In the context of the rapid increase of antibiotic-resistant infections, in particular of pneumonia, antimicrobial photodynamic therapy (aPDT), the microbiological application of photodynamic therapy (PDT), comes in as a promising treatment alternative since the induced damage and resultant death are not dependent on a specific biomolecule or cellular pathway. The applicability of aPDT using the photosensitizer indocyanine green with infrared light has been successfully demonstrated for different bacterial agents in vitro, and the combination of pulmonary delivery using nebulization and external light activation has been shown to be feasible. However, there has been little progress in obtaining sufficient in vivo efficacy results. This study reports the lung surfactant as a significant suppressor of aPDT in the lungs. In vitro, the clinical surfactant Survanta® reduced the aPDT effect of indocyanine green, Photodithazine®, bacteriochlorin-trizma, and protoporphyrin IX against Streptococcus pneumoniae. The absorbance and fluorescence spectra, as well as the photobleaching profile, suggested that the decrease in efficacy is not a result of singlet oxygen quenching, while a molecular dynamics simulation showed an affinity for the polar head groups of the surfactant phospholipids that likely impacts uptake of the photosensitizers by the bacteria. Methylene blue is the exception, likely because its high water solubility confers a higher mobility when interacting with the surfactant layer. We propose that the interaction between lung surfactant and photosensitizer must be taken into account when developing pulmonary aPDT protocols.

中文翻译：

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肺表面活性剂对细菌的光动力失活产生负面影响-体外和分子动力学模拟分析。

在抗生素耐药性感染迅速增加的背景下，特别是肺炎，抗菌光动力疗法 (aPDT)，光动力疗法 (PDT) 的微生物学应用，作为一种有前途的治疗替代方案出现，因为诱导的损伤和由此产生的死亡是不依赖于特定的生物分子或细胞途径。使用光敏剂吲哚菁绿和红外光的 aPDT 的适用性已在体外针对不同的细菌制剂成功证明，并且使用雾化和外部光激活的肺部递送的组合已被证明是可行的。然而，在获得足够的体内疗效结果方面进展甚微。该研究报告肺表面活性物质是肺中 aPDT 的重要抑制剂。体外，临床表面活性剂 Survanta® 降低了吲哚菁绿、Photodithazine®、菌绿素-trizma 和原卟啉 IX 对肺炎链球菌的 aPDT 作用。吸光度和荧光光谱以及光漂白曲线表明，功效的降低不是单线态氧猝灭的结果，而分子动力学模拟显示了对表面活性剂磷脂的极性头基的亲和力，这可能会影响吸收细菌产生的光敏剂。亚甲蓝是个例外，可能是因为它的高水溶性使其在与表面活性剂层相互作用时具有更高的流动性。我们建议在制定肺 aPDT 方案时必须考虑肺表面活性物质和光敏剂之间的相互作用。