MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory of Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Molecules. 2023 Jun 8;28(12):4639. doi: 10.3390/molecules28124639.
Photodynamic therapy (PDT) is recognized as a powerful method to inactivate cells. However, the photosensitizer (PS), a key component of PDT, has suffered from undesired photobleaching. Photobleaching reduces reactive oxygen species (ROS) yields, leading to the compromise of and even the loss of the photodynamic effect of the PS. Therefore, much effort has been devoted to minimizing photobleaching in order to ensure that there is no loss of photodynamic efficacy. Here, we report that a type of PS aggregate showed neither photobleaching nor photodynamic action. Upon direct contact with bacteria, the PS aggregate was found to fall apart into PS monomers and thus possessed photodynamic inactivation against bacteria. Interestingly, the disassembly of the bound PS aggregate in the presence of bacteria was intensified by illumination, generating more PS monomers and leading to an enhanced antibacterial photodynamic effect. This demonstrated that on a bacterial surface, the PS aggregate photo-inactivated bacteria via PS monomer during irradiation, where the photodynamic efficiency was retained without photobleaching. Further mechanistic studies showed that PS monomers disrupted bacterial membranes and affected the expression of genes related to cell wall synthesis, bacterial membrane integrity, and oxidative stress. The results obtained here are applicable to other types of PSs in PDT.
光动力疗法(PDT)被认为是一种有效的细胞灭活方法。然而,光动力疗法的关键组成部分——光敏剂(PS),存在着不理想的光漂白现象。光漂白会降低活性氧(ROS)的产生,从而降低 PS 的光动力效应,甚至导致其丧失。因此,人们致力于最大限度地减少光漂白,以确保光动力疗效不会损失。在这里,我们报告了一种 PS 聚集体,它既没有光漂白也没有光动力作用。当直接与细菌接触时,PS 聚集体被发现会分解成 PS 单体,从而对细菌具有光动力灭活作用。有趣的是,在光照下,结合态 PS 聚集体在细菌存在的情况下的解离加剧,产生更多的 PS 单体,从而增强了抗菌光动力效应。这表明在细菌表面,PS 聚集体在照射过程中通过 PS 单体来光灭活细菌,而光动力效率在没有光漂白的情况下得以保留。进一步的机制研究表明,PS 单体破坏了细菌的细胞膜,并影响了与细胞壁合成、细胞膜完整性和氧化应激相关的基因的表达。这里获得的结果适用于 PDT 中的其他类型的 PS。