Rybkin Alexander Yu, Kurmaz Svetlana V, Urakova Elizaveta A, Filatova Natalia V, Sizov Lev R, Kozlov Alexey V, Koifman Mikhail O, Goryachev Nikolai S
Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Pr. Akademika Semenova 1, 142432 Chernogolovka, Russia.
Faculty of Fundamental Physical and Chemical Engineering, Lomonosov Moscow State University, 119991 Moscow, Russia.
Pharmaceutics. 2023 Jan 12;15(1):273. doi: 10.3390/pharmaceutics15010273.
A series of nanoparticles (NPs) with a hydrodynamic radius from 20 to 100 nm in PBS was developed over the solubilization of hydrophobic dye methyl pheophorbide (chlorin e derivative) by amphiphilic copolymers of N-vinylpyrrolidone with (di)methacrylates. Photophysical properties and biological activity of the NPs aqueous solution were studied. It was found that the dye encapsulated in the copolymers is in an aggregated state. However, its aggregation degree decreases sharply, and singlet oxygen quantum yield and the fluorescence signal increase upon the interaction of these NPs with model biological membranes-liposomes or components of a tissue homogenate. The phototoxic effect of NPs in HeLa cells exceeds by 1.5-2 times that of the reference dye chlorin e trisodium salt-one of the most effective photosensitizers used in clinical practice. It could be explained by the effective release of the hydrophobic photosensitizer from the NPs into biological structures. The demonstrated approach can be used not only for the encapsulation of hydrophobic photosensitizers for PDT but also for other drugs, and -vinylpyrrolidone amphiphilic copolymers show promising potential as a modern platform for the design of targeted delivery vehicles.
通过 N - 乙烯基吡咯烷酮与（二）甲基丙烯酸酯的两亲共聚物增溶疏水性染料甲基脱镁叶绿酸（二氢卟吩 e 衍生物），制备了一系列在 PBS 中流体动力学半径为 20 至 100 nm 的纳米颗粒（NPs）。研究了 NPs 水溶液的光物理性质和生物活性。发现包裹在共聚物中的染料处于聚集状态。然而，当这些 NPs 与模型生物膜 -脂质体或组织匀浆成分相互作用时，其聚集程度急剧降低，单线态氧量子产率和荧光信号增加。NPs 对 HeLa 细胞的光毒性作用比临床实践中最有效的光敏剂之一参考染料二氢卟吩 e 三钠盐高 1.5 - 2 倍。这可以通过疏水性光敏剂从 NPs 有效释放到生物结构中来解释。所展示的方法不仅可用于封装用于光动力疗法（PDT）的疏水性光敏剂，还可用于其他药物，并且 N - 乙烯基吡咯烷酮两亲共聚物作为设计靶向递送载体的现代平台显示出有前景的潜力。
