Small size gold nanoparticles enhance apoptosis-induced by cold atmospheric plasma via depletion of intracellular GSH and modification of oxidative stress

Small size gold nanoparticles enhance apoptosis-induced by cold atmospheric plasma via depletion of intracellular GSH and modification of oxidative stress
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DOI:
10.1038/s41420-020-00314-x
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发表时间:
2020-09-10
影响因子:
7
通讯作者:
Kondo, Takashi
Kondo, Takashi
中科院分区:
医学2区
文献类型:
--
作者:
Jawaid, Paras;Rehman, Mati Ur;Kondo, Takashi

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金纳米颗粒(Au-NPs)因其高原子序数(Z)而作为一种有前途的敏化剂而引起人们的关注,并且由于它们被认为是完全多功能的,因此它们比其他金属纳米颗粒更受欢迎。冷大气等离子体(CAP)最近也受到关注,特别是用于癌症治疗,通过形成活性氧(ROS)诱导细胞凋亡。在这项研究中,不同大小的金纳米粒子与氦基CAP(He-CAP)的活性进行了分析,并探讨了潜在的机制。仅用小Au-NP(2nm)处理细胞显著增强He-CAP诱导的细胞凋亡。相比之下,40 nm和100 nm Au-NP未能增强细胞死亡。从机制上讲,协同增强是由于2 nm Au-NPs诱导的细胞内谷胱甘肽减少,导致细胞内ROS的产生。He-CAP在水介质中显著诱导ROS产生;然而,单独用He-CAP处理不诱导细胞内ROS形成。与此相反,联合处理显着增加细胞内的超氧阴离子(O-2(中心点))和羟基自由基((OH)-O-中心点)的形成。这些发现表明Au-NPs与CAP组合的潜在治疗用途,并进一步阐明Au-NPs在He-CAP辅助治疗中的作用。
Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O-2(center dot -)) and hydroxyl radical ((OH)-O-center dot). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.