulates selectively in tumor tissues and is rapidly eliminated from the human body. It is routinely used for PDT treatment of actinic keratosis [13]. Another common photosensitizer is mTHPC, a lipophilic chlorin of the second generation, which has a high tumor selectivity and a high yield of reactive oxygen species [11,14,15]. 1.2. Methylene Blue as A Photosensitizer Methylene blue (MB), also known as methylthioninium chloride, is a hydrophilic phenothiazine derivative. It is a photosensitizer with light absorption at 660 nm [16]. This maximum lies well within the emission range of common diode lasers used for low level laser therapy. These lasers are frequently at hand at institutions treating head & neck cancer patients or are available at low cost [17]. Environmental light does barely activate MB. Therefore, adverse effects due to environmental light exposure are not to be expected. Moreover, MB is an inexpensive photosensitizer. MB is used for antimicrobial photodynamic therapy (APDT) and is used as a potent PDT drug for local treatment of periodontal diseases [15], because of its efficiency against a broad spectrum of microbes including bacteria, fungi, and viruses [18,19]. The efficiency of MB-APDT has also been demonstrated on an antibiotic resistant polymicrobial biofilms of Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) in a maxillary sinus model. An in vitro maxillary sinus biofilm study demonstrated that APDT reduced the polymicrobial biofilm in chronic rhinosinusitis by >99.99% after a single treatment [20]. Different MB concentration and exposure times were reported. Betsy and coworker assessed 90 patients with untreated chronic periodontitis for scaling and root planning and APDT or scaling and root planning alone. The photosensitizer used consisted of MB suspended in double distilled water at a concentration of 10 mg/mL. As light source a diode laser operating at 655 nm was used [21]. MB concentrations used in clinical studies ranged from 100 μg/mL [22] to 10 μg/mL [23]. A Brazilian study group proved PDT in pediatric dentistry. APDT was performed using methylene blue (50 μg/mL) as photosensitizer for 5 min as pre irradiation time and after the red laser was delivered [24]. Another Brazilian study group used PDT with methylene blue for onychomycosis. MB 2% aqueous solution was applied to the lesion until saturation occurred, followed by a rest period of 3 min. The MB solution was not washed off. After the rest period, the lesion was immediately illuminated with noncoherent red light (630 nm) [25]. Early reports suggest that tumor selectivity of MB is low. Direct application of MB on the tumor site may result in accumulation within tumor cells. In analogy to toluidine blue, this effect is probably due to impaired epithelial barrier at the tumor site. In order to improve tumor cell selectivity, MB has been targeted specifically to tumor cells. Therefore, MB was embedded into a nanoparticle carrying tumor antibodies or tumor-specific peptides [26–28].

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