M.V. Lomonosov Moscow State University, Department of Chemistry, GSP-1, Leninskie gory 1, build. 3, Moscow, 119991, Russia.
M.V. Lomonosov Moscow State University, Department of Physics, GSP-1, Leninskie gory 1, build. 2, Moscow, 119991, Russia.
Sci Rep. 2017 Jun 13;7(1):3410. doi: 10.1038/s41598-017-03527-w.
The overproduction of hydrogen peroxide is an inherent feature of some tumour cells and inflamed tissues. We took advantage of this peculiarity to eliminate cells using chemiluminescent peroxyoxalate reaction. We designed dispersions containing polyoxalate and tetramethylhematoporhyrin (TMHP) in dimethylphthalate droplets stabilized with Pluronic L64. The porphyrin plays the dual role. On the one hand, it serves as an activator of the peroxyoxalate reaction of polyoxalate with intracellular hydrogen peroxide and experiences excitation as a result of the reaction. The light emitted in the reaction in the model system without cells was used to optimize the dispersion's composition. On the other hand, TMHP acts as a photosensitizer (PS) causing cell damage. The formation of singlet oxygen led to cell elimination if the dispersions were used in combination with inducers of oxidative stress: hydrogen peroxide, paraquat, antitumour drug doxorubicin, or a nutritional additive menadione. The PS-induced cytotoxicity correlated with the level of intracellular ROS. The developed approach targeted to endogenous ROS is orthogonal to the classical chemotherapy and can be applied to increase its efficiency.
过氧化氢的过度产生是一些肿瘤细胞和炎症组织的固有特征。我们利用这一特性，通过化学发光过氧草酸酯反应来消除细胞。我们设计了含有多聚草酸酯和四甲基血卟啉（TMHP）的分散体，在二甲苯酸二甲酯液滴中用 Pluronic L64 稳定。卟啉具有双重作用。一方面，它作为多聚草酸酯与细胞内过氧化氢的过氧草酸酯反应的激活剂，并因反应而经历激发。在没有细胞的模型系统中的反应中发出的光被用于优化分散体的组成。另一方面，TMHP 作为光敏剂（PS）导致细胞损伤。如果将分散体与氧化应激诱导剂（过氧化氢、百草枯、抗癌药物阿霉素或营养添加剂维生素 K3）一起使用，形成单线态氧会导致细胞消除。PS 诱导的细胞毒性与细胞内 ROS 水平相关。开发的针对内源性 ROS 的方法与经典化疗正交，可以应用于提高其效率。
