Smijs Threes G M, van der Haas Richard N S, Lugtenburg Johan, Liu Yan, de Jong Rob L P, Schuitmaker Hans J
Department of Ophthamology, Leiden University Medical Centre, 2333 AL Leiden, The Netherlands.
Photochem Photobiol. 2004 Sep-Oct;80(2):197-202. doi: 10.1562/2004-04-22-RA-146.
The application of photosensitizers for the treatment of fungal infections is a new and promising development within the field of photodynamic treatment (PDT). Dermatophytes, fungi that can cause infections of the skin, hair and nails, are able to feed on keratin. Superficial mycoses are probably the most prevalent of infectious diseases in all parts of the world. One of the most important restrictions of the current therapeutic options is the return of the infection and the duration of the treatment. This is especially true in the case of infections of the nail (tinea unguium) caused by Trichophyton rubrum, an anthropophilic dermatophyte with a worldwide distribution. Recently, we demonstrated that 5,10,15-tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and deuteroporphyrin monomethylester were excellent photosensitizers toward T. rubrum when using broadband white light. This study demonstrates the photodynamic activity of these photosensitizers with red light toward both a suspension culture of T. rubrum and its isolated microconidia. The higher penetration depth of red light is important for the PDT of nail infections. In addition, we tested the photodynamic activity of a newly synthesized porphyrin, quinolino-[4,5,6,7-efg]-7-demethyl-8-deethylmesoporphyrin dimethylester, displaying a distinct peak in the red part of the spectrum. However, its photodynamic activity with red light toward a suspension culture of T. rubrum appeared to be only fungistatic. Sylsens B was the best photosensitizer toward both T. rubrum and its microconidia. A complete inactivation of the fungal spores and destruction of the fungal hyphae was found. In studies into the photostability, Sylsens B appeared to be photostable under the conditions used for fungal PDT. A promising result of this study is the demonstration of the complete degradation of the fungal hyphae in the time after the PDT and the inactivation of fungal spores, both with red light. These results offer the ingredients for a future treatment of fungal infections, including those of the nail.
光敏剂在真菌感染治疗中的应用是光动力治疗(PDT)领域一项新的且有前景的进展。皮肤癣菌是一类可引起皮肤、毛发和指甲感染的真菌,能够以角蛋白为食。浅表真菌病可能是世界上所有地区最普遍的传染病。当前治疗方案最重要的限制之一是感染复发和治疗持续时间。对于由红色毛癣菌引起的指甲感染(甲癣)来说尤其如此,红色毛癣菌是一种嗜人皮肤癣菌,在全球范围内均有分布。最近,我们证明了5,10,15 - 三(4 - 甲基吡啶鎓)- 20 - 苯基 - [21H,23H] - 卟吩三氯化物(Sylsens B)和去氢卟啉单甲酯在使用宽带白光时对红色毛癣菌是优异的光敏剂。本研究证明了这些光敏剂在红光照射下对红色毛癣菌悬浮培养物及其分离出的微分生孢子均具有光动力活性。红光较高的穿透深度对于指甲感染的光动力治疗很重要。此外,我们测试了一种新合成的卟啉喹啉 - [4,5,6,7 - efg] - 7 - 去甲基 - 8 - 去乙基中卟啉二甲酯的光动力活性,其在光谱的红色部分有一个明显的峰值。然而,它在红光照射下对红色毛癣菌悬浮培养物的光动力活性似乎只是抑菌性的。Sylsens B是对红色毛癣菌及其微分生孢子最好的光敏剂。发现真菌孢子完全失活且真菌菌丝被破坏。在光稳定性研究中,Sylsens B在用于真菌光动力治疗的条件下似乎是光稳定的。这项研究一个有前景的结果是证明了在光动力治疗后,红光可使真菌菌丝完全降解以及真菌孢子失活。这些结果为未来真菌感染(包括指甲感染)的治疗提供了要素。