Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum-Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, Italy.
Molecules. 2023 Mar 3;28(5):2348. doi: 10.3390/molecules28052348.
Chlorin e6 (Ce6) is among the most used sensitizers in photodynamic (PDT) and sonodynamic (SDT) therapy; its low solubility in water, however, hampers its clinical exploitation. Ce6 has a strong tendency to aggregate in physiological environments, reducing its performance as a photo/sono-sensitizer, as well as yielding poor pharmacokinetic and pharmacodynamic properties. The interaction of Ce6 with human serum albumin (HSA) (i) governs its biodistribution and (ii) can be used to improve its water solubility by encapsulation. Here, using ensemble docking and microsecond molecular dynamics simulations, we identified the two Ce6 binding pockets in HSA, i.e., the Sudlow I site and the heme binding pocket, providing an atomistic description of the binding. Comparing the photophysical and photosensitizing properties of Ce6@HSA with respect to the same properties regarding the free Ce6, it was observed that (i) a red-shift occurred in both the absorption and emission spectra, (ii) a maintaining of the fluorescence quantum yield and an increase of the excited state lifetime was detected, and (iii) a switch from the type II to the type I mechanism in a reactive oxygen species (ROS) production, upon irradiation, took place.
叶绿素 e6（Ce6）是光动力疗法（PDT）和声动力疗法（SDT）中最常用的敏化剂之一；然而，其在水中的低溶解度阻碍了其临床应用。Ce6 在生理环境中具有强烈的聚集倾向，降低了其作为光/声敏化剂的性能，并导致较差的药代动力学和药效学特性。Ce6 与人血清白蛋白（HSA）的相互作用（i）控制其生物分布，（ii）可以通过封装来提高其水溶性。在这里，我们使用整体对接和微秒分子动力学模拟，确定了 HSA 中 Ce6 的两个结合口袋，即 Sudlow I 位点和血红素结合口袋，提供了结合的原子描述。将 Ce6@HSA 的光物理和光致敏化性质与游离 Ce6 的相同性质进行比较，观察到（i）吸收和发射光谱均发生红移，（ii）荧光量子产率保持不变，激发态寿命增加，以及（iii）在辐照时，ROS 产生的从 II 型到 I 型机制的转变。
