Inactivation of pathogenic microorganisms by photodynamic techniques: Mechanistic aspects and perspective applications
Inactivation of pathogenic microorganisms by photodynamic techniques: Mechanistic aspects and perspective applications
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DOI：
10.2174/187152107780361652
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发表时间：
2007-04-01
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影响因子：
--
通讯作者：
Coppellotti, Olimpia
中科院分区：
文献类型：
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作者：
Jori, Giulio;Coppellotti, Olimpia
微生物对抗生素耐药性的全球性上升刺激了对替代治疗策略的开发的深入研究。光动力疗法（PDT）是一种治疗局部微生物感染的有前途的方法。对光敏剂的化学结构与其对微生物病原体的光毒性之间的关系的研究导致鉴定出具有最佳杀细胞效果的选定数量的化合物。这些包括吩噻嗪、卟啉和酞菁衍生物，它们的分子已被改造以引入以下特征：（a）存在阳离子部分，优选由于季铵化的氨基;（B）引入至少一个具有相对长烃链的N-烷基;（c）第（2）款对细胞培养的研究表明，PDT被赋予了有利的特性，抗微生物形式：（a）作用谱广，因为一种辐照方案可用于获得不同病原体组的灭活，例如处于营养和囊状阶段的革兰氏阳性和革兰氏阴性细菌、酵母菌、支原体和原生动物;（B）与微生物细胞的快速结合，这允许在短至5-10分钟的孵育时间后进行辐照，从而保证了与宿主组织相比的高选择性;（d）高的光灭活效率，因为在温和条件下通过照射可使微生物种群减少5-6个对数;（e）与给定病原体的抗药性谱无关的光敏活性;（f）第（1）款在重复治疗时缺乏对光抗性菌株的选择，并且诱导突变过程发生的风险最小。治疗慢性溃疡和选定的口腔感染。
The worldwide rise in antibiotic resistance by microorganisms has stimulated intensive research toward the development of alternative therapeutic strategies. Photodynamic therapy (PDT) is emerging as a promising modality for the treatment of localized microbial infections. Studies on the relationship between the chemical structure of photosensitising agents and their phototoxicity against microbial pathogens led to the identification of a selected number of compounds with optimal cytocidal effects. These include phenothiazine, porphyrin and phthalocyanine derivatives, whose molecule has been engineered to introduce the following features: (a) presence of cationic moieties, preferably due to quaternarized amino groups; (b) introduction of at least one N-alkyl group having a relatively long hydrocarbon chain; (c) overall amphiphilic character to promote the partitioning in the plasma membrane.Studies on cell cultures indicate that PDT is endowed with favourable properties to act as an antimicrobial modality: (a) broad spectrum of action, since one irradiation protocol can be used to obtain the inactivation of different groups of pathogens, such as Gram-positive and Gram-negative bacteria, yeasts, mycoplasmas and protozoa in both vegetative and cystic stages; (b) fast association with microbial cells, which allows irradiations to be performed after incubation times as short as 5-10 min., thereby guaranteeing a high selectivity as compared with host tissues; (d) high photoinactivation efficiency, since a 5-6 log decrease in microbial population is obtained by irradiation under mild conditions; (e) photosensitising activity independent of the antibiotic-resistance spectrum of the given pathogen; (f) lack of selection of photoresistant strains upon repeated treatment and minimal risk to induce the onset of mutagenic processes.Initial clinical trials involve the treatment of chronic ulcers and selected oral infections.