São Carlos Institute of Physics, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil.
Department of Chemistry, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro 22453-900, Brazil.
Proc Natl Acad Sci U S A. 2022 Jun 21;119(25):e2123564119. doi: 10.1073/pnas.2123564119. Epub 2022 Jun 13.
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 . 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.
在抗生素耐药感染（尤其是肺炎）迅速增加的背景下，抗菌光动力疗法（aPDT）作为一种有前途的治疗选择应运而生，因为诱导的损伤和由此导致的死亡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 在体外已经成功地应用于不同的细菌制剂，并且已经证明使用雾化和外部光激活进行肺递送的组合是可行的。然而，在获得足够的体内疗效结果方面进展甚微。本研究报告了肺表面活性剂作为肺部 aPDT 的重要抑制剂。在体外，临床用表面活性剂 Survanta®降低了吲哚菁绿、Photodithazine®、细菌叶绿素-trizma 和原卟啉 IX 对 的 aPDT 效应。吸收光谱、荧光光谱和光漂白曲线表明，疗效降低不是由于单线态氧猝灭所致，而分子动力学模拟表明其与表面活性剂磷脂的极性头基团具有亲和力，这可能会影响细菌对光敏剂的摄取。亚甲蓝是个例外，可能是因为其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。我们提出，在开发肺 aPDT 方案时，必须考虑肺表面活性剂与光敏剂之间的相互作用。
