Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Phys Chem Chem Phys. 2020 Jun 4;22(21):12228-12238. doi: 10.1039/d0cp01755h.
Light activated photosensitizers generate reactive oxygen species (ROS) that interfere with cellular components and can induce cell death, e.g., in photodynamic therapy (PDT). The effect of cellular components and especially proteins on the photochemistry and photophysics of the sensitizers is a key aspect in drug design and the correlating cellular response with the generation of specific ROS species. Here, we show the complex range of effects of binding of photosensitizer to a multidrug resistance protein, produced by bacteria, on the formers reactivity. We show that recruitment of drug like molecules by LmrR (Lactococcal multidrug resistance Regulator) modifies their photophysical properties and their capacity to induce oxidative stress especially in 1O2 generation, including rose bengal (RB), protoporphyrin IX (PpIX), bodipy, eosin Y (EY), riboflavin (RBF), and rhodamine 6G (Rh6G). The range of neutral and charged dyes with different exited redox potentials, are broadly representative of the dyes used in PDT.
光激活的光敏剂会产生活性氧（ROS），这些 ROS 会干扰细胞成分，并可能导致细胞死亡，例如在光动力疗法（PDT）中。细胞成分，尤其是蛋白质对光敏剂的光化学和光物理性质的影响是药物设计的一个关键方面，也是与特定 ROS 种类的产生相关的细胞反应的关键方面。在这里，我们展示了结合到由细菌产生的多药耐药蛋白上的光敏剂的复杂的一系列作用，这些作用会改变其反应性。我们表明，LmrR（乳球菌多药耐药调节剂）招募类似药物的分子会改变它们的光物理性质，以及它们诱导氧化应激的能力，特别是在 1O2 的生成方面，包括孟加拉玫瑰红（RB）、原卟啉 IX（PpIX）、bodipy、曙红 Y（EY）、核黄素（RBF）和罗丹明 6G（Rh6G）。具有不同激发氧化还原电位的中性和带电染料的范围广泛地代表了 PDT 中使用的染料。
